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Sample records for rapid antidepressant effects

  1. Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

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    Wenda Xue

    2013-01-01

    Full Text Available The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2, leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression.

  2. Methoxetamine produces rapid and sustained antidepressant effects probably via glutamatergic and serotonergic mechanisms.

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    Botanas, Chrislean Jun; Bryan de la Peña, June; Custodio, Raly James; Joy Dela Peña, Irene; Kim, Mikyung; Woo, Taeseon; Kim, Hee Jin; Kim, Hye In; Chang Cho, Min; Lee, Yong Sup; Cheong, Jae Hoon

    2017-11-01

    Depression afflicts around 16% of the world's population, making it one of the leading causes of disease burden worldwide. Despite a number of antidepressants available today, the delayed onset time and low remission rate of these treatments are still a major challenge. The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has shown to produce rapid and sustained antidepressant effects and has paved the way for a new generation of glutamate-based antidepressants. Methoxetamine (MXE) is a ketamine analogue that acts as an NMDA receptor antagonist and a serotonin reuptake inhibitor. However, no studies have evaluated the antidepressant effects of MXE. Here, we assessed whether MXE produces antidepressant effects and explored possible mechanisms underlying its effects. Mice were treated with MXE (2.5, 5, or 10 mg/kg) and their behavior was evaluated 30 min and 24 h later in an array of behavioral experiments used for screening antidepressant drugs. A separate group of mice were treated with NBQX, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, or ketanserin, a 5HT2 receptor antagonist, before MXE (5 mg/kg) administration in the forced swimming test (FST). We also investigated the effect of MXE on glutamatergic- and serotonergic-related genes in the mouse hippocampus using quantitative real-time PCR. MXE produced antidepressant effects 30 min after treatment that persisted for 24 h. Both NBQX and ketanserin blocked the antidepressant effects of MXE in the FST. MXE also altered hippocampal glutamatergic- and serotonergic gene expressions. These results suggest that MXE has rapid and sustained antidepressant effects, possibly mediated by the glutamatergic and serotonergic system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Transiently increased glutamate cycling in rat PFC is associated with rapid onset of antidepressant-like effects

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    Chowdhury, Golam M.I.; Zhang, Jie; Thomas, Monique; Banasr, Mounira; Ma, Xiaoxian; Pittman, Brian; Bristow, Linda; Schaeffer, Eric; Duman, Ronald; Rothman, Douglas; Behar, Kevin; Sanacora, Gerard

    2016-01-01

    Several drugs have recently been reported to induce rapid antidepressant effects in clinical trials and rodent models. Although the cellular mechanisms involved remain unclear, reports suggest that increased glutamate transmission contributes to these effects. Here, we demonstrate that the antidepressant-like efficacy of three unique drugs, with reported rapid onset antidepressant properties, is coupled with a rapid transient rise in glutamate cycling in medial prefronal cortex (mPFC) of awak...

  4. Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade

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    Elena eNosyreva

    2014-12-01

    Full Text Available Ketamine is a NMDA receptor antagonist that produces rapid antidepressant responses in individuals with major depressive disorder. The antidepressant action of ketamine has been linked to blocking NMDA receptor activation at rest, which inhibits eukaryotic elongation factor2 kinase leading to desuppression of protein synthesis and synaptic potentiation in the CA1 region of the hippocampus. Here, we investigated ketamine mediated antidepressant response and the resulting synaptic potentiation in juvenile animals. We found that ketamine did not produce an antidepressant response in juvenile animals in the novelty suppressed feeding or the forced swim test. In addition ketamine application failed to trigger synaptic potentiation in hippocampal slices obtained from juvenile animals, unlike its action in slices from older animals (6-9 weeks old. The inability of ketamine to trigger an antidepressant response or subsequent synaptic plasticity processes suggests a developmental component to ketamine mediated antidepressant efficacy. We also show that the NMDAR antagonist AP5 triggers synaptic potentiation in mature hippocampus similar to the action of ketamine, demonstrating that global competitive blockade of NMDA receptors is sufficient to trigger this effect. These findings suggest that global blockade of NMDA receptors in developmentally mature hippocampal synapses are required for the antidepressant efficacy of ketamine.

  5. Rapid antidepressant effects of Yueju: A new look at the function and mechanism of an old herbal medicine.

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    Ren, Li; Chen, Gang

    2017-05-05

    Yueju is a traditional herbal medicine which consists of five herbs and formulated to treat depression-related syndromes 800 years ago. Yueju is still widely prescribed to treat conditions which include digestive dysfunction and depression. Recently, Yueju has been shown to promote a fast-onset antidepressant effect clinically and in preclinical studies. Because conventional antidepressants have a delayed onset in treating depression, the novelty of Yueju's rapid antidepressant effect and its underlying mechanism are of great significance both clinically and scientifically. To review the use of Yueju for treatment of mood-related syndromes, and particularly its use in depression. To evaluate recent evidence of Yueju rapid antidepressant actions, based on new findings at behavioral and molecular levels. To suggest direction for future studies to address further scientific issues. Reports regarding to the history and current use of Yueju are summarized. Recent progress on rapid antidepressant effects of Yueju, the crucial constituent, Gardenia jasminoides J.Ellis (GJ) and other herbs, are reviewed. The medical need for rapid antidepressant actions, as well as breakthrough findings using ketamine and its limitations are introduced. Studies with Yueju using a number of acute, subacute and chronic behavioral paradigms are compared with ketamine. Findings from clinical reports also support the rapid action of Yueju. Studies examine the contribution of the constituent herb GJ, in rapid antidepressant effects. Importantly, research into the mechanism of Yueju or GJ's antidepressant response indicate the importance of up-regulation in the neural circuit responsible for antidepressant activity, and highlight common and specific molecular signaling by Yueju that may explain why this herb formula has unique antidepressant activity. Preclinical and clinical studies demonstrate that Yueju confers rapid antidepressant effects. The common mechanisms shared both for ketamine and

  6. R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

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    Yang, C; Shirayama, Y; Zhang, J-c; Ren, Q; Yao, W; Ma, M; Dong, C; Hashimoto, K

    2015-01-01

    Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)–TrkB signaling, and synaptogenesis in selected brain regions. In the social defeat stress and learned helplessness models of depression, R-ketamine showed a greater potency and longer-lasting antidepressant effect than S-ketamine (esketamine). Furthermore, R-ketamine induced a more potent beneficial effect on decreased dendritic spine density, BDNF–TrkB signaling and synaptogenesis in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of the hippocampus from depressed mice compared with S-ketamine. However, neither stereoisomer affected these alterations in the nucleus accumbens of depressed mice. In behavioral tests for side effects, S-ketamine, but not R-ketamine, precipitated behavioral abnormalities, such as hyperlocomotion, prepulse inhibition deficits and rewarding effects. In addition, a single dose of S-ketamine, but not R-ketamine, caused a loss of parvalbumin (PV)-positive cells in the prelimbic region of the medial PFC and DG. These findings suggest that, unlike S-ketamine, R-ketamine can elicit a sustained antidepressant effect, mediated by increased BDNF–TrkB signaling and synaptogenesis in the PFC, DG and CA3. R-ketamine appears to be a potent, long-lasting and safe antidepressant, relative to S-ketamine, as R-ketamine appears to be free of psychotomimetic side effects and abuse liability. PMID:26327690

  7. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine

  8. The role of adipokines in the rapid antidepressant effects of ketamine.

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    Machado-Vieira, R; Gold, P W; Luckenbaugh, D A; Ballard, E D; Richards, E M; Henter, I D; De Sousa, R T; Niciu, M J; Yuan, P; Zarate, C A

    2017-01-01

    We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key adipokines-adiponectin, resistin and leptin-as potential predictors of response to ketamine or as possible transducers of its therapeutic effects. Eighty treatment-resistant subjects who met DSM-IV criteria for either major depressive disorder (MDD) or bipolar disorder I/II and who were currently experiencing a major depressive episode received a single ketamine infusion (0.5 mg kg(-1) for 40 min). Plasma adipokine levels were measured at three time points (pre-infusion baseline, 230 min post infusion and day 1 post infusion). Overall improvement and response were assessed using percent change from baseline on the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. Lower baseline levels of adiponectin significantly predicted ketamine's antidepressant efficacy, suggesting an adverse metabolic state. Because adiponectin significantly improves insulin sensitivity and has potent anti-inflammatory effects, this finding suggests that specific systemic abnormalities might predict positive response to ketamine. A ketamine-induced decrease in resistin was also observed; because resistin is a potent pro-inflammatory compound, this decrease suggests that ketamine's anti-inflammatory effects may be transduced, in part, by its impact on resistin. Overall, the findings suggest that adipokines may either predict response to ketamine or have a role in its possible therapeutic effects.

  9. Antidepressants: Can They Lose Effectiveness?

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    ... t seem to be having the same effect. Can antidepressants lose effectiveness? Answers from Daniel K. Hall- ... some people and not in others. There also can be other reasons an antidepressant is no longer ...

  10. Mechanisms of rapid antidepressant effects of sleep deprivation therapy: clock genes and circadian rhythms.

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    Bunney, Blynn G; Bunney, William E

    2013-06-15

    A significant subset of both major depressive disorder and bipolar disorder patients rapidly (within 24 hours) and robustly improves with the chronotherapeutic intervention of sleep deprivation therapy (SDT). Major mood disorder patients are reported to have abnormal circadian rhythms including temperature, hormonal secretion, mood, and particularly sleep. These rhythms are modulated by the clock gene machinery and its products. It is hypothesized that SDT resets abnormal clock gene machinery, that relapse of depressive symptoms during recovery night sleep reactivates abnormal clock gene machinery, and that supplemental chronotherapies and medications can block relapse and help stabilize circadian-related improvement. The central circadian clock genes, BMAL1/CLOCK (NPAS2), bind to Enhancer Boxes to initiate the transcription of circadian genes, including the period genes (per1, per2, per3). It is suggested that a defect in BMAL1/CLOCK (NPAS2) or in the Enhancer Box binding contributes to altered circadian function associated, in part, with the period genes. The fact that chronotherapies, including SDT and sleep phase advance, are dramatically effective suggests that altered clock gene machinery may represent a core pathophysiological defect in a subset of mood disorder patients. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants

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    Caroline Ann Browne

    2013-12-01

    Full Text Available Newer antidepressants are needed for the many individuals with major depressive disorder that do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent evidence from clinical trials shows that the NMDA antagonist ketamine is a revolutionary novel antidepressant because it acts rapidly and is effective for treatment-resistant patients. A single infusion of ketamine alleviates depressive symptoms in treatment-resistant depressed patients within hours and these effects may be sustained for up to 2 weeks. Although the discovery of ketamine’s effects has reshaped drug discovery for antidepressants, the psychotomimetic properties of this compound limit the use of this therapy to the most severely ill patients. In order to develop additional antidepressants like ketamine, adequate preclinical behavioral screening paradigms for fast-acting antidepressants need to be established and used to identify the underlying neural mechanisms. This review examines the preclinical literature attempting to model the antidepressant-like effects of ketamine. Acute administration of ketamine has produced effects in behavioral screens for antidepressants like the forced swim test, novelty suppression of feeding and in rodent models for depression. Protracted behavioral effects of ketamine have been reported to appear after a single treatment that last for days. This temporal pattern is similar to its clinical effects and may serve as a new animal paradigm for rapid antidepressant effects in humans. In addition, protracted changes in molecules mediating synaptic plasticity have been implicated in mediating the antidepressant-like behavioral effects of ketamine. Current preclinical studies are examining compounds with more specific pharmacological effects at glutamate receptors and synapses in order to develop additional rapidly acting antidepressants without the hallucinogenic side effects or abuse

  12. Optogenetic stimulation of infralimbic PFC reproduces ketamine's rapid and sustained antidepressant actions.

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    Fuchikami, Manabu; Thomas, Alexandra; Liu, Rongjian; Wohleb, Eric S; Land, Benjamin B; DiLeone, Ralph J; Aghajanian, George K; Duman, Ronald S

    2015-06-30

    Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely blocked the antidepressant and anxiolytic effects of systemic ketamine in rodent models and that ketamine microinfusion into IL-PFC reproduced these behavioral actions of systemic ketamine. We also found that optogenetic stimulation of the IL-PFC produced rapid and long-lasting antidepressant and anxiolytic effects and that these effects are associated with increased number and function of spine synapses of layer V pyramidal neurons. The results demonstrate that ketamine infusions or optogenetic stimulation of IL-PFC are sufficient to produce long-lasting antidepressant behavioral and synaptic responses similar to the effects of systemic ketamine administration.

  13. The Requirement of L-Type Voltage-Dependent Calcium Channel (L-VDCC) in the Rapid-Acting Antidepressant-Like Effects of Scopolamine in Mice.

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    Yu, Hanjie; Li, Mengmeng; Shen, Xinbei; Lv, Dan; Sun, Xin; Wang, Jinting; Gu, Xinmei; Hu, Jingning; Wang, Chuang

    2018-02-01

    Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium channels were found to mediate rapid-acting antidepressant effects of certain medications (e.g., ketamine). Therefore, it is of great interest to determine the involvement of L-type voltage-dependent calcium channels in the action of scopolamine. Herein, we investigated the mechanisms underlying behavioral responses to various doses of scopolamine in mice to clarify the involvement of L-type voltage-dependent calcium channels in its modes of action. Open field test, novel object recognition test, and forced swimming test were performed on mice administered varied doses of scopolamine (0.025, 0.05, 0.1, 1, and 3 mg/kg, i.p.) alone or combined with L-type voltage-dependent calcium channel blocker verapamil (5 mg/kg, i.p.). Then, the changes in brain-derived neurotrophic factor and neuropeptide VGF (nonacronymic) levels in the hippocampus and prefrontal cortex of these mice were analyzed. Low doses of scopolamine (0.025 and 0.05 mg/kg) produced significant antidepressant-like effects in the forced swimming test, while higher doses (1 and 3 mg/kg) resulted in significant memory deficits and depressive-like behaviors. Moreover, the behavioral changes in responses to various doses may be related to the upregulation (0.025 and 0.05 mg/kg) and downregulation (1 and 3 mg/kg) of brain-derived neurotrophic factor and VGF in the hippocampus and prefrontal cortex in mice. We further found that the rapid-acting antidepressant-like effects and the upregulation on brain-derived neurotrophic factor and VGF produced by a low dose of scopolamine (0.025 mg/kg) were completely blocked by verapamil. These results indicate that L-type voltage-dependent calcium channels are likely involved in the behavioral

  14. Neuroimmune endocrine effects of antidepressants

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    Antonioli M

    2012-02-01

    Full Text Available Marco Antonioli, Joanna Rybka, LA CarvalhoPsychoimmunology Translational Laboratory, Health Science Research Centre, Roehampton University, London, UKAbstract: Antidepressant pharmacotherapy is to date the most often used treatment for depression, but the exact mechanism of action underlying its therapeutic effect is still unclear. Many theories have been put forward to account for depression, as well as antidepressant activity, but none of them is exhaustive. Neuroimmune endocrine impairment is found in depressed patients; high levels of circulating corticosteroids along with hyperactivation of the immune system, high levels of proinflammatory cytokines, low levels of melatonin in plasma and urine, and disentrainment of circadian rhythms have been demonstrated. Moreover, antidepressant treatment seems to correct or at least to interfere with these alterations. In this review, we summarize the complex neuroimmune endocrine and chronobiological alterations found in patients with depression and how these systems interact with each other. We also explain how antidepressant therapy can modify these systems, along with some possible mechanisms of action shown in animal and human models.Keywords: antidepressant agents, biological markers, human, cytokines, neuroinflammation, psychoneuroimmunology, endophenotype

  15. Effects of antidepressant treatment following myocardial infarction

    NARCIS (Netherlands)

    Van Melle, Joost P.; De Jonge, Peter; Honig, Adriaan; Schene, Aart H.; Kuyper, Astrid M. G.; Crijns, Harry J. G. M.; Schins, Annique; Tulner, Dorien; Van den Berg, Maarten P.; Ormel, Johan

    Background Depression following myocardial infarction is associated with poor cardiac prognosis. It is unclear whether antidepressant treatment improves long-term depression status and cardiac prognosis. Aims To evaluate the effects of antidepressant treatment compared with usual care in an

  16. Effects of antidepressant treatment following myocardial infarction

    NARCIS (Netherlands)

    van Melle, Joost P.; de Jonge, Peter; Honig, Adriaan; Schene, Aart H.; Kuyper, Astrid M. G.; Crijns, Harry J. G. M.; Schins, Annique; Tulner, Dorien; van den Berg, Maarten P.; Ormel, Johan

    2007-01-01

    BACKGROUND: Depression following myocardial infarction is associated with poor cardiac prognosis. It is unclear whether antidepressant treatment improves long-term depression status and cardiac prognosis. AIMS: To evaluate the effects of antidepressant treatment compared with usual care in an

  17. Rapid onset of antidepressant action: a new paradigm in the research and treatment of major depressive disorder.

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    Machado-Vieira, Rodrigo; Salvadore, Giacomo; Luckenbaugh, David A; Manji, Husseini K; Zarate, Carlos A

    2008-06-01

    Current therapeutics of depression are similar in their time to antidepressant action and often take weeks to months to achieve response and remission, which commonly results in considerable morbidity and disruption in personal, professional, family, and social life, as well as risk for suicidal behavior. Thus, treatment strategies presenting a rapid improvement of depressive symptoms--within hours or even a few days--and whose effects are sustained would have an enormous impact on public health. This article reviews the published data related to different aspects of rapid improvement of depressive symptoms. Literature for this review was obtained through a search of the MEDLINE database (1966-2007) using the following keywords and phrases: rapid response, antidepressant, time to, glutamate, sleep, therapeutics, latency, and depression. The data obtained were organized according to the following topics: clinical relevance and time course of antidepressant action, interventions showing evidence of rapid response and its potential neurobiological basis, and new technologies for better understanding rapid anti-depressant actions. A limited number of prospective studies evaluating rapid antidepressant actions have been conducted. Currently, only a few interventions have been shown to produce antidepressant response in hours or a few days. The neurobiological basis of these rapid antidepressant actions is only now being deciphered. Certain experimental treatments can produce antidepressant response in a much shorter period of time than existing medications. Understanding the molecular basis of these experimental interventions is likely to lead to the development of improved therapeutics rather than simply furthering our knowledge of current standard antidepressants.

  18. Rapid-onset antidepressant efficacy of glutamatergic system modulators: the neural plasticity hypothesis of depression.

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    Wang, Jing; Jing, Liang; Toledo-Salas, Juan-Carlos; Xu, Lin

    2015-02-01

    Depression is a devastating psychiatric disorder widely attributed to deficient monoaminergic signaling in the central nervous system. However, most clinical antidepressants enhance monoaminergic neurotransmission with little delay but require 4-8 weeks to reach therapeutic efficacy, a paradox suggesting that the monoaminergic hypothesis of depression is an oversimplification. In contrast to the antidepressants targeting the monoaminergic system, a single dose of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine produces rapid (within 2 h) and sustained (over 7 days) antidepressant efficacy in treatment-resistant patients. Glutamatergic transmission mediated by NMDARs is critical for experience-dependent synaptic plasticity and learning, processes that can be modified indirectly by the monoaminergic system. To better understand the mechanisms of action of the new antidepressants like ketamine, we review and compare the monoaminergic and glutamatergic antidepressants, with emphasis on neural plasticity. The pathogenesis of depression may involve maladaptive neural plasticity in glutamatergic circuits that may serve as a new class of targets to produce rapid antidepressant effects.

  19. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.

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    Linge, Raquel; Jiménez-Sánchez, Laura; Campa, Leticia; Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Pazos, Angel; Adell, Albert; Díaz, Álvaro

    2016-04-01

    Cannabidiol (CBD), the main non-psychotomimetic component of marihuana, exhibits anxiolytic-like properties in many behavioural tests, although its potential for treating major depression has been poorly explored. Moreover, the mechanism of action of CBD remains unclear. Herein, we have evaluated the effects of CBD following acute and chronic administration in the olfactory bulbectomy mouse model of depression (OBX), and investigated the underlying mechanism. For this purpose, we conducted behavioural (open field and sucrose preference tests) and neurochemical (microdialysis and autoradiography of 5-HT1A receptor functionality) studies following treatment with CBD. We also assayed the pharmacological antagonism of the effects of CBD to dissect out the mechanism of action. Our results demonstrate that CBD exerts fast and maintained antidepressant-like effects as evidenced by the reversal of the OBX-induced hyperactivity and anhedonia. In vivo microdialysis revealed that the administration of CBD significantly enhanced serotonin and glutamate levels in vmPFCx in a different manner depending on the emotional state and the duration of the treatment. The potentiating effect upon neurotransmitters levels occurring immediately after the first injection of CBD might underlie the fast antidepressant-like actions in OBX mice. Both antidepressant-like effect and enhanced cortical 5-HT/glutamate neurotransmission induced by CBD were prevented by 5-HT1A receptor blockade. Moreover, adaptive changes in pre- and post-synaptic 5-HT1A receptor functionality were also found after chronic CBD. In conclusion, our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signalling through a 5-HT1A receptor-dependent mechanism. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. [Long-term clinical effects of antidepressive agents].

    Science.gov (United States)

    Sechter, D

    1995-03-01

    According to long term studies with antidepressants versus placebo, the therapeutic efficacy is prolonged: a long term treatment in full dosage seems to reduce from almost half the risk of relapse and recurrence till five years, during recurrent major affective disorders. We should therefore be cautious and we should not have a systematic prescription for all types of depressions; antidepressants are efficacious but have side effects and we do not know well their abilities in long term use. During bipolar disorders the prescription of long term antidepressants, even in association with normothymics, does not give benefits and can induce rapid cycles. In dysthymias and depressions with personality disorders, a psychotherapy is indicated, and it is difficult to evaluate the efficacy of a long term antidepressant treatment. Tricyclics antidepressants, MAOI's and SSRI's have classical side effects, and they can also induce: modifications of the symptomatology, of cognitive functions, of sleep, eating and sexual behaviours; modifications of the course of depressive illness, induction of manic switches, and may be sometimes an exacerbation of suicidal ideation ... pharmacogenetic modifications with their action on hepatic metabolism, neuroendocrine alterations and long term effects on monoamines. We have also to take into account the long term treatment consequences on quality of life, on self esteem with the importance of psychodynamic and relationships modifications. The use of a long term antidepressant treatment should be adapted to each individual, being cautious of its potential benefits and risks.

  1. The effects of antidepressants on gastric ulcer

    Directory of Open Access Journals (Sweden)

    Mehmet Latif Güneş

    2013-12-01

    Full Text Available In their daily practice, psychiatrists often experience gastriccomplaints in patients beside psychiatric disorders.Peptic ulcer is one of the diseases, which accompanyto psychiatric disorders including mainly depression. Itis shown that antidepressants can inflame the bleedingsincluding gastrointestinal (GI bleedings, while they havepositive effect on ulcer healing. In this review, studies,which conducted about the positive or negative effects ofantidepressant drugs on ulcer treatment were examined.Accordingly; it was found that opipramol, amitriptyline,imipramine that of tricyclic antidepressants was found tobe helpful in healing of the ulcer. It was stated that SelectiveSerotonin Reuptake Inhibitors generally inflamedulcers, exceptionally fluvoxamine and fluoxetine reducedulcer; moclobemide that of monoamine-oxidase inhibitorand tianeptine and mirtazapine that of atypical antidepressantshad positive effect in ulcer healing. To be carefulin choosing the appropriate antidepressant in psychiatricpatients with gastric ulcer is important in the prognosisof both ulcer and depression.Key words: peptic ulcer; depression; antidepressant drugs

  2. Neurobiology of stress, depression, and rapid acting antidepressants: remodeling synaptic connections.

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    Duman, Ronald S

    2014-04-01

    Stress and depression are associated with atrophy and loss of neurons in limbic and cortical brain regions that could contribute to the symptoms of depression. Typical monoamine reuptake inhibitor antidepressants have only modest efficacy and require long-term treatment, and are only weakly effective in blocking or reversing these structural changes caused by stress. Recent findings demonstrate that ketamine, an NMDA receptor antagonist, produces rapid antidepressant actions in difficult to treat depressed patients. In addition, preclinical studies demonstrate that ketamine rapidly increases synaptic connections in the prefrontal cortex by increasing glutamate signaling and activation of pathways that control the synthesis of synaptic proteins. Moreover, ketamine rapidly reverses the synaptic deficits caused by exposure to chronic stress in rodent models. Studies of the signaling mechanisms underlying the actions of ketamine have provided novel approaches and targets for new rapid acting antidepressants with decreased side effects, as well as a better understanding of the neurobiology of stress, depression, and treatment response. © 2014 Wiley Periodicals, Inc.

  3. Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder.

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    Peterson, Kimberly; Dieperink, Eric; Anderson, Johanna; Boundy, Erin; Ferguson, Lauren; Helfand, Mark

    2017-06-01

    This study aims to conduct an evidence review of the effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment for major depressive disorder. We searched MEDLINE®, the Cochrane Central Registry of Controlled Trials, and PsycINFO through February 2017. We used prespecified criteria to select studies, abstract data, and rate internal validity and strength of the evidence (PROSPERO number CRD42016036358). We included two randomized trials (RCT), five controlled cohort studies, and six modeling studies of mostly women in their mid-40s with few comorbidities. CNSDose (ABCB1, ABCC1, CYP2C19, CYP2D6, UGT1A1) is the only pharmacogenomics test that significantly improved remission (one additional remitting patient in 12 weeks per three genotyped, 95% CI 1.7 to 3.5) and reduced intolerability in an RCT. ABCB1 genotyping leads to one additional remitting patient in 5 weeks per three genotyped (95% CI 3 to 20), but tolerability was not reported. In an RCT, GeneSight (CYP2D6, CYPC19, CYP1A2, SLC6A4, HTR2A) did not statistically significantly improve remission, and evidence is inconclusive about its tolerability. Evidence is generally low strength because RCTs were few and underpowered. Cost-effectiveness is unclear due to lack of directly observed cost-effectiveness outcomes. We found no studies that evaluated whether pharmacogenomics shortens time to optimal treatment, whether improvements were due to switches to genetically congruent medication, or whether effectiveness varies based on test and patient characteristics. Certain pharmacogenomics tools show promise of improving short-term remission rates in women in their mid-40s with few comorbidities. But, important evidence limitations preclude recommending their widespread use and indicate a need for further research.

  4. Scopolamine rapidly increases mammalian target of rapamycin complex 1 signaling, synaptogenesis, and antidepressant behavioral responses.

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    Voleti, Bhavya; Navarria, Andrea; Liu, Rong-Jian; Banasr, Mounira; Li, Nanxin; Terwilliger, Rose; Sanacora, Gerard; Eid, Tore; Aghajanian, George; Duman, Ronald S

    2013-11-15

    Clinical studies report that scopolamine, an acetylcholine muscarinic receptor antagonist, produces rapid antidepressant effects in depressed patients, but the mechanisms underlying the therapeutic response have not been determined. The present study examines the role of the mammalian target of rapamycin complex 1 (mTORC1) and synaptogenesis, which have been implicated in the rapid actions of N-methyl-D-aspartate receptor antagonists. The influence of scopolamine on mTORC1 signaling was determined by analysis of the phosphorylated and activated forms of mTORC1 signaling proteins in the prefrontal cortex (PFC). The numbers and function of spine synapses were analyzed by whole cell patch clamp recording and two-photon image analysis of PFC neurons. The actions of scopolamine were examined in the forced swim test in the absence or presence of selective mTORC1 and glutamate receptor inhibitors. The results demonstrate that a single, low dose of scopolamine rapidly increases mTORC1 signaling and the number and function of spine synapses in layer V pyramidal neurons in the PFC. Scopolamine administration also produces an antidepressant response in the forced swim test that is blocked by pretreatment with the mTORC1 inhibitor or by a glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist. Taken together, the results demonstrate that the antidepressant actions of scopolamine require mTORC1 signaling and are associated with increased glutamate transmission, and synaptogenesis, similar to N-methyl-D-aspartate receptor antagonists. These findings provide novel targets for safer and more efficacious rapid-acting antidepressant agents. © 2013 Society of Biological Psychiatry.

  5. FMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties.

    Science.gov (United States)

    Wolfe, Sarah A; Workman, Emily R; Heaney, Chelcie F; Niere, Farr; Namjoshi, Sanjeev; Cacheaux, Luisa P; Farris, Sean P; Drew, Michael R; Zemelman, Boris V; Harris, R Adron; Raab-Graham, Kimberly F

    2016-09-26

    Alcohol promotes lasting neuroadaptive changes that may provide relief from depressive symptoms, often referred to as the self-medication hypothesis. However, the molecular/synaptic pathways that are shared by alcohol and antidepressants are unknown. In the current study, acute exposure to ethanol produced lasting antidepressant and anxiolytic behaviours. To understand the functional basis of these behaviours, we examined a molecular pathway that is activated by rapid antidepressants. Ethanol, like rapid antidepressants, alters γ-aminobutyric acid type B receptor (GABABR) expression and signalling, to increase dendritic calcium. Furthermore, new GABABRs are synthesized in response to ethanol treatment, requiring fragile-X mental retardation protein (FMRP). Ethanol-dependent changes in GABABR expression, dendritic signalling, and antidepressant efficacy are absent in Fmr1-knockout (KO) mice. These findings indicate that FMRP is an important regulator of protein synthesis following alcohol exposure, providing a molecular basis for the antidepressant efficacy of acute ethanol exposure.

  6. Effects of antidepressant drugs on emotion.

    Science.gov (United States)

    Serra, Montserrat; Salgado-Pineda, Pilar; Delaveau, Pauline; Fakra, Eric; Gasto, Cristobal; Blin, Olivier

    2006-01-01

    Until recently, scant attention has been paid to the effect of antidepressant drugs on emotion, and we have little knowledge about the way antidepressant drugs modulate neural processing of emotional and affective information, or their relationship to mood changes. Numerous behavioral studies have examined the impact of depression on the recognition of facial expressions. Although conflicting results have been obtained, depressive patients seem to attribute a different emotional valence to these stimuli than do control subjects. Recent studies have shown that a single dose of an antidepressant can increase the processing of positively versus negatively valenced material in nondepressed volunteers. Such psychopharmacological effects may ameliorate the negative biases that characterize mood disorders. Antidepressants may therefore work in a manner comparable with that of psychologic treatments that aim to redress negative biases in information processing. Studies with functional neuroimaging also show that emotional processes are dependent upon a variety of structures; most which form part of the limbic system and are altered in depression. Other studies have demonstrated changes in these structures during antidepressant treatment, mainly in the amygdala. Future research should attempt to explain, for example, the implications of changes in early emotional processing on mood and remission of depression, and the differences between acute and chronic treatment.

  7. Cardiovascular Effects of Antidepressants and Mood Stabilizers

    Directory of Open Access Journals (Sweden)

    Shahin Akhondzadeh

    2007-08-01

    Full Text Available Depression is a serious disorder in today’s society, with the estimates of lifetime prevalence being as high as 21% of the general population in some developed countries. As defined by the American Psychiatric Association, depression is a heterogeneous disorder often manifested with symptoms at the psychological, behavioral, and physiological levels. Such patients are often reluctant to take synthetic antidepressants in their appropriate doses due to their anticipated side effects including inability to drive a car, dry mouth, constipation, and sexual dysfunction. As a therapeutic alternative, effective herbal drugs may offer advantages in terms of safety and tolerability, possibly also improving patient compliance. The advent of the first antidepressants, Monoamine Oxidase Inhibitors (MAOIs and Tricyclic Antidepressants (TCAs, in the 1950s and 1960s represented a dramatic leap forward in the clinical management of depression. The subsequent development of the Selective Serotonin Reuptake Inhibitors (SSRIs and the Serotonin Norepinephrine Reuptake Inhibitor (SNRI venlafaxine in the past decade and a half has greatly enhanced the treatment of depression by offering patients medications that are as effective as the older agents but are generally more tolerable and safer in an overdose. The introduction of atypical antidepressants, such as bupropion, nefazadone, and mirtazapine, has added substantially to the available pharmacopoeia for depression. Nonetheless, rates of remission tend to be low and the risk of relapse and recurrence remains high. One of the concerns regarding the safety of antidepressant is its potential risk of cardiotoxicity and cardiovascular side effects. In this review, we will focus on the cardiovascular side effects of different types of antidepressants.

  8. Effects of antidepressant drugs on sexual function.

    Science.gov (United States)

    Baldwin, D S; Thomas, S C; Birtwistle, J

    1997-01-01

    Adequate sexual expression is an essential part of human relationships, enhancing quality of life and providing a sense of physical, psychological and social well-being. Unfortunately, depression is associated with impairments of sexual function and satisfaction. These problems can worsen a quality of life that is already reduced by the effects of depressive illness. The existing antidepressant drugs are far from ideal, most having adverse effects on sexual function. Unfortunately, the exact incidence of sexual dysfunction during treatment with many antidepressants is not known. Disturbances of sexual interest and performance will only be detected in a reliable fashion when systematic enquiries are made during the course of the standard clinical interview. Growing awareness of the adverse effects of many antidepressants on sexual function has led to some re-evaluation of the earlier claims for the good tolerability of many of the newer drugs. There is a clear need for further well-designed controlled studies of the effects of antidepressants on sexual function, so that this aspect of the tolerability of differing drugs can be assessed more reliably. (IntJ Psych Clin Pract 1997; 1: 47-58).

  9. Jieyuanshen decoction exerts antidepressant effects on depressive ...

    African Journals Online (AJOL)

    Conclusion: JYAS-D had a significant antidepressant-like effect on rat model through regulating serum concentration of CORT, ACTH and CRH, increasing the content of hippocampus GR and regulating the equilibrium of amino acids neurotransmitter. Keywords: Hypothalamic-pituitary-adrenal (HPA) axis; Glucocorticoid/ ...

  10. [Antidepressant and tolerance: Determinants and management of major side effects].

    Science.gov (United States)

    David, D J; Gourion, D

    2016-12-01

    need to take into account the key role of the nocebo effect in the occurrence of adverse effects. The next generation of antidepressant would aim to have a rapid efficacy in patients unresponsive or resistant to drugs currently available while improving certain effects of tolerance through an optimization of their psychopharmacological properties leading to a reduction of their side effects. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  11. Antidepressant Prescription and Suicide Rates: Effect of Age and Gender

    Science.gov (United States)

    Kalmar, Sandor; Szanto, Katalin; Rihmer, Zoltan; Mazumdar, Sati; Harrison, Katrin; Mann, J. John

    2008-01-01

    To determine whether the effect of antidepressant exposure on suicide rate is modified by age and gender in Hungary, annual antidepressant prescription rates and suicide rates of about 10 million inhabitants between 1999-2005 were analyzed by age and gender groups. The suicide rate was inversely related to the increased use of antidepressants in…

  12. Antidepressant effects of Mentha pulegium in mice

    Directory of Open Access Journals (Sweden)

    Zahra Rabiei

    2016-09-01

    Full Text Available The aim of this study is to investigate the antidepressant effects of Mentha pulegium essential oil in BALB/c mice. Six experimental groups (7 mice each were used. Forced swim test was performed 30 min after essential oil injection. In the groups receiving M. pulegium essential oil (50, 75 and 100 mg/kg, immobility duration significantly decreased compared to the control group. M. pulegium (50 and 75 mg/kg resulted in significant decrease in nitrate/nitrite content in serum compared to the control group. M. pulegium essential oil antidepressant effect that may be due to the inhibition of oxidative stress. The results showed that decrease in nitrate/nitrite content in serum and high anti-oxidant effects of M. pulegium essential oil.

  13. Neurogenesis and The Effect of Antidepressants

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2006-01-01

    Full Text Available The recent evidence that neurogenesis occurs throughout adulthood and neural stem cells (NSCs reside in the adult central nervous system (CNS suggests that the CNS has the potential for self-repair. Beside this potential, the function of newly generated neuronal cells in the adult brain remains the focus of intense research. The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests that adult neurogenesis may contribute to the biology of depression. The observations that antidepressants, like fluoxetine, increase neurogenesis in the dentate gyrus (DG and neurogenesis is required for the behavioral effect of antidepressants, lead to a new theory for depression and the design of new strategies and drugs for the treatment of depression. However, the role of adult neurogenesis in the etiology of depression remains the source of controversies and debates.

  14. Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action

    DEFF Research Database (Denmark)

    Lucas, Guillaume; Rymar, Vladimir V; Du, Jenny

    2007-01-01

    Current antidepressants are clinically effective only after several weeks of administration. Here, we show that serotonin(4) (5-HT(4)) agonists reduce immobility in the forced swimming test, displaying an antidepressant potential. Moreover, a 3 day regimen with such compounds modifies rat brain p...

  15. Facebook enhances antidepressant pharmacotherapy effects.

    Science.gov (United States)

    Mota Pereira, Jorge

    2014-01-01

    Treatment-resistant major depressive disorder (TR-MDD) is a complex condition, with very low remission rates. In recent years some studies have been conducted on the implementation of cognitive behavioral therapy and psychodynamic psychotherapy interventions via the Internet to MDD patients, and results have been promising. However, there have been no studies in patients with TR-MDD nor with the use of Facebook with the psychiatrist as "friend." 60 TR-MDD patients were randomized to one of three groups: Facebook group with psychiatrist as "friend," Facebook group without psychiatrist as "friend," and control group (no Facebook use). Both Facebook groups spent at least 1 hour/day on Facebook, 7 days/week, during the 3 months. All patients maintained their usual pharmacotherapy. All participants were evaluated at baseline and at 1, 2, and 3 months for depressive symptoms using HAD17 and BDI-II. Results show that both Facebook groups had a decrease on HADM17 and BDI-II scores as well as higher remission and response rates than the control group, with better results if the psychiatrist was a "friend" on Facebook. Therefore, in TR-MDD, Facebook can be used as an effective enhancement therapy, adjuvant to pharmacological therapy with regular consultations, especially if the psychiatrist is the patient's online "friend."

  16. Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan.

    Directory of Open Access Journals (Sweden)

    Linda Nguyen

    Full Text Available Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (σ1 receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of σ1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, σ1 receptor antagonists (BD1063 and BD1047 were evaluated in conjunction with dextromethorphan to determine the involvement of σ receptors in its antidepressant-like effects. Quinidine, a cytochrome P450 (CYP 2D6 inhibitor, was also evaluated in conjunction with dextromethorphan to increase the bioavailability of dextromethorphan and reduce exposure to additional metabolites. Finally, saturation binding assays were performed to assess the manner in which dextromethorphan interacts at the σ1 receptor. Our results revealed dextromethorphan displays antidepressant-like effects in the forced swim test that can be attenuated by pretreatment with σ1 receptor antagonists, with BD1063 causing a shift to the right in the dextromethorphan dose response curve. Concomitant administration of quinidine potentiated the antidepressant-like effects of dextromethorphan. Saturation binding assays revealed that a Ki concentration of dextromethorphan reduces both the Kd and the Bmax of [(3H](+-pentazocine binding to σ1 receptors. Taken together, these data suggest that dextromethorphan exerts some of its antidepressant actions through σ1 receptors.

  17. Is the antidepressive effect of second-generation antidepressants a myth?

    DEFF Research Database (Denmark)

    Bech, P

    2010-01-01

    Two recent meta-analyses on second-generation antidepressants versus placebo in mild to moderate forms of major depression, based on data on all randomized clinical trials using the Hamilton Depression Scale (HAMD) submitted to FDA, have shown an effect size of approximately 0.30 in favour...

  18. Effectiveness of a smartphone app for guiding antidepressant drug selection.

    Science.gov (United States)

    Man, Colin; Nguyen, Cathina; Lin, Steven

    2014-09-01

    Major depression is a prevalent chronic disease in the United States. However, many physicians lack access to decision support tools at point of care to help choose antidepressants in a rational, evidence-based manner. A patient-centered treatment model that uses a symptom-based approach to selecting antidepressants was developed into a smartphone application to provide instant, evidence-based recommendations and drug monographs. The purpose of this study was to assess the impact of this mobile application on the confidence level of family physicians in treating depression. The smartphone application was provided to 14 family medicine residents and attending physicians from the O'Connor Family Medicine Residency Program in San Jose, CA. Participants were asked to use the software as drug reference and clinical decision support during patient care activities. Three surveys were administered over a 12-week period to assess provider characteristics, outcome measures (ie, confidence in managing depression and choosing an initial antidepressant based on patient symptoms, medical comorbidities, potential side effects, and drug interactions), and fund of antidepressant knowledge. The average confidence levels in managing depression, starting an antidepressant on a patient with depression, and choosing an initial antidepressant based on patient symptoms increased significantly within the period of smartphone application usage. The average scores on the antidepressant knowledge tests also improved. The smartphone application was an effective tool for both increasing confidence in depression treatment and educating physicians. Future studies to evaluate the effectiveness and impact of smartphone applications on medical education and postgraduate training are warranted.

  19. Role of NMDA receptor GluN2D subunit in the antidepressant effects of enantiomers of ketamine

    Directory of Open Access Journals (Sweden)

    Soichiro Ide

    2017-11-01

    Full Text Available We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA receptor GluN2D subunit knockout (GluN2D-KO mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The antidepressant effects of (RS-ketamine and (S-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R-ketamine were only observed in wildtype mice. These data suggest that the GluN2D subunit is critical for the sustained antidepressant effects of (R-ketamine.

  20. Isoflurane produces antidepressant effects and induces TrkB signaling in rodents

    DEFF Research Database (Denmark)

    Antila, Hanna; Ryazantseva, Maria; Popova, Dina

    2017-01-01

    A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in ...

  1. Isoflurane produces antidepressant effects and induces TrkB signaling in rodents

    DEFF Research Database (Denmark)

    Antila, Hanna; Ryazantseva, Maria; Popova, Dina

    2017-01-01

    A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects...

  2. Rapid antidepressants stimulate the decoupling of GABAB receptors from GIRK/Kir3 channels through increased protein stability of 14-3-3η

    Science.gov (United States)

    Workman, E R; Haddick, P C G; Bush, K; Dilly, G A; Niere, F; Zemelman, B V; Raab-Graham, K F

    2015-01-01

    A single injection of N-methyl-D-aspartate receptor (NMDAR) antagonists produces a rapid antidepressant response. Lasting changes in the synapse structure and composition underlie the effectiveness of these drugs. We recently discovered that rapid antidepressants cause a shift in the γ-aminobutyric acid receptor (GABABR) signaling pathway, such that GABABR activation shifts from opening inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting dendritic calcium signal and mammalian Target of Rapamycin activity. However, little is known about the molecular and biochemical mechanisms that initiate this shift. Herein, we show that GABABR signaling to Kir3 (GIRK) channels decreases with NMDAR blockade. Blocking NMDAR signaling stabilizes the adaptor protein 14-3-3η, which decouples GABABR signaling from Kir3 and is required for the rapid antidepressant efficacy. Consistent with these results, we find that key proteins involved in GABABR signaling bidirectionally change in a depression model and with rapid antidepressants. In socially defeated rodents, a model for depression, GABABR and 14-3-3η levels decrease in the hippocampus. The NMDAR antagonists AP5 and Ro-25-6981, acting as rapid antidepressants, increase GABABR and 14-3-3η expression and decrease Kir3.2. Taken together, these data suggest that the shift in GABABR function requires a loss of GABABR-Kir3 channel activity mediated by 14-3-3η. Our findings support a central role for 14-3-3η in the efficacy of rapid antidepressants and define a critical molecular mechanism for activity-dependent alterations in GABABR signaling. PMID:25560757

  3. Rapid antidepressants stimulate the decoupling of GABA(B) receptors from GIRK/Kir3 channels through increased protein stability of 14-3-3η.

    Science.gov (United States)

    Workman, E R; Haddick, P C G; Bush, K; Dilly, G A; Niere, F; Zemelman, B V; Raab-Graham, K F

    2015-03-01

    A single injection of N-methyl-D-aspartate receptor (NMDAR) antagonists produces a rapid antidepressant response. Lasting changes in the synapse structure and composition underlie the effectiveness of these drugs. We recently discovered that rapid antidepressants cause a shift in the γ-aminobutyric acid receptor (GABABR) signaling pathway, such that GABABR activation shifts from opening inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting dendritic calcium signal and mammalian Target of Rapamycin activity. However, little is known about the molecular and biochemical mechanisms that initiate this shift. Herein, we show that GABABR signaling to Kir3 (GIRK) channels decreases with NMDAR blockade. Blocking NMDAR signaling stabilizes the adaptor protein 14-3-3η, which decouples GABABR signaling from Kir3 and is required for the rapid antidepressant efficacy. Consistent with these results, we find that key proteins involved in GABABR signaling bidirectionally change in a depression model and with rapid antidepressants. In socially defeated rodents, a model for depression, GABABR and 14-3-3η levels decrease in the hippocampus. The NMDAR antagonists AP5 and Ro-25-6981, acting as rapid antidepressants, increase GABABR and 14-3-3η expression and decrease Kir3.2. Taken together, these data suggest that the shift in GABABR function requires a loss of GABABR-Kir3 channel activity mediated by 14-3-3η. Our findings support a central role for 14-3-3η in the efficacy of rapid antidepressants and define a critical molecular mechanism for activity-dependent alterations in GABABR signaling.

  4. Antidepressant-associated sexual dysfunction: impact, effects, and treatment

    Directory of Open Access Journals (Sweden)

    Agnes Higgins

    2010-09-01

    Full Text Available Agnes Higgins, Michael Nash, Aileen M LynchSchool of Nursing and Midwifery Studies, Trinity College Dublin, Dublin, IrelandAbstract: Sexual dysfunction is a common side effect of antidepressants and can have significant impact on the person’s quality of life, relationships, mental health, and recovery. The reported incidence of sexual dysfunction associated with antidepressant medication varies considerably between studies, making it difficult to estimate the exact incidence or prevalence. The sexual problems reported range from decreased sexual desire, decreased sexual excitement, diminished or delayed orgasm, to erection or delayed ejaculation problems. There are a number of case reports of sexual side effects, such as priapism, painful ejaculation, penile anesthesia, loss of sensation in the vagina and nipples, persistent genital arousal and nonpuerperal lactation in women. The focus of this article is to explore the incidence, pathophysiology, and treatment of antidepressant iatrogenic sexual dysfunction.Keywords: depression, antidepressant, iatrogenic sexual dysfunction, SSRI, SNRI

  5. Rapid improvement of depressive symptoms in suicide attempters following treatment with milnacipran and tricyclic antidepressants – a case series

    Directory of Open Access Journals (Sweden)

    Kirino E

    2011-12-01

    Full Text Available Eiji Kirino, Masao GitohDepartment of Psychiatry, Juntendo University, School of Medicine, Shizuoka, JapanAbstract: Suicide is a serious social problem in many countries, including Japan. The majority of people who commit suicide suffer from depression. Suicide attempt patients suffering from serious physical injuries are initially treated in hospital emergency departments. The present post hoc analysis examined data from patients admitted to an emergency hospital for treatment of physical injuries, resulting from a suicide attempt, and initial psychiatric treatment for depression and prevention of future suicide attempts. The effects on depressive symptoms were studied in two groups of patients using the 17-item Hamilton depression scale (HAMD. One group (n = 6 had received intravenous tricyclic antidepressants (TCA (amitriptyline or clomipramine while the other group (n = 7 had been treated orally with milnacipran, a serotonin and norepinephrine reuptake inhibitor antidepressant. Prior to treatment the four highest scoring items on the HAMD scale were the same in both groups namely, item 1 (depressed mood, item 3 (suicidality, item 7 (interest in work and activities, and item 10 (psychic anxiety. After 1 week of treatment, mean global HAMD scores were significantly reduced in both groups. Treatment resulted in a significant reduction of five HAMD items in the TCA group, whereas in the milnacipran group 12 HAMD items were significantly reduced. Suicidality (item 3 was significantly improved by 1 week treatment with milnacipran, but not by TCAs. Milnacipran rapidly improved a wide range of depressive symptoms, including suicidality within the first week. The improvement with milnacipran would appear to be, at least, equivalent to that achieved with TCAs, possibly affecting a wider range of symptoms. Since milnacipran has been shown in comparative studies to be better tolerated than TCAs, this antidepressant offers an interesting option for the

  6. Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation.

    Science.gov (United States)

    Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

    2014-05-01

    Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory - the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Double-blind, placebo-controlled, randomized, parallel-group study. Sleep laboratory. Twenty-five healthy men (mean age: 26.8 ± 5.6 y). 75 mg amitriptyline versus placebo. To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline.

  7. Evaluation of antidepressant effect of ethanolic extract of Rosa damascena using forced swimming test

    Directory of Open Access Journals (Sweden)

    Karim Dolati

    2011-12-01

    Conclusion: Although ethanolic extract did not have antidepressant effect, we cannot rule out this effect altogether. In our opinion, antidepressant effect is masked by CNS depression effect of ethanolic extract of R. damascena.

  8. Peripheral administration of lactate produces antidepressant-like effects

    KAUST Repository

    Carrard, A

    2016-10-18

    In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.

  9. Toward achieving optimal response: understanding and managing antidepressant side effects

    Science.gov (United States)

    Kelly, Karen; Posternak, Michael; Jonathan, E. Alpert

    2008-01-01

    The safety and tolerability of antidepressants have improved considerably over the past two decades, Nevertheless, antidepressant side effects are still common and problematic. The majority of patients treated with contemporary agents experience one or more bothersome side effects. These side effects often create barriers to achieving depressive remission, as well as to preventing relapse and recurrence. Clinicians tend to underestimate the prevalence of side effects, and as many as one quarter of patients discontinue their antidepressants because of difficult-to-tolerate side effects; others may continue on antidepressant therapy but experience diminished quality of life related to troublesome side effects. This article reviews the prevalence of side effects, the impact of side effects on treatment adherence, and methodological issues including the challenge of distinguishing side effects from residual depressive symptoms, discontinuation effects, and general medical problems. In addition, we address the most common side effects such as sexual dysfunction, gastrointestinal problems, sleep disturbance, apathy, and fatigue, and offer strategies for management that may help patients achieve optimal response to pharmacotherapy. PMID:19170398

  10. The analgesic effect of different antidepressants combined with ...

    African Journals Online (AJOL)

    Background: Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice. Methods: Different groups of six ...

  11. The Effect of Sympathetic Antagonists on the Antidepressant Action ...

    African Journals Online (AJOL)

    Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor ...

  12. Effect of nifedipine, imipramine and sertraline on the antidepressant ...

    African Journals Online (AJOL)

    The objective of the study was to determine the effect of nifedipine, imipramine and sertraline on the acute and long-term antidepressant-like responses of furosemide in the forced swim (FST) and tail suspension (TST) tests in mice. Groups of mice of six in each group were treated for 30 days with Tween 80, furosemide (10 ...

  13. Is off-label repeat prescription of ketamine as a rapid antidepressant safe? Controversies, ethical concerns, and legal implications.

    Science.gov (United States)

    Zhang, Melvyn W; Harris, Keith M; Ho, Roger C

    2016-01-14

    Depressive disorders are a common form of psychiatric illness and cause significant disability. Regulation authorities, the medical profession and the public require high safety standards for antidepressants to protect vulnerable psychiatric patients. Ketamine is a dissociative anaesthetic and a derivative of a hallucinogen (phencyclidine). Its abuse is a major worldwide public health problem. Ketamine is a scheduled drug and its usage is restricted due to its abuse liability. Recent clinical trials have reported that ketamine use led to rapid antidepressant effects in patients suffering from treatment-resistant depression. However, various flaws in study designs, and possible biased reporting of results, may have influenced those findings. Further analyses of ketamine use are needed to ensure patient safety. The use of ketamine in research and treatment of depressive disorders is controversial. Recently, mental health professionals raised ethical concerns about an ongoing ketamine trial in the UK. Also, a Canadian agency reviewed the existing evidence and did not recommend prescribing ketamine to treat depressive disorders. Findings obtained from tightly controlled research settings cannot be easily translated to clinical practice as substance abuse is commonly comorbid with depressive disorders. An effective antidepressant should reduce severity of depressive symptoms without liability problems. Although the US FDA has not approved the use of ketamine to treat depressive disorders, some psychiatrists offer off-label repeat prescription of ketamine. Prescribing ketamine for treating depressive disorders requires substantial empirical evidence. Clinicians should also consider research findings on ketamine abuse. Depressive disorders can be chronic conditions and the current evidence does not rule out the risk of substance abuse after repeat prescription of ketamine. Off-label ketamine use in treating depressive disorders may breach ethical and moral standards

  14. Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling.

    Science.gov (United States)

    Hines, D J; Schmitt, L I; Hines, R M; Moss, S J; Haydon, P G

    2013-01-15

    Major depressive disorder is a debilitating condition with a lifetime risk of ten percent. Most treatments take several weeks to achieve clinical efficacy, limiting the ability to bring instant relief needed in psychiatric emergencies. One intervention that rapidly alleviates depressive symptoms is sleep deprivation; however, its mechanism of action is unknown. Astrocytes regulate responses to sleep deprivation, raising the possibility that glial signaling mediates antidepressive-like actions of sleep deprivation. Here, we found that astrocytic signaling to adenosine (A1) receptors was required for the robust reduction of depressive-like behaviors following 12 hours of sleep deprivation. As sleep deprivation activates synaptic A1 receptors, we mimicked the effect of sleep deprivation on depression phenotypes by administration of the A1 agonist CCPA. These results provide the first mechanistic insight into how sleep deprivation impacts mood, and provide a novel pathway for rapid antidepressant development by modulation of glial signaling in the brain.

  15. Patients' attitudes toward side effects of antidepressants: an Internet survey.

    Science.gov (United States)

    Kikuchi, Toshiaki; Uchida, Hiroyuki; Suzuki, Takefumi; Watanabe, Koichiro; Kashima, Haruo

    2011-03-01

    Patients' attitudes toward side effects of antidepressants are likely to differ according to gender, which has not yet been fully addressed in the literature. From the 228,310 registrants, 1,305 participants who had received antidepressant drugs within the past year were identified with the Yahoo Japan research monitor through four-step screening procedures. Participants were asked as to which side effect(s) they had experienced, whether they had reported those side effects to their physicians, and whether they had taken any action to counteract them. The questionnaire was completed by 1,187 participants. Side effects were reported in 73.4% of the participants; the prevalence of self-reported side effects was significantly higher in men than women (80.4% vs. 68.3%, P <0.05). The percentage of participants who reported side effects to their physicians widely differed depending on the nature of their experience, ranging from 45.7% to 89.9%; the lowest was for sexual dysfunction. The percentage of participants who had taken any action to relieve side effects varied among side effects from 26.3% for sexual dysfunction to 89.5% for dry mouth. Moreover, a lower percentage of women had reported sexual dysfunction to physicians (36.6% vs. 60.7%, P <0.05) and had taken any action to counteract the problem (19.8% vs. 36.9%, P <0.05). Given that patients experienced with antidepressants are likely to be reluctant to report sexual side effects, physicians should be cognizant of the potential presence of sexual dysfunction in patients who are taking antidepressants, especially for women.

  16. A review on antidepressant effect of medicinal plants

    Directory of Open Access Journals (Sweden)

    Zahra Rabiei

    2017-03-01

    Full Text Available Depression is a life-threatening, debilitating, and common disease affecting different segments of community. Chemical and synthetic drugs available to treat this disease cause many adverse effects and may lead to complete recovery in only 50% of patients. At the same time, medicinal plants have been reported to exert optimal pharmacological effects in treating depression in different models. In this review, the relevant articles indexed in the reliable databases PubMed, PubMed central, Scopus and Web of Science were review-ed. The review indicated that most medicinal plants exerted antidepressant effects through synaptic regulation of serotonin, noradrenaline, and dopamine, regulating activity of hypothalamic-pituitary-adrenal axis, reinfor-cing anti-oxidant defense system, and decreasing inflammatory mediators. The medicinal plants and their active compounds can relieve depression through different pathways and hence are considered a new source to produce antidepressants.

  17. Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies.

    Science.gov (United States)

    Dos Santos, Rafael G; Osório, Flávia L; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-03-01

    To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

  18. Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

    Directory of Open Access Journals (Sweden)

    Rafael G. dos Santos

    2016-03-01

    Full Text Available Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline. Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Conclusion: Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

  19. Coping strategies for antidepressant side effects: an Internet survey.

    Science.gov (United States)

    Kikuchi, Toshiaki; Suzuki, Takefumi; Uchida, Hiroyuki; Watanabe, Koichiro; Mimura, Masaru

    2012-12-20

    Patients' coping methods to palliate side effects of antidepressants have not been reported in the literature. Through an Internet survey, 856 participants who were diagnosed with depression and receiving antidepressants were recruited to report on the methods of coping with side effects. They were asked which side effect(s) they experienced and to write freely about the way they tried to counteract these effects. We classified active coping methods into the following sub-types: adjustment of prescriptions, additional medication, complementary therapy, consultation with physicians, and daily relief. The prevalence of active coping differed across side effects (from 26.7%, sexual dysfunction, to 89.5%, dry mouth). Events with a lower percentage of active coping were more likely to be managed with "adjustment of prescriptions": (sexual dysfunction, 41.9%; fatigue, 36.8%; sweating, 20.0%; tremor, 42.5%; and somnolence, 31.8%). Further, a strong negative correlation was found between the percentage of participants reporting an adjustment of prescription and that reporting an active coping (r=-0.907, pnegative methods such as vomiting for nausea and weight gain and drinking alcohol for insomnia. Sampling of subjects were biased due to an Internet survey and diagnosis of depression and experience of side effects were self-reported. Patients with depression use various ways in alleviating antidepressants side effects. Some effects such as sexual dysfunction and fatigue may not be amenable to subjective coping efforts and others are sometimes managed inappropriately, which warrants a prudent attention. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Effect of antidepressants on neuroendocrine axis in humans.

    Science.gov (United States)

    Meltzer, H Y; Fang, V S; Tricou, B J; Robertson, A

    1982-01-01

    Unlike neuroleptic drugs, the effect of antidepressant drugs on the neuroendocrine axis in man is highly variable and may or may not be intimately related to their antidepressant action. However, the limited neuroendocrine data available does shed some light on the mechanism of action of these agents and raises some important questions, particularly about the regulation of PRL secretion and the interaction between various neurotransmitter systems. At one end of the spectrum, the ability of nomifensine and buproprion to lower serum PRL levels, presumably due to their ability to block the reuptake of DA by tuberoinfundibular DA neurons, suggests that it may be necessary to reconsider the conclusion that these neurons lack a DA reuptake mechanism or that these two agents are antidepressant by virtue of their ability to block DA uptake. Similarly, the inability of amphetamine or methylphenidate to decrease serum PRL levels in man suggests important differences between the tuberoinfundibular DA neurons in man and the rat. These findings also call into question the ability of these agents to block DA uptake or increase DA release in the tuberoinfundibular DA neurons. The finding that fluoxetine raises serum PRL levels, even in one subject, whereas zimelidine has not yet been shown to do so, and that fluoxetine does not potentiate the ability of 5-HTP to stimulate PRL secretion, has raised important questions about the role of 5-HT in PRL and GH regulation in man and the relationship between 5-HT and DA neurons in man. The occasional increase in serum PRL levels found in patients treated with lithium or the MAO inhibitor phenelzine are suggestive of important interindividual differences which may be revealed by neuroendocrine studies, differences which could be valuable in understanding the mechanism of action of these agents - e.g., does lithium decrease DA receptor sensitivity? - and fundamental aspects of neuroendocrine regulation - e.g., do the MAO inhibitors

  1. Antidepressants have Anti-inflammatory Effects that may be Relevant to Dermatology: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Shirin Eskeland

    2017-07-01

    Full Text Available There is increasing evidence of clinically relevant anti-inflammatory effects of monoaminergic antidepressants. PubMed and Ovid databases were searched systematically for the use and efficacy of antidepressants in association with 5 common inflammatory skin disorders: chronic urticaria, psoriasis, atopic dermatitis, other eczema, and alopecia areata. From January 1984 to June 2016, publications included a total of 1,252 dermatological patients in 28 trials or case reports. These unambiguously reported a reduced burden of dermatological symptoms in relation to treatment with antidepressants. Several randomized controlled trials of first-generation antidepressants have been published, while studies of modern antidepressants are usually open-label, yet more informative, regarding patients’ characteristics and study procedures. These overall positive findings may indicate a rationale, beyond treating comorbid psychiatric disorders, for the use of antidepressants in dermatology. Further research into modern tolerable antidepressants, including selective serotonin re-uptake inhibitors, mirtazapine and bupropion, is required.

  2. Effects of antidepressants on function and viability of human neutrophils

    NARCIS (Netherlands)

    Strümper, Danja; Durieux, Marcel E.; Hollmann, Markus W.; Tröster, Barbara; den Bakker, Christel G.; Marcus, Marco A. E.

    2003-01-01

    BACKGROUND: Antidepressants are frequently used in chronic pain therapy and are under investigation as long-acting local anesthetics. Because of the structural similarities between antidepressants and local anesthetics, the authors hypothesized that these compounds act similarly, and they

  3. How does media coverage effect the consumption of antidepressants? A study of the media coverage of antidepressants in Danish online newspapers 2010-2011.

    Science.gov (United States)

    Green Lauridsen, Michael; Kälvemark Sporrong, Sofia

    2017-08-02

    The news media has become a major source of health information for the public, and hence vital in the individuals' opinions and decisions about health topics. The first decrease in the usage of antidepressants in Denmark in over a decade happened alongside an intensive period of media coverage about antidepressants. The aim of this study was to examine the Danish media's coverage of antidepressants during 2010-2011 in order to explore what influence it could have had on the change in the use of antidepressants. Three media theoretical concepts, agenda-setting, priming and framing, were used to explain the media influence with regard to which subject the public should think about, which criteria the public should judge the subject by, and how the public should think about the subject. All articles about antidepressants in the main Danish Internet newspapers from 2010-2011 were analyzed via quantitative and qualitative content analyses. The quantitative analysis was used to determine agenda-setting (number of articles) and, by coding articles, how priming was used in the descriptions of antidepressants. In the qualitative analysis, all articles were analyzed and condensed to determine which frames were used. Quantitative results: 271 articles were included. Agenda-setting was shown by a marked increase in the number of articles about antidepressants. Eight main codes were identified, with the negatively-associated side effects being the major one, thereby priming the public to use side effects as a criterion when judging antidepressants. Qualitative results: Two main frames were identified: 1) economic profits vs. medicine safety, and 2) the necessity of antidepressants. Both frames presented a critical view on antidepressants. It is believed that the media's agenda-setting, priming and framing of antidepressants led the public to have a more skeptical view on antidepressants, which may have probably contributed to a decrease in the usage of antidepressants

  4. Antidepressant and Anxiolytic Effects of Cod Liver Oil in Rats

    Directory of Open Access Journals (Sweden)

    Tahira Perveen*, Faiza Razi, Saida Haider, Hina Qayyum and Darakhshaan J. Haleem

    2013-01-01

    Full Text Available Cod-liver oil is a rich source of omega 3 fatty acids and has been widely used as omega 3 fatty acids supplementation. Regarding omega-3 fatty acid beneficial effects in humans, this study was designed to investigate the effect of repeated administration of cod-liver oil on the locomotion and behaviors of rats, including depression, anxiety and the 5-Hydroxy tryptamine (5-HT metabolism. After four weeks oral administration of cod-liver oil, open field test was used to measure the locomotor and exploratory activity. Elevated plus maze test was used to measure anxiety. Cod-liver oil significantly increased locomotion and produced anxiolytic effects in rats. Antidepressant effect of cod-liver oil was monitored by forced swim test (FST in which struggling time of test animals was increased significantly. 5-HT turnover also increased significantly following the oral repeated administration of cod liver oil in test animals. The results suggest that cod-liver oil has antidepressant and anti-anxiety effects.

  5. Physicians' beliefs about placebo and nocebo effects in antidepressants - an online survey among German practitioners.

    Science.gov (United States)

    Kampermann, Lea; Nestoriuc, Yvonne; Shedden-Mora, Meike C

    2017-01-01

    While substantial placebo and nocebo effects have been documented in antidepressant clinical trials, physicians' awareness of the nonspecific effects in routine antidepressant treatment remains unclear. The study investigated physicians' beliefs and explanatory models regarding the desired effects and undesired side effects of antidepressants, with specific emphasis on nonspecific effects accounted for by placebo and nocebo mechanisms. An online survey was conducted among 87 physicians (40.2% psychiatrists, 25.3% neurologists, 24.1% general practitioners, 12.6% internists, 21.8% other). The survey assessed the physician's beliefs in antidepressant effectiveness, as well as 6 explanatory models regarding antidepressant effectiveness and 8 explanatory models for the occurrence of side effects. Most physicians (89.7%) believed in the effectiveness of antidepressants while acknowledging a considerable role of the placebo effect by attributing around 40% of the total effects to nonspecific factors. For both antidepressant effectiveness and the occurrence of side effects, pharmacological effects were rated as most important (93.1% and 80.5% agreement), but physicians also attributed a substantial role to the patients' expectations (63.2% and 58.6%) and experiences (60.9% and 56.3%). Concerning the physician's own role in promoting nonspecific effects in antidepressant effectiveness, highest endorsements were found for the quality of the physician-patient-relationship (58.6%) and own expectations (41.4%). When asked about side effects, fewer participants agreed that informing the patient about known side effects (25.2%) or the physicians' expectations themselves (17.2%) could induce side effects. Physicians, when prescribing antidepressants, are generally open towards nonspecific treatment mechanisms. However, they consider their own influence as less important than the patient's side, especially when it comes to the explanation of unwanted side effects. Awareness of the

  6. Effects of Calcium Channel Blockers on Antidepressant Action of Alprazolam and Imipramine

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2007-01-01

    Full Text Available Alprazolam is effective as an anxiolytic and in the adjunct treatment of depression. In this study, the effects of calcium channel antagonists on the antidepressant action of alprazolam and imipramine were investigated. A forced swimming maze was used to study behavioral despair in albino mice. Mice were divided into nine groups (n = 7 per group. One group received a single dose of 1% Tween 80; two groups each received a single dose of the antidepressant alone (alprazolam or imipramine; two groups each received a single dose of the calcium channel blocker (nifedipine or verapamil; four groups each received a single dose of the calcium channel blocker followed by a single dose of the antidepressant (with same doses used for either in the previous four groups. Drug administration was performed concurrently on the nine groups. Our data confirmed the antidepressant action of alprazolam and imipramine. Both nifedipine and verapamil produced a significant antidepressant effect (delay the onset of immobility when administered separately. Verapamil augmented the antidepressant effects of alprazolam and imipramine (additive antidepressant effect. This may be due to the possibility that verapamil might have antidepressant-like effect through different mechanism. Nifedipine and imipramine combined led to a delay in the onset of immobility greater than their single use but less than the sum of their independent administration. This may be due to the fact that nifedipine on its own might act as an antidepressant but blocks one imipramine mechanism that depends on L-type calcium channel activation. Combining nifedipine with alprazolam produced additional antidepressant effects, which indicates that they exert antidepressant effects through different mechanisms.

  7. Are gender differences important for the clinical effects of antidepressants?

    DEFF Research Database (Denmark)

    Hildebrandt, Malene Grubbe; Steyerberg, Ewout Willem; Stage, Kurt Bjerregaard

    2003-01-01

    /day), and moclobemide (400 mg/day). Assessments were performed by using the 17-item Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. In a subgroup of 110 patients, weekly measurements of clomipramine plasma concentrations were obtained. Nonparametric statistical tests....... The plasma concentrations of clomipramine were significantly higher for female than for male patients. No gender differences were found in posttreatment Hamilton depression scale scores, nor did the therapeutic effects of treatment depend on gender. Rates of dropout and side effects were similar for men...... and women. No relationship between plasma concentrations, gender, and therapeutic outcome was found. CONCLUSIONS: In a group of patients with major and predominantly melancholic depression, differentiation according to gender was not important in treatment with common antidepressants. Women appeared to have...

  8. Side effects of antidepressants during long-term use in a naturalistic setting

    NARCIS (Netherlands)

    Bet, P.M.; Hugtenburg, J.G.; Penninx, B.W.J.H.; Hoogendijk, W.J.G.

    2013-01-01

    Side effects of antidepressants are usually underreported in clinical trials and large scale naturalistic studies are restricted to six months of use. We examined the prevalence and nature of patient-perceived side effects and their determinants during long-term antidepressant use in a naturalistic

  9. Side effects of antidepressants during long-term use in a naturalistic setting

    NARCIS (Netherlands)

    P.M. Bet (Pierre); J.G. Hugtenburg (Jacqueline); B.W.J.H. Penninx (Brenda); W.J.G. Hoogendijk (Witte)

    2013-01-01

    textabstractSide effects of antidepressants are usually underreported in clinical trials and large scale naturalistic studies are restricted to six months of use. We examined the prevalence and nature of patient-perceived side effects and their determinants during long-term antidepressant use in a

  10. Atypical Antidepressants

    Science.gov (United States)

    ... which is also used to treat insomnia Vortioxetine (Trintellix) Side effects may occur with antidepressants, including atypical ... traz_imtb_ins.pdf. Accessed May 23, 2016. Trintellix (prescribing information). Deerfield, Ill.: Takeda Pharmaceuticals; 2016. http:// ...

  11. Antidepressant Effect of Thymoquinone in Animal Models of Depression.

    Science.gov (United States)

    Aquib, M; Najmi, A K; Akhtar, M

    2015-09-01

    The present study was carried out to determine the role of thymoquinone (TQ) in modulating the levels of neurotransmitter and reducing the oxidative stress in animal models of depression. Mice were divided into 5 groups, each group had 6 animals. TQ (20 mg/kg) in corn oil and fluoxetine (10 mg/kg) in normal saline were administered intraperitoneally (i.p.) half an hour before performing behavioural tests. Modified forced swim test (MFST) and tail suspension test (TST) were used to assess the antidepressant effect in mice. Animals were sacrificed and their brains were removed for biochemical estimation after performing behavioural tests. TQ treatment showed increased swimming, climbing and decreased immobility times in MFST and TST. Combination of TQ with fluoxetine in MFST and TST showed potentiating effect in the present study. A significant elevation of 5-hydroxytryptamine (5-HT) levels was observed following TQ administration in the behavioural models studied. MFST and TST reduced glutathione and elevated TBARS levels in mice. Pre-treatment of TQ restored glutathione and decreased TBARS levels. TQ combination with fluoxetine also showed reduction of TBARS and increased glutathione levels. TQ demonstrated antidepressant effects in MFST and TST respectively in the present study. It further demonstrated antioxidant effects by reducing thiobarbituric acid reactive substance (TBARS) and increasing reduced glutathione (GSH) levels. Although our results are preliminary, further investigations may be required however, based on afore mentioned results, it may be suggested that TQ could be a potential candidate for the management of depression. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Effective Vortioxetine Dose Varies with Extent of Antidepressant Use Across Countries.

    Science.gov (United States)

    Tegin, Cuneyt; Tegin, Gulay; El-Mallakh, Rif S

    2018-01-15

    One of the possible explanations for the antidepressant resistance is tolerance to the effect of increasing synaptic serotonin. Vortioxetine is thought to work through a combination of two pharmacological modes of action: serotonin reuptake inhibition and modification of serotonin receptor activity, in a dose-dependent manner. This mechanism of action allows for examination of the hypothesis that antidepressant non-response may be due to exposure to persistently elevated synaptic amine levels. We hypothesized that lower doses of vortioxetine, which exclusively inhibit serotonin reuptake, would not be effective in the setting of prolonged exposure to antidepressants, but higher doses, which interact in various ways to multiple post-synaptic serotonin receptors, would be relatively more effective in the setting of prolonged, prestudy antidepressant exposure. We examined the relationship between Defined Daily Dose (DDD), which is a measure of the extent of antidepressant use in each country, and the minimal effective dose of vortioxetine. There is a significant relationship between the DDD and effective vortioxetine dose (P = 0.035). In countries with high antidepressant utilization, higher doses of vortioxetine were required, and obverse was true in countries with lower antidepressant utilization. These data support the hypothesis that tolerance to serotonin reuptake inhibition drives poor antidepressant response.

  13. nfluence of antidepressants on glucose homeostasis : effects and mechanisms

    NARCIS (Netherlands)

    Derijks, H.J.|info:eu-repo/dai/nl/304840505

    2009-01-01

    Depression has shown to be a common morbidity in patients with diabetes mellitus and comorbid depression in diabetes mellitus patients is frequently treated with antidepressants. It has been postulated that antidepressants may interfere with glucose homeostasis and that the interference of

  14. Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L.

    Science.gov (United States)

    El-Alfy, Abir T; Ivey, Kelly; Robinson, Keisha; Ahmed, Safwat; Radwan, Mohamed; Slade, Desmond; Khan, Ikhlas; ElSohly, Mahmoud; Ross, Samir

    2010-06-01

    The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Delta(9)-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lacking hypothermic and cataleptic effects (1.25, 2.5, and 5 mg/kg, i.p.), both Delta(9)-THC and Delta(8)-THC showed a U-shaped dose response with only Delta(9)-THC showing significant antidepressant-like effects at 2.5 mg/kg (pcannabidiol (CBD) exhibited significant effect at 20 and 200mg/kg, respectively (p<0.01). The antidepressant-like action of Delta(9)-THC and CBC was further confirmed in the TST. Delta(9)-THC exhibited the same U-shaped dose response with significant antidepressant-like action at 2.5 mg/kg (p<0.05) while CBC resulted in a significant dose-dependent decrease in immobility at 40 and 80 mg/kg doses (p<0.01). Results of this study show that Delta(9)-THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis. Published by Elsevier Inc.

  15. Antidepressant effects on emotional temperament: toward a biobehavioral research paradigm for major depressive disorder.

    Science.gov (United States)

    Soskin, David P; Carl, Jenna R; Alpert, Jonathan; Fava, Maurizio

    2012-06-01

    Given the limited efficacy of current pharmacotherapy for major depressive disorder (MDD) and the historical decline in antidepressant development, there is increasing clinical urgency to develop more effective treatments. To synthesize findings from clinical psychology and affective neuroscience related to the construct of emotional temperament; to examine the effects of antidepressants on the temperament dimensions of positive (PA) and negative affectivity (NA); and to propose a biobehavioral research paradigm for the treatment of MDD. We begin with an introduction to PA and NA, which emphasizes their construct development, historical context, and relevance to psychopathology. We then review studies of antidepressant effects on PA and NA, and explore two related hypotheses: (1) Cause-correction: The antidepressant response may fundamentally occur through changes in emotional temperament, with subsequent spread to syndrome or symptom changes; (2) preferential effects: Antidepressants with different mechanisms of action may have preferential effects on PA or NA. Preliminary findings appear to support the cause-correction hypothesis; there is insufficient clinical evidence to support the preferential effects hypothesis. PA and NA are biologically based temperament dimensions, which modulate emotional, motivational, and behavioral responses to positive and negative incentives. They can be altered by antidepressants, and may independently contribute to depression improvement. In addition, the distinct biobehavioral features of PA and NA suggest that combined pharmacological and cognitive-behavioral treatments targeting these dimensions may have specific, and perhaps, synergistic antidepressant effects. © 2012 Blackwell Publishing Ltd.

  16. Antidepressants: Which Cause the Fewest Sexual Side Effects?

    Science.gov (United States)

    ... a medication to improve sexual function, such as sildenafil (Viagra), tadalafil (Cialis) or vardenafil (Levitra, Staxyn). These medications ... treat sexual problems in men. Limited research suggests sildenafil may improve sexual problems caused by antidepressants in ...

  17. Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine.

    Science.gov (United States)

    Shirayama, Yukihiko; Hashimoto, Kenji

    2018-01-01

    (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine and subsequently to (2R,6R)-hydroxynorketamine in the liver. The metabolism of ketamine to hydroxynorketamine was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the antidepressant effects of these 3 compounds in animal models of depression. The effects of a single i.p. injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-hydroxynorketamine in a rat learned helplessness model were examined. A single dose of (R)-ketamine (20 mg/kg) showed an antidepressant effect in the rat learned helplessness model. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) did so. Unlike (R)-ketamine, its metabolite (2R,6R)-hydroxynorketamine did not show antidepressant actions in the rat learned helplessness model. Therefore, it is unlikely that the metabolism of ketamine to hydroxynorketamine is essential for ketamine's antidepressant actions.

  18. Antidepressant-like effect of modafinil in mice: Evidence for the involvement of the dopaminergic neurotransmission.

    Science.gov (United States)

    Mahmoudi, Javad; Farhoudi, Mehdi; Talebi, Mahnaz; Sabermarouf, Babak; Sadigh-Eteghad, Saeed

    2015-06-01

    Modafinil is a wake-promoting agent that provides wide ranges of neurological effects. There is evidence that it can produce antidepressant effects. This study investigated the antidepressant effect of modafinil in the tail suspension (TST) in mice. Different doses of modafinil was intraperitoneally (ip) administrated and then animals were subjected to TST and/or open field test (OFT). Moreover, the implication of the dopaminergic neurotransmission in modafinil's antidepressant effect was studied. For this purpose, animals were pretreated with haloperidol (non-selective dopamine receptor antagonist), or SCH23390 and sulpiride (the dopamine D1 and D2 receptor antagonist, respectively), then were assessed by TST. The possible effect of sub-effective dose of modafinil in combination with sub-therapeutic doses of standard antidepressants was also evaluated in separate groups. Modafinil (75 mg/kg, ip) produced antidepressant effect in TST, as compared to a control group, without any alterations in ambulation in OFT. Pretreatment of mice with haloperidol (0.2mg/kg, ip) and sulpride (50mg/kg, ip) blocked the anti-immobility effect of modafinil (75 mg/kg, ip). We also found that the administration of SCH23390 (0.05 mg/kg, sc) couldn't antagonize the antidepressant effects of modafinil. In addition, a sub-effective dose of modafinil (50mg/kg, ip) potentiated the sub-effective doses of standard antidepressants including of bupropion (1mg/kg, ip), fluoxetine (1mg/kg, ip) and imipramine (0.1mg/kg, ip) and reduced immobility time in TST. Results show that modafinil induced an antidepressant property in TST and this effect apparently was mediated through interaction with the dopaminergic (D2 receptors) system. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  19. Effect of the multimodal acting antidepressant vortioxetine on rat hippocampal plasticity and recognition memory.

    Science.gov (United States)

    Bétry, Cécile; Etiévant, Adeline; Pehrson, Alan; Sánchez, Connie; Haddjeri, Nasser

    2015-04-03

    Depression is frequently associated with cognitive disturbances. Vortioxetine is a multimodal acting antidepressant that functions as a 5-HT3 and 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter. Given its pharmacological profile, the present study was undertaken to determine whether vortioxetine could modulate several preclinical parameters known to be involved in cognitive processing. In the dorsal hippocampus of anaesthetized rats, the high-frequency stimulation of the Schaffer collaterals provoked a stable long-term potentiation (LTP) of ~25%. Interestingly, vortioxetine (10mg/kg, i.p.) counteracted the suppressant effect of elevated platform stress on hippocampal LTP induction. In the novel object recognition test, vortioxetine (10mg/kg, i.p.) increased the time spent exploring the novel object during the retention test and this pro-cognitive effect was prevented by the partial 5-HT3 receptor agonist SR57227 (1mg/kg, i.p.). Finally, compared to fluoxetine, sustained administration of vortioxetine (5mg/kg/day, s.c.) induced a rapid increase of cell proliferation in the hippocampal dentate gyrus. In summary, vortioxetine prevented the effect of stress on hippocampal LTP, increased rapidly hippocampal cell proliferation and enhanced short-term episodic memory, via, at least in part, its 5-HT3 receptor antagonism. Taken together, these preclinical data suggest that the antidepressant vortioxetine may have a beneficial effect on human cognitive processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Investigation of the antidepressant effects of exopolysaccharides obtained from Marasmius androsaceus fermentation in a mouse model

    National Research Council Canada - National Science Library

    SONG, JIA; XING, GAOYANG; CAO, JIAMING; TENG, LIRONG; LI, CHENLIANG; MENG, QINGFAN; LU, JIAHUI; ZHOU, YULIN; LIU, YANG; WANG, DI; TENG, LESHENG

    2016-01-01

    ...), produced by microorganism secretion, exerts various types of biological activities. The present study aimed to investigate the antidepressant-like effect of the EPS produced during Marasmius androsaceus submerge fermentation (MEPS...

  1. Antidepressant-like Effects of Medial Forebrain Bundle Deep Brain Stimulation in Rats are not Associated With Accumbens Dopamine Release.

    Science.gov (United States)

    Bregman, Tatiana; Reznikov, Roman; Diwan, Mustansir; Raymond, Roger; Butson, Christopher R; Nobrega, José N; Hamani, Clement

    2015-01-01

    Medial forebrain bundle (MFB) deep brain stimulation (DBS) is currently being investigated in patients with treatment-resistant depression. Striking features of this therapy are the large number of patients who respond to treatment and the rapid nature of the antidepressant response. To study antidepressant-like behavioral responses, changes in regional brain activity, and monoamine release in rats receiving MFB DBS. Antidepressant-like effects of MFB stimulation at 100 μA, 90 μs and either 130 Hz or 20 Hz were characterized in the forced swim test (FST). Changes in the expression of the immediate early gene (IEG) zif268 were measured with in situ hybridization and used as an index of regional brain activity. Microdialysis was used to measure DBS-induced dopamine and serotonin release in the nucleus accumbens. Stimulation at parameters that approximated those used in clinical practice, but not at lower frequencies, induced a significant antidepressant-like response in the FST. In animals receiving MFB DBS at high frequency, increases in zif268 expression were observed in the piriform cortex, prelimbic cortex, nucleus accumbens shell, anterior regions of the caudate/putamen and the ventral tegmental area. These structures are involved in the neurocircuitry of reward and are also connected to other brain areas via the MFB. At settings used during behavioral tests, stimulation did not induce either dopamine or serotonin release in the nucleus accumbens. These results suggest that MFB DBS induces an antidepressant-like effect in rats and recruits structures involved in the neurocircuitry of reward without affecting dopamine release in the nucleus accumbens. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The effects of antenatal depression and antidepressant treatment on placental gene expression

    Directory of Open Access Journals (Sweden)

    Jocelien DA Olivier

    2015-01-01

    Full Text Available The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy.Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample.In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

  3. Pregnancy and postpartum antidepressant use moderates the effects of sleep on depression.

    Science.gov (United States)

    Stone, Kristen C; Salisbury, Amy L; Miller-Loncar, Cynthia L; Mattera, Jennifer A; Battle, Cynthia L; Johnsen, Dawn M; O'Grady, Kevin E

    2017-10-01

    This study examined the course of antidepressant use, sleep quality, and depression severity from pregnancy through 6-month postpartum in women with and without a depressive disorder during pregnancy. Women (N = 215) were interviewed during pregnancy, 1- and 6-month postpartum. Mixed linear models were used to examine the longitudinal course and inter-relationships for the time-varying variables of antidepressant use, subjective sleep quality, and depression severity. Pregnant women with a depressive disorder who did not use antidepressants had more variable depression severity over time with improvements in depression severity by 6-month postpartum. In contrast, the depression severity of their medicated counterparts remained stable and high throughout. Pregnant women without a depressive disorder had worse sleep quality when using antidepressants compared with when they were not. Antidepressant use significantly strengthened the magnitude of the effect of sleep quality on depression severity in women with a depressive disorder during pregnancy. When prenatally depressed women use antidepressants, their sleep disturbance is more highly linked to depression severity than when they do not. Furthermore, antidepressants are not adequately treating the sleep disturbance of these women or their remitted counterparts, leaving both groups vulnerable to significant negative mental and physical health outcomes.

  4. Effects of information on college students' perceptions of antidepressant medication.

    Science.gov (United States)

    Frankenberger, Kristi A; Frankenberger, William R; Peden, Blaine F; Hunt, Heather L; Raschick, Christopher M; Steller, Emily G; Peterson, Jaclyn A

    2004-01-01

    The authors examined the impact of pharmaceutical companies' advertisements on college students' perceptions of depression and concomitant treatment with antidepressants among 13 male and 31 female undergraduates from a midwestern university. The students were randomly assigned to groups that read either pharmaceutical company advertisements or scientific information about depression and its treatment. The analysis revealed that 40% of the women in the advertisement condition as opposed to 1 woman (6%) in the scientific condition rated themselves as having mild, moderate, or severe depression on the Beck Depression Inventory, second edition. Women in the advertisement condition were significantly more likely to believe that depression required treatment with antidepressant medication and were more willing than women in the scientific condition to suggest antidepressant treatment to others.

  5. S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Indira Mendez-David

    2017-07-01

    rat model, S 47445 (from 1 mg/kg demonstrated a rapid onset of effect on anhedonia compared to venlafaxine and imipramine. In the CORT model, S 47445 demonstrated significant neurogenic effects on proliferation, survival and maturation of hippocampal newborn neurons at doses inducing an antidepressant-like effect. It also corrected CORT-induced deficits of growth and arborization of dendrites. Finally, the antidepressant/anxiolytic-like activities of S 47445 required adult hippocampal neurogenesis in the novelty suppressed feeding test contrary to OF, EPM and ST. The observed increase in hippocampal BDNF levels could be one of the mechanisms of S 47445 responsible for the adult hippocampal neurogenesis increase. Altogether, S 47445 displays robust antidepressant-anxiolytic-like properties after chronic administration through neurogenesis dependent/independent mechanisms and neuroplastic activities. The AMPA-PAM S 47445 could have promising therapeutic potential for the treatment of major depressive disorders or generalized anxiety disorders.

  6. Antidepressants: Get Tips to Cope with Side Effects

    Science.gov (United States)

    ... best antidepressant choice based on genetic makeup. However, genetic testing is a part of — not a replacement for — a thorough psychiatric exam and clinical decisions. Simon G, et al. Unipolar major depression in adults: Choosing initial treatment. http://www.uptodate. ...

  7. Effects of Information on College Students' Perceptions of Antidepressant Medication

    Science.gov (United States)

    Frankenberger, Kristi A.; Frankenberger, William R.; Peden, Blaine F.; Hunt, Heather L.; Raschick, Christopher M.; Steller, Emily G.; Peterson, Jaclyn A.

    2004-01-01

    The authors examined the impact of pharmaceutical companies' advertisements on college students' perceptions of depression and concomitant treatment with antidepressants among 13 male and 31 female undergraduates from a midwestern university. The students were randomly assigned to groups that read either pharmaceutical company advertisements or…

  8. Metabotropic glutamate 5 receptor antagonism is associated with antidepressant-like effects in mice.

    Science.gov (United States)

    Li, Xia; Need, Anne B; Baez, Melvyn; Witkin, Jeffrey M

    2006-10-01

    Antidepressant-like effects of metabotropic glutamate (mGlu)5 receptor antagonists have been reported previously. We now provide definitive identification of mGlu5 receptors as a target for these effects through the combined use of selective antagonists and mice with targeted deletion of the mGlu5 protein. In these experiments, the mGlu5 receptor antagonists 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and the more selective and metabolically stable analog 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) decreased immobility in the mouse forced swim test, a test predictive of antidepressant efficacy in humans. mGlu5 receptor knockout mice had a phenotype in the forced swim test that was congruent with the effects of receptor blockade; mGlu5 receptor knockout mice were significantly less immobile than their wild-type counterparts. Consistent with mGlu5 receptor mediation of the antidepressant-like effects of MPEP, the effects of MPEP were not observed in mGlu5 receptor knockout mice, whereas comparable effects of the tricyclic antidepressant imiprimine remained active in the mutant mice. MPEP and imiprimine resulted in a synergistic antidepressant-like effect in the forced swim test. The drug interaction was not likely because of increased levels of drugs in the brain, suggesting a pharmacodynamic interaction of mGlu5 and monoaminergic systems in this effect. Thus, the present findings substantiate the hypothesis that mGlu5 receptor antagonism is associated with antidepressant-like effects. This mechanism may not only provide a novel approach to the therapeutic management of depressive disorders but also may be useful in the augmentation of effects of traditional antidepressant agents.

  9. Increased use of antidepressants at the end of life

    DEFF Research Database (Denmark)

    Hansen, Dorte Gilså; Rosholm, Jens-Ulrik; Gichangi, Anthony

    2007-01-01

    BACKGROUND: The new antidepressants are generally effective and safe for older people, but may have serious side-effects. The use has been rapidly increasing, but focus on upper age groups has been limited. The pattern of antidepressant use as death approaches has never been analysed. OBJECTIVE: ...

  10. The effect of a three-tier formulary on antidepressant utilization and expenditures.

    Science.gov (United States)

    Hodgkin, Dominic; Parks Thomas, Cindy; Simoni-Wastila, Linda; Ritter, Grant A; Lee, Sue

    2008-06-01

    Health plans in the United States are struggling to contain rapid growth in their spending on medications. They have responded by implementing multi-tiered formularies, which label certain brand medications 'non-preferred' and require higher patient copayments for those medications. This multi-tier policy relies on patients' willingness to switch medications in response to copayment differentials. The antidepressant class has certain characteristics that may pose problems for implementation of three-tier formularies, such as differences in which medication works for which patient, and high rates of medication discontinuation. To measure the effect of a three-tier formulary on antidepressant utilization and spending, including decomposing spending allocations between patient and plan. We use claims and eligibility files for a large, mature nonprofit managed care organization that started introducing its three-tier formulary on January 1, 2000, with a staggered implementation across employer groups. The sample includes 109,686 individuals who were continuously enrolled members during the study period. We use a pretest-posttest quasi-experimental design that includes a comparison group, comprising members whose employer had not adopted three-tier as of March 1, 2000. This permits some control for potentially confounding changes that could have coincided with three-tier implementation. For the antidepressants that became nonpreferred, prescriptions per enrollee decreased 11% in the three-tier group and increased 5% in the comparison group. The own-copay elasticity of demand for nonpreferred drugs can be approximated as -0.11. Difference-in-differences regression finds that the three-tier formulary slowed the growth in the probability of using antidepressants in the post-period, which was 0.3 percentage points lower than it would have been without three-tier. The three-tier formulary also increased out-of-pocket payments while reducing plan payments and total spending

  11. Effects of DNA methylation inhibitors and conventional antidepressants on mice behaviour and brain DNA methylation levels.

    Science.gov (United States)

    Sales, Amanda Juliana; Joca, Sâmia Regiane Lourenço

    2016-02-01

    Stress increases DNA methylation and decreases the expression of genes involved in neural plasticity, while treatment with DNA methyltransferase inhibitors (DNMTi) increases gene expression and induces antidepressant-like effects in preclinical models. Therefore, the aim of the present work was to further investigate the potential antidepressant-like effect induced by DNMTi by evaluating the behavioural effects induced by associating DNMTi treatment with conventional antidepressant drugs in mice submitted to the forced swimming test (FST). In addition, brain levels of DNA methylation were also investigated. Mice received systemic injections of 5-aza-2'-deoxycytidine (5-AzaD, 0.1, 0.2 mg/kg), RG108 (0.1, 0.2, 0.4 mg/kg), desipramine (DES, 2.5, 5, 10 mg/kg) or fluoxetine (FLX, 5, 10, 20, 30 mg/kg) and were submitted to the FST or to the open field test (OFT). Additional groups received a combination of subeffective doses of 5-AzaD or RG108 (DNMTi) with subeffective doses of DES or FLX (antidepressants). Subeffective doses of RG108 (0.1 mg/kg) or 5-AzaD (0.1 mg/kg) in association with subeffective doses of DES (2.5 mg/kg) or FLX (10 mg/kg) induced significant antidepressant-like effects. Effective doses of RG108 (0.2 mg/kg), 5-AzaD (0.2 mg/kg), DES (10 mg/kg) and FLX (20 mg/kg) atenuated stress-induced changes in DNA methylation levels in the hippocampus and prefrontal cortex. None of the treatments induced locomotor effects in the OFT. These results suggest that DNMTi potentiate the behavioural effects of antidepressant drugs in the FST and that antidepressants, as well as DNMTi, are able to modulate stress-induced changes in DNA methylation in brain regions closely associated with the neurobiology of depression.

  12. Adverse Effects of Antidepressants for Chronic Pain: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Carina Riediger

    2017-07-01

    Full Text Available BackgroundAntidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT, there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain.MethodsSystematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis.ResultsOut of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82] followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects.ConclusionOur synthesized data analysis confirmed overall

  13. The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

    Directory of Open Access Journals (Sweden)

    Gorash ZM

    2008-01-01

    Full Text Available Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist. Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments. In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors.

  14. The hippocampus and dorsal raphe nucleus are key brain areas associated with the antidepressant effects of lithium augmentation of desipramine.

    Science.gov (United States)

    Cussotto, Sofia; Cryan, John F; O'Leary, Olivia F

    2017-05-01

    Approximately 50% of depressed individuals fail to achieve remission with first-line antidepressant drugs and a third remain treatment-resistant. When first-line antidepressant treatment is unsuccessful, second-line strategies include dose optimisation, switching to another antidepressant, combination with another antidepressant, or augmentation with a non-antidepressant medication. Much of the evidence for the efficacy of augmentation strategies comes from studies using lithium to augment the effects of tricyclic antidepressants. The neural circuitry underlying the therapeutic effects of lithium augmentation is not yet fully understood. Recently, we reported that chronic treatment with a combination of lithium and the antidepressant desipramine, exerted antidepressant-like behavioural effects in a mouse strain (BALB/cOLaHsd) that did not exhibit an antidepressant-like behavioural response to either drug alone. In the present study, we used this model in combination with ΔFosB/FosB immunohistochemistry to identify brain regions chronically affected by lithium augmentation of desipramine when compared to either treatment alone. The data suggest that the dorsal raphe nucleus and the CA3 regions of the dorsal hippocampus are key nodes in the neural circuitry underlying antidepressant action of lithium augmentation of desipramine. These data give new insight into the neurobiology underlying the mechanism of lithium augmentation in the context of treatment-resistant depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. [The effectiveness of antidepressants in the treatment of chronic non-cancer pain--a review].

    Science.gov (United States)

    Miller, Adam; Rabe-Jabłońska, Jolanta

    2005-01-01

    Antidepressants are often applied in the treatment of chronic pain. Analgesic action of tricyclic antidepressants (TCAs) has been extensively studied and proven. TCAs are associated with a number of adverse effects which are inconvenient for patients. The newer antidepressants have fewer side effects and equivalent efficacy on mood disorders. This article reviews the available publications (mainly placebo-controlled trials) concerning the efficacy of these medications in the treatment of chronic pain. The data regarding selective serotonin reuptake inhibitors (SSRI) are conflicting. Trazodone (a serotonin-reuptake inhibitor as well as a postsynaptic serotonin receptor antagonist) does not appear to be effective for the treatment of chronic pain. No placebo-controlled studies are available for noradrenergic and specific serotoninergic antidepressant (NaSSA)--mirtazapine and noradrenaline reuptake inhibitor (NaRI)--reboxetine. Bupropion, a noradrenaline and dopamine-reuptake inhibitor appears to be effective in the treatment of neuropathic pain. Venlafaxine--selective serotonin and noradrenergic reuptake inhibitors (SNRI) was shown to be effective in the treatment of different kinds of pain. Duloxetine (SNRI) is effective in relieving both the emotional and painful physical symptoms of depression. Additional randomized, controlled trials are necessary to fully evaluate the role of new antidepressants in the treatment of chronic pain.

  16. The effects of tricyclic and 'atypical' antidepressants on spontaneous locomotor activity in rodents.

    Science.gov (United States)

    Tucker, J C; File, S E

    1986-01-01

    With the exception of amineptin, buproprion and nomifensine all tricyclic and 'atypical' antidepressants have been reported to reduce spontaneous motor activity in rodents, after both acute and chronic administration. However, with the diversity of chemical actions of these drugs it is unlikely that a single neurochemical mechanism is underlying this one behavioral effect. These widespread sedative effects have implications for interpreting behavioral changes in other test situations, since sedation generally occurs at doses that fall within the dose-range effective in other tests. We also review the effects on spontaneous motor activity of withdrawal from chronic antidepressant treatment.

  17. Antidepressant-like effect of agmatine is not mediated by serotonin

    DEFF Research Database (Denmark)

    Krass, Maarja; Wegener, Gregers; Vasar, Eero

    2008-01-01

    The aim of this study was to characterize the behavioral effects of systemically administered agmatine in animal models predictive of antidepressant- and anxiolytic-like activity and clarify whether the effects of agmatine depend on the intact serotonergic system. Only the highest dose of agmatine...... tested (50mg/kg) decreased immobility of mice in the forced swimming test. The magnitude of the effect was slightly smaller than that of the tricyclic antidepressant imipramine (15mg/kg). Agmatine did not change the locomotion of mice in the open field. Pretreatment with the tryptophane hydroxylase...... inhibitor PCPA for 3 days resulted in more than 70% drop in the tissue levels of 5-HT and 5-HIIA but did not counteract the antidepressant-like effect of agmatine. The administration of agmatine did not modify behavior of animals in the light-dark compartment test of anxiety. We conclude...

  18. The rapid recovery of 5-HT cell firing induced by the antidepressant vortioxetine involves 5-HT(3) receptor antagonism.

    Science.gov (United States)

    Bétry, Cécile; Pehrson, Alan L; Etiévant, Adeline; Ebert, Bjarke; Sánchez, Connie; Haddjeri, Nasser

    2013-06-01

    The therapeutic effect of current antidepressant drugs appears after several weeks of treatment and a significant number of patients do not respond to treatment. Here, we report the effects of the multi-modal antidepressant vortioxetine (Lu AA21004), a 5-HT(3) and 5-HT(7) receptor antagonist, 5-HT(1B) receptor partial agonist, 5-HT(1A) receptor agonist and 5-HT transporter (SERT) inhibitor, on rat 5-HT neurotransmission. Using in vivo electrophysiological recordings in the dorsal raphe nucleus of anaesthetized rats, we assessed the acute and subchronic effects of vortioxetine and/or the selective 5-HT(3) receptor agonist, SR57227 or the selective 5-HT(1A) receptor agonist flesinoxan, on 5-HT neuronal firing activity. Using ex-vivo autoradiography, we correlated SERT occupancy and presumed 5-HT firing activity. The selective serotonin reuptake inhibitor, fluoxetine, was used as comparator. Importantly, the recovery of 5-HT neuronal firing was achieved after 1 d with vortioxetine and 14 d with fluoxetine. SR57227 delayed this recovery. In contrast, vortioxetine failed to alter the reducing action of 3 d treatment of flesinoxan. Acute dosing of vortioxetine inhibited neuronal firing activity more potently than fluoxetine. SR57227 prevented the suppressant effect of vortioxetine, but not of fluoxetine. In contrast, flesinoxan failed to modify the suppressant effect of vortioxetine acutely administered. Differently to fluoxetine, vortioxetine suppressed neuronal firing without saturating occupancy at the SERT. Vortioxetine produced a markedly faster recovery of 5-HT neuronal firing than fluoxetine. This is at least partly due to 5-HT(3) receptor antagonism of vortioxetine in association with its reduced SERT occupancy.

  19. The effect of anti-depressant Amitriptyline on the immune system

    Directory of Open Access Journals (Sweden)

    Dukan J

    1994-04-01

    Full Text Available We have studied the effect of amitriptyline, a tricyclic anti-depressant drug on several immune parameters of the Balb/c mice in order to evaluate its immunomodulatory effects. Results showed that amitriptyline will potentiates all of the immunocytes functions except for the production of PGE2 by LPS stimulated monocytes. We have also showed that amitriptyline can normalize the immunosuppressive effect of dexamethasone on mice (experimental stress. These results suggest that one of the mechanisms of action of the tricyclic anti-depressant drugs might be through the modulation of the immune system which has been suppressed by stress or distress

  20. Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling

    OpenAIRE

    Hines, D J; Schmitt, L I; Hines, R. M.; Moss, S.J.; Haydon, P.G.

    2013-01-01

    Major depressive disorder is a debilitating condition with a lifetime risk of ten percent. Most treatments take several weeks to achieve clinical efficacy, limiting the ability to bring instant relief needed in psychiatric emergencies. One intervention that rapidly alleviates depressive symptoms is sleep deprivation; however, its mechanism of action is unknown. Astrocytes regulate responses to sleep deprivation, raising the possibility that glial signaling mediates antidepressive-like actions...

  1. [An adult case of cyclic vomiting syndrome in which tricyclic antidepressant was effective].

    Science.gov (United States)

    Hattori, Manabu; Uematsu, Norihiko; Nakazawa, Hideka; Matsukawa, Noriyuki; Yamawaki, Takemori; Ojika, Kosei

    2006-09-01

    A 30-year-old man presented with a 10-year history of recurrent, stereotypic episodes of incapacitating nausea and vomiting. Initially, he had been diagnosed as having superior mesenteric artery syndrome, and had undergone abdominal surgery at age 20. The patient was in good health between episodes. During each episode, oral intake was impossible and total parenteral nutrition and sedation were necessary. Conventional antiemetics such as metoclopramide were not effective, and the 5-HT3 antagonist ondansetron hydrochloride was only partially effective. Investigations into gastrointestinal, hormonal, and metabolic function were unremarkable, as was psychiatric evaluation. Diagnosing this to be an adult case of cyclic vomiting syndrome, we administered amitriptyline hydrochloride; a prophylactic agent for migraine. This resulted in rapid resolution of the episodes, which have not recurred over several years' follow up. Recently, cyclic vomiting syndrome has been considered a subtype of migraine. In the present case, effectiveness of the tricyclic antidepressant amitriptyline hydrochloride indicated that migraine and cyclic vomiting syndrome have a common pathology. Clinicians should be aware that cyclic vomiting syndrome can affect adults as well as children, and that treatment for migraine may be effective.

  2. Brain effects of antidepressants in major depression: a meta-analysis of emotional processing studies.

    Science.gov (United States)

    Delaveau, Pauline; Jabourian, Maritza; Lemogne, Cédric; Guionnet, Sophie; Bergouignan, Loretxu; Fossati, Philippe

    2011-04-01

    A consistent brain activity pattern has been identified in major depression across many resting positron emission tomography (PET) studies. This dysfunctional pattern seems to be normalized by antidepressant treatment. The aim of this meta-analysis was to identify more clearly the pattern associated with clinical improvement of depression following an antidepressant drug treatment, in emotional activation studies using functional magnetic resonance imaging (fMRI). A quantitative Activation Likelihood Estimation (ALE) meta-analysis was performed across 9 emotional activation fMRI and PET studies (126 patients) using the Activation Likelihood Estimation technique. Following the antidepressant drug treatment, the activation of dorsolateral, dorsomedial and ventrolateral prefrontal cortices was increased whereas the activation of the amygdala, hippocampus, parahippocampal region, ventral anterior cingulate cortex, orbitofrontal cortex, and insula was decreased. Additionally, there was a decreased activation in the anterior (BA 32) and posterior cingulate cortices, as well as in the precuneus and inferior parietal lobule, which could reflect a restored deactivation of the default mode network. The small number of emotional activation studies, using heterogeneous tasks, included in the ALE analysis. The activation of several brain regions involved in major depression, in response to emotional stimuli, was normalized after antidepressant treatment. To refine our knowledge of antidepressants' effect on the neural bases of emotional processing in major depression, neuroimaging studies should use consistent emotional tasks related to depressive symptoms and that involve the default mode network, such as self-referential processing tasks. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. The effects of antenatal depression and antidepressant treatment on placental gene expression

    NARCIS (Netherlands)

    Olivier, Jocelien D A; Åkerud, Helena; Skalkidou, Alkistis; Kaihola, Helena; Sundström-Poromaa, Inger

    2015-01-01

    The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene

  4. A study on the antidepressant effect of Danzhi Xiaoyao powder | Lun ...

    African Journals Online (AJOL)

    Mouse models of behavioural despair such as tail suspension test and forced swimming test were used to evaluate the antidepressant effect of Xiaoyao. Results: Danzhi Xiaoyao Powder could shorten the immobility time of mice in the tail suspension and forced swimming despair models, and had a significant effect on them ...

  5. Synthesis of Chlorinated Tetracyclic Compounds and Testing for Their Potential Antidepressant Effect in Mice.

    Science.gov (United States)

    Karama, Usama; Sultan, Mujeeb A; Almansour, Abdulrahman I; El-Taher, Kamal Eldin

    2016-01-05

    The synthesis of the tetracyclic compounds 1-(4,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (5) and 1-(1,8-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl)-N-methylmethanamine (6) as a homologue of the anxiolytic and antidepressant drugs benzoctamine and maprotiline were described. The key intermediate aldehydes (3) and (4) were successfully synthesized via a [4 + 2] cycloaddition between acrolein and 1,8-dichloroanthracene. The synthesized compounds were investigated for antidepressant activity using the forced swimming test. Compounds (5), (6) and (3) showed significant reduction in the mice immobility indicating significant antidepressant effects. These compounds significantly reduced the immobility times at a dose 80 mg/kg by 84.0%, 86.7% and 71.1% respectively.

  6. Synthesis of Chlorinated Tetracyclic Compounds and Testing for Their Potential Antidepressant Effect in Mice

    Directory of Open Access Journals (Sweden)

    Usama Karama

    2016-01-01

    Full Text Available The synthesis of the tetracyclic compounds 1-(4,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl-N-methylmethanamine (5 and 1-(1,8-dichloro-9,10-dihydro-9,10-ethanoanthracen-11-yl-N-methylmethanamine (6 as a homologue of the anxiolytic and antidepressant drugs benzoctamine and maprotiline were described. The key intermediate aldehydes (3 and (4 were successfully synthesized via a [4 + 2] cycloaddition between acrolein and 1,8-dichloroanthracene. The synthesized compounds were investigated for antidepressant activity using the forced swimming test. Compounds (5, (6 and (3 showed significant reduction in the mice immobility indicating significant antidepressant effects. These compounds significantly reduced the immobility times at a dose 80 mg/kg by 84.0%, 86.7% and 71.1% respectively.

  7. Antidepressant-like effects and mechanisms of flavonoids and related analogues.

    Science.gov (United States)

    Guan, Li-Ping; Liu, Bing-Yu

    2016-10-04

    Flavonoids, possessing a basic phenylbenzopyrone core, are important components of the human diet, and are found in many medicinal plants. Flavonoids include chalcones, flavanones and their derivatives. Synthetic and natural isolated flavonoids display an enormous number of biological activities such as antitumor, antiplatelet, anti-malarial, anti-inflammatory, antidepressant and anticonvulsant properties. This review article focuses on the antidepressant-like effect, structure-activity relationship and mechanism of action of total flavonoid extracts isolation from natural sources, flavonoid compounds and their related analogues. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. A review of the effectiveness of antidepressant medications for depressed nursing home residents.

    Science.gov (United States)

    Boyce, Richard D; Hanlon, Joseph T; Karp, Jordan F; Kloke, John; Saleh, Ahlam; Handler, Steven M

    2012-05-01

    Antidepressant medications are the most common psychopharmacologic therapy used to treat depressed nursing home (NH) residents. Despite a significant increase in the rate of antidepressant prescribing over the past several decades, little is known about the effectiveness of these agents in the NH population. To conduct a systematic review of the literature to examine and compare the effectiveness of antidepressant medications for treating major depressive symptoms in elderly NH residents. The following databases were searched with searches completed prior to January 2011 and no language restriction: MEDLINE, Embase, PsycINFO, CINHAL, CENTRAL, LILACS, ClinicalTrials.gov, International Standard Randomized Controlled Trial Number Register, and the WHO International Clinical Trial Registry Platform. Additional studies were identified from citations in evidence-based guidelines and reviews as well as book chapters on geriatric depression and pharmacotherapy from several clinical references. Studies were included if they described a clinical trial that assessed the effectiveness of any currently-marketed antidepressant for adults aged 65 years or older, who resided in the NH, and were diagnosed by DSM criteria and/or standardized validated screening instruments with Major Depressive Disorder, minor depression, dysthymic disorder, or Depression in Alzheimer's disease. A total of eleven studies, including four randomized and seven non-randomized open-label trials, met all inclusion and exclusion criteria. It was not feasible to conduct a meta-analysis because the studies were heterogeneous in terms of study design, operational definitions of depression, participant characteristics, pharmacologic interventions, and outcome measures. Of the four randomized trials, two had a control group and did not demonstrate a statistically-significant benefit for antidepressant pharmacotherapy over placebo. While six of the seven non-randomized studies identified a response to an

  9. Antidepressants and their effect on cognition in major depressive disorder.

    Science.gov (United States)

    Papakostas, George I

    2015-08-01

    Cognitive functioning is a symptom of major depressive disorder (MDD) that deserves particular attention by clinicians and researchers. Despite the fact that cognitive dysfunction represents a symptom of MDD as well as a functional outcome measure, cognition has been insufficiently investigated in antidepressant trials. While, until recently, few placebo-controlled trials have measured cognition in MDD, those examples which did have consisted of older adults. Of agents tested thus far in placebo-controlled trials (citalopram, duloxetine, vortioxetine), only the latter has been studied in patients aged 18-65, and only the latter has been shown to be superior to placebo in improving measures of executive functioning and to do so across adult age groups. Both duloxetine and vortioxetine appear to result in greater improvements than placebo in immediate and delayed memory. Clinicians who wish to improve the psychosocial recovery of patients with MDD should be familiar with studies of new options for treatment. © Copyright 2015 Physicians Postgraduate Press, Inc.

  10. Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats

    Science.gov (United States)

    Choi, Miyeon; Lee, Seung Hoon; Wang, Sung Eun; Ko, Seung Yeon; Song, Mihee; Choi, June-Seek; Duman, Ronald S.; Son, Hyeon

    2015-01-01

    Ketamine produces rapid antidepressant-like effects in animal assays for depression, although the molecular mechanisms underlying these behavioral actions remain incomplete. Here, we demonstrate that ketamine rapidly stimulates histone deacetylase 5 (HDAC5) phosphorylation and nuclear export in rat hippocampal neurons through calcium/calmodulin kinase II- and protein kinase D-dependent pathways. Consequently, ketamine enhanced the transcriptional activity of myocyte enhancer factor 2 (MEF2), which leads to regulation of MEF2 target genes. Transfection of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 replaced by Ala259/Ala498, HDAC5-S/A), resulted in resistance to ketamine-induced nuclear export, suppression of ketamine-mediated MEF2 transcriptional activity, and decreased expression of MEF2 target genes. Behaviorally, viral-mediated hippocampal knockdown of HDAC5 blocked or occluded the antidepressant effects of ketamine both in unstressed and stressed animals. Taken together, our results reveal a novel role of HDAC5 in the actions of ketamine and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of ketamine. PMID:26647181

  11. Antidepressant-like effect of Tagetes lucida Cav. extract in rats: involvement of the serotonergic system.

    Science.gov (United States)

    Gabriela, Guadarrama-Cruz; Javier, Alarcón-Aguilar Francisco; Elisa, Vega-Avila; Gonzalo, Vázquez-Palacios; Herlinda, Bonilla-Jaime

    2012-01-01

    It has been demonstrated that the decoction of the aerial parts of Tagetes lucida Cav. produces an antidepressant effect during the forced swimming test (FST) in rats. The aim of this study was to evaluate the effect of different organic extracts and one aqueous extract of the aerial parts of T. lucida on the FST. In addition, the possible involvement of the serotonergic system in the antidepressant-like effect of T. lucida in the FST was evaluated, as was its potential toxicological effect. The different extracts of T. lucida (methanol, hexane, dichloromethane and aqueous, 10 and 50 mg/kg), as well as fluoxetine (FLX, 5 mg/kg), were administered per os (p.o.) to rats for 14 days. All animals were subjected to the FST. Only the aqueous extract of T. lucida at a dose of 50 mg/kg significantly reduced immobility behavior and increased swimming in the FST, similar to FLX. Later, the aqueous extract of T. lucida (50mg/kg) was administered for 1, 7 and 14 days. An antidepressant effect was observed after 7 days of treatment. To evaluate the participation of the serotoninergic system, the animals were pretreated with PCPA, an inhibitor of serotonin synthesis (100 mg/kg/day for 4 consecutive days). The animals were treated with the aqueous extract of T. lucida (50 mg/kg) and FLX (5 mg/kg) 24 h after the final injection and were then subjected to the FST. Pretreatment with PCPA inhibited the antidepressant effect of both T. lucida and FLX. Finally, T. lucida was administered p.o. and intraperitoneal route to evaluate its acute toxicological effect. The aqueous extract of T. lucida, administered p.o., did not produce lethality or any significant changes in behavior. In conclusion, the aqueous extract of T. lucida manifested an antidepressant-like effect in the FST mediated by the serotonergic system, with no adverse effects when administered p.o.

  12. Magnetic solid phase extraction coupled with desorption corona beam ionization-mass spectrometry for rapid analysis of antidepressants in human body fluids.

    Science.gov (United States)

    Chen, Di; Zheng, Hao-Bo; Huang, Yun-Qing; Hu, Yu-Ning; Yu, Qiong-Wei; Yuan, Bi-Feng; Feng, Yu-Qi

    2015-08-21

    Ambient ionization techniques show good potential in rapid analysis of target compounds. However, a direct application of these ambient ionization techniques for the determination of analytes in a complex matrix is difficult due to the matrix interference and ion suppression. To resolve this problem, here we developed a strategy by coupling magnetic solid phase extraction (MSPE) with desorption corona beam ionization (DCBI)-mass spectrometry (MS). As a proof of concept, the pyrrole-coated Fe3O4 magnetic nanoparticles (Fe3O4@Ppy) were prepared and used for the extraction of antidepressants. After extraction, the Fe3O4@Ppy with trapped antidepressants was then directly subjected to DCBI-MS analysis with the aid of a homemade magnetic glass capillary. As the MSPE process is rapid and the direct DCBI-MS analysis does not need solvent desorption or chromatographic separation processes, the overall analysis can be completed within 3 min. The proposed MSPE-DCBI-MS method was then successfully used to determine antidepressants in human urine and plasma. The calibration curves were obtained in the range of 0.005-0.5 μg mL(-1) for urine and 0.02-1 μg mL(-1) for plasma with reasonable linearity (R(2) > 0.951). The limits of detection of three antidepressants were in the range of 0.2-1 ng mL(-1) for urine and 2-5 ng mL(-1) for plasma. Acceptable reproducibility for rapid analysis was achieved with relative standard deviations less than 19.1% and the relative recoveries were 85.2-118.7%. Taken together, the developed MSPE-DCBI-MS strategy offers a powerful capacity for rapid analysis of target compounds in a complex matrix, which would greatly expand the applications of ambient ionization techniques with plentiful magnetic sorbents.

  13. The effect of knowledge and expectations on adherence to and persistence with antidepressants

    Directory of Open Access Journals (Sweden)

    Woodward SC

    2016-05-01

    Full Text Available Sophie Claire Woodward, Bonnie Jayne Bereznicki, Juanita Louise Westbury, Luke Ryan Elliot Bereznicki Pharmacy, School of Medicine, University of Tasmania, Hobart, TAS, Australia Purpose: Adherence to and persistence with antidepressants are often suboptimal. However, little is known about how patient knowledge and outcome expectations may influence antidepressant adherence and persistence.Method: Individuals who had been prescribed their first antidepressant to treat depression in the preceding 6 months were recruited to an online survey via Facebook. Knowledge, education received, and initial outcome expectations were analyzed for associations with persistence and adherence.Results: Two hundred and twenty surveys were analyzed. A total of 117 participants had taken their antidepressant for at least 3 months; another 25 had never started or stopped after <3 months without consulting their doctor. Differences in expectations and various educational messages among persistent and nonpersistent participants were identified. Having received the instruction “don’t stop it without checking with your doctor” was a significant independent predictor of persistence (odds ratio [OR] =5.9, 95% confidence interval [CI] =1.4–24.5. At the time of the survey, 82.7% of participants were taking an antidepressant and 77.9% were adherent. Significant independent predictors of adherence were a greater age (OR =1.1, 95% CI =1.0–1.2, knowledge (OR =1.6, 95% CI =1.1–2.3, being informed of common side effects (OR =5.5, 95% CI =1.1–29.0, and having discussed ways to solve problems (OR =3.9, 95% CI =1.1–14.5.Conclusion: Improving outcome expectations and particular educational messages may increase adherence and persistence. Greater knowledge may enhance adherence. Further investigation is warranted to determine whether a focus on these simple educational messages will improve outcomes in patients who commence an antidepressant.Keywords: counseling

  14. The effect of knowledge and expectations on adherence to and persistence with antidepressants.

    Science.gov (United States)

    Woodward, Sophie Claire; Bereznicki, Bonnie Jayne; Westbury, Juanita Louise; Bereznicki, Luke Ryan Elliot

    2016-01-01

    Adherence to and persistence with antidepressants are often suboptimal. However, little is known about how patient knowledge and outcome expectations may influence antidepressant adherence and persistence. Individuals who had been prescribed their first antidepressant to treat depression in the preceding 6 months were recruited to an online survey via Facebook. Knowledge, education received, and initial outcome expectations were analyzed for associations with persistence and adherence. Two hundred and twenty surveys were analyzed. A total of 117 participants had taken their antidepressant for at least 3 months; another 25 had never started or stopped after <3 months without consulting their doctor. Differences in expectations and various educational messages among persistent and nonpersistent participants were identified. Having received the instruction "don't stop it without checking with your doctor" was a significant independent predictor of persistence (odds ratio [OR] =5.9, 95% confidence interval [CI] =1.4-24.5). At the time of the survey, 82.7% of participants were taking an antidepressant and 77.9% were adherent. Significant independent predictors of adherence were a greater age (OR =1.1, 95% CI =1.0-1.2), knowledge (OR =1.6, 95% CI =1.1-2.3), being informed of common side effects (OR =5.5, 95% CI =1.1-29.0), and having discussed ways to solve problems (OR =3.9, 95% CI =1.1-14.5). Improving outcome expectations and particular educational messages may increase adherence and persistence. Greater knowledge may enhance adherence. Further investigation is warranted to determine whether a focus on these simple educational messages will improve outcomes in patients who commence an antidepressant.

  15. Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

    NARCIS (Netherlands)

    Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

    2014-01-01

    Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

  16. The effect of prolonged duration of untreated depression on antidepressant treatment outcome

    DEFF Research Database (Denmark)

    Bukh, Jens Otto Drachmann; Bock, Camilla; Vinberg, Maj

    2013-01-01

    The duration of untreated illness has been considered a likely predictor of the course of psychotic disorders. However, there is only sparse data concerning the influence of treatment delay on the outcome of mood disorders. The present study aimed to assess the effect of prolonged untreated...... depression on the outcome of antidepressant treatment....

  17. Drug dose as mediator of treatment effect in antidepressant drug trials: the case of fluoxetine.

    Science.gov (United States)

    Purgato, M; Gastaldon, C; Papola, D; Magni, L R; Rossi, G; Barbui, C

    2015-06-01

    This study aimed at investigating whether dose is a mediator of treatment effect in fluoxetine-randomized trials. Specifically, we investigated whether dose was higher in trials in which the aim was to demonstrate fluoxetine efficacy in comparison with older antidepressants and lower in trials in which the aim was to demonstrate a new drug's efficacy against fluoxetine. We applied the model developed by Baron and Kenny to investigate the mediational role of drug dose on treatment effect. We included all randomized controlled trials comparing fluoxetine with other antidepressants as monotherapy in the acute-phase treatment of unipolar major depression. A total of 173 studies were included. In 76 comparisons (44%), fluoxetine was the experimental antidepressant. A metaregression analysis indicated that after adjusting for possible confounders, studies where fluoxetine was the experimental agent were associated with a significant advantage for fluoxetine. However, the Baron and Kenny model revealed no mediational role of drug dose in influencing treatment effect. The outcome of fluoxetine-randomized trials changed according to whether this drug was used as a new compound or as a reference. This finding cannot be attributed to antidepressants dose, as dose failed to emerge as mediator of treatment effect in the Baron and Kenny approach. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Does good leadership buffer effects of high emotional demands at work on risk of antidepressant treatment?

    DEFF Research Database (Denmark)

    Madsen, Ida E H; Hanson, Linda L Magnusson; Rugulies, Reiner Ernst

    2014-01-01

    Emotionally demanding work has been associated with increased risk of common mental disorders. Because emotional demands may not be preventable in certain occupations, the identification of workplace factors that can modify this association is vital. This article examines whether effects of emoti...... of emotional demands on antidepressant treatment, as an indicator of common mental disorders, are buffered by good leadership....

  19. Study On The Anti-Depressant Effect Of Chaihu Guizhi Decoction ...

    African Journals Online (AJOL)

    shorten immobility time of mice in the tail suspension test, after administration of 50, 100, and 200mg/kg, Chaihu Guizhi decoction, a significant dose-dependent antagonism of reserpine-induced hypothermia was observed in mice of each treatment group. Conclusion: Chaihu Guizhi decoction has an antidepressant effect.

  20. Evidence for the involvement of opioid system in the antidepressant-like effect of ascorbic acid.

    Science.gov (United States)

    Moretti, Morgana; Ribeiro, Camille M; Neis, Vivian B; Bettio, Luis Eduardo B; Rosa, Priscila B; Rodrigues, Ana Lúcia S

    2018-02-01

    Considering the involvement of the opioid system in major depressive disorder (MDD), mainly concerning refractory MDD, and the evidence that ascorbic acid may exert a beneficial effect for the treatment of this disorder, this study investigated the involvement of the opioid system in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST). Treatment of Swiss mice with the non-selective opioid receptor antagonist naloxone (1 mg/kg, i.p.) prevented the reduced immobility time caused by ascorbic acid (1 mg/kg, p.o.) in the TST. Additionally, administration of the selective μ1-opioid receptor antagonist, naloxonazine (10 mg/kg, i.p.), also abolished the antidepressant-like action of the same dose of ascorbic acid in the TST. We also investigated the possible relationship between the opioid system and NMDA receptors in the mechanism of action of ascorbic acid or ketamine (0.1 mg/kg, i.p.) in the TST. Treatment of mice with naloxone (1 mg/kg, i.p.) blocked the synergistic antidepressant-like effect of ascorbic acid (0.1 mg/kg. p.o.) and MK-801 (0.001 mg/kg, p.o., a non-competitive NMDA receptor antagonist) in the TST. Combined administration of ketamine and MK-801 induced a synergistic antidepressant-like action, and naloxone partially abolished this effect. Our results indicate that the antidepressant-like effect of ascorbic acid in the TST appears to be dependent on the activation of the opioid system, especially μ1-opioid receptors, which might be an indirect consequence of NMDA receptor inhibition elicited by ascorbic acid administration.

  1. Antidepressant-like effects of methanol extract of Hibiscus tiliaceus flowers in mice

    Directory of Open Access Journals (Sweden)

    Vanzella Cláudia

    2012-04-01

    Full Text Available Abstract Background Hibiscus tiliaceus L. (Malvaceae is used in postpartum disorders. Our purpose was to examine the antidepressant, anxiolytic and sedative actions of the methanol extract of H. tiliaceus flowers using animal models. Methods Adult male Swiss albino mice were treated with saline, standard drugs or methanol extract of H. tiliaceus and then subjected to behavioral tests. The forced swimming and tail suspension tests were used as predictive animal models of antidepressant activity, where the time of immobility was considered. The animals were submitted to the elevated plus-maze and ketamine-induced sleeping time to assess anxiolytic and sedative activities, respectively. Results Methanol extract of H. tiliaceus significantly decreased the duration of immobility in both animal models of antidepressant activity, forced swimming and tail suspension tests. This extract did not potentiate the effect of ketamine-induced hypnosis, as determined by the time to onset and duration of sleeping time. Conclusion Our results indicate an antidepressant-like profile of action for the extract of Hibiscus tiliaceus without sedative side effect.

  2. Requirement of AMPK activation for neuronal metabolic-enhancing effects of antidepressant paroxetine.

    Science.gov (United States)

    Jeong, Jihyeon; Park, Minsun; Yoon, Jeong Seon; Kim, Hyunjeong; Lee, Su Kyoung; Lee, Eun; Namkoong, Kee; Kim, Eosu

    2015-05-06

    Reduced glucose metabolism has been implicated as a pathophysiology of depressive disorder. Normalization of such impaired neurometabolism has been related to the therapeutic actions of antidepressant medication. However, the molecular mechanism underlying the neurometabolic actions of antidepressants has not been fully understood. Given that AMP-activated protein kinase (AMPK) is a master switch for energy homeostasis, we aimed to determine whether selective serotonin reuptake inhibitor paroxetine enhances energy metabolism by activating AMPK in neuroblastoma cells. We found that paroxetine dose dependently increased mitochondrial biogenesis, which involves the AMPK-peroxisome proliferator-activated receptor-γ coactivator-1α pathway. In addition, paroxetine-induced AMPK activation increases glucose uptake and ATP production. These neurometabolic effects of paroxetine were suppressed by cotreatment with compound C (CC), an AMPK inhibitor. These findings suggest a possibility that modulation of the AMPK pathway might be a previously unrecognized mechanism underlying the neurometabolic action of antidepressants. Further study is warranted to examine the region-specific and time-specific effects of AMPK modulation by antidepressants on mood-related behaviors.

  3. The Effect of False-positive Mammograms on Antidepressant and Anxiolytic Initiation.

    Science.gov (United States)

    Segel, Joel E; Balkrishnan, Rajesh; Hirth, Richard A

    2017-08-01

    Despite reported increases in anxiety following a false-positive mammogram, there is little evidence the effect rises to the clinical level of initiating medication. To analyze the effect of a false-positive mammogram on antidepressant or anxiolytic initiation and identify subpopulations most at risk. MarketScan commercial and Medicaid claims databases used to identify women ages 40-64 undergoing screening mammography with no prior antidepressant or anxiolytic claims. Using a retrospective cohort design, we estimated the effects of a false-positive relative to a negative mammogram on the likelihood of initiating antidepressants or anxiolytics using multivariate logistic models estimated separately by insurance type. At 3 months after a false-positive mammogram, the relative risk (RR) for antidepressant or anxiolytic initiation was 1.19 [95% confidence interval (CI), 1.06-1.31] for the commercially insured and 1.13 (95% CI, 0.96-1.29) in the Medicaid population. In addition, 4 subgroups were at particularly elevated risk: commercially insured women ages 40-49 (RR=1.33; 95% CI, 1.13-1.54) or whose false-positive required multiple tests to resolve (RR=1.37; 95% CI, 1.17-1.57), included a biopsy (RR=1.68; 95% CI, 1.18-2.17), or whose resolution took >1 week (RR=1.21; 95% CI, 1.07-1.34). False-positive mammograms were associated with significant increases in antidepressant or anxiolytic imitation among the commercially insured. Follow-up resources may be particularly beneficial for cases taking longer to resolve and involving biopsies or multiple tests. The results highlight the need to resolve false-positives quickly and effectively and to monitor depressive symptoms following a positive result.

  4. Anxiolytic and antidepressive effects of magnesium in rats and their effect on general behavioural parameters

    Directory of Open Access Journals (Sweden)

    Samardžić Janko

    2011-01-01

    Full Text Available Magnesium (Mg is an essential element that catalyses more than 300 enzyme systems. Its effects on the central nervous system are exhibited through the blocking of activity of N-methyl D-aspartat (NMDA receptors and potentiating of GABA-ergic neurotransmission. Due to the vast importance of these two neurotransmission systems in the fine regulation of the central integrative function activity, the aim of this research was to test the anxiolytic and antidepressive effects of magnesium, after acute and repeated application, and its influence on general behavioural parameters. In this research Wistar albino rats were treated with increasing doses of Mg chloride 6-hydrate (MgCl 10, 20, 30 mg/kg. In order to determine anxiolytic and antidepressive properties of magnesium two models were used: elevated plus maze (EPM and forced swim test (FST. Behavioural parameters (stillness and mobility were recorded during acute and repeated administration of the active substance. Results of EPM testing showed no significant difference between groups, p>0.05. After acute application of increasing doses of magnesium chloride hydrate in FST, we showed the statistically significant difference in immobility time between the group of animals treated with Mg and the control group treated with the solvent, p<0.01. The statistically significant difference between groups treated with the lowest and the middle dose of magnesium and the controls was observed already on the first day of examining behavioural parameters (p=0.020, p=0.010. Our research has showed that magnesium, following acute administration, increases locomotor activity, and has an antidepressive but not an anxiolytic effect.

  5. Neural plasticity and proliferation in the generation of antidepressant effects: hippocampal implication.

    Science.gov (United States)

    Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Díaz, Alvaro; Castro, Elena; dos Anjos, Severiano; Pascual-Brazo, Jesús; Linge, Raquel; Vargas, Veronica; Blanco, Helena; Martínez-Villayandre, Beatriz; Pazos, Ángel; Valdizán, Elsa M

    2013-01-01

    It is widely accepted that changes underlying depression and antidepressant-like effects involve not only alterations in the levels of neurotransmitters as monoamines and their receptors in the brain, but also structural and functional changes far beyond. During the last two decades, emerging theories are providing new explanations about the neurobiology of depression and the mechanism of action of antidepressant strategies based on cellular changes at the CNS level. The neurotrophic/plasticity hypothesis of depression, proposed more than a decade ago, is now supported by multiple basic and clinical studies focused on the role of intracellular-signalling cascades that govern neural proliferation and plasticity. Herein, we review the state-of-the-art of the changes in these signalling pathways which appear to underlie both depressive disorders and antidepressant actions. We will especially focus on the hippocampal cellularity and plasticity modulation by serotonin, trophic factors as brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) through intracellular signalling pathways-cAMP, Wnt/ β -catenin, and mTOR. Connecting the classic monoaminergic hypothesis with proliferation/neuroplasticity-related evidence is an appealing and comprehensive attempt for improving our knowledge about the neurobiological events leading to depression and associated to antidepressant therapies.

  6. The effects of antidepressants and pilocarpine on rat parotid glands: an immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Tatiana Maria Folador Mattioli

    2011-01-01

    Full Text Available OBJECTIVES: To evaluate the effects of antidepressants and pilocarpine on the quantity of myoepithelial cells and on the proliferation index of the epithelial cells of rat parotid glands. INTRODUCTION: Hyposalivation, xerostomia, and alterations in saliva composition are important clinical side effects related to the use of antidepressants. METHODS: Ninety male Wistar rats were allocated to nine groups. The control groups received saline for 30 (group C30 or 60 days (group C60 or pilocarpine for 60 days (group Pilo. The experimental groups were administered fluoxetine (group F30 or venlafaxine for 30 days (group V30; fluoxetine (group FS60 or venlafaxine (group VS60 with saline for 60 days; or fluoxetine (group FP60 or venlafaxine (group VP60 with pilocarpine for 60 days. Parotid gland specimens were processed, and the immunohistochemical expression of calponin and proliferating cell nuclear anti-antigen on the myoepithelial and parenchymal cells, respectively, was evaluated. Analysis of variance (ANOVA, Tukey HSD and Games-Howell tests were applied to detect differences among groups (p<0.05. RESULTS: Compared with the controls, chronic exposure to antidepressants was associated with an increase in the number of positively stained cells for calponin. In addition, venlafaxine administration for 30 days was associated with an increase in the number of positively stained cells for proliferating cell nuclear anti-antigen. Fluoxetine and pilocarpine (group FP60 induced a significant decrease in the number of positively stained cells for calponin compared with all other groups. CONCLUSIONS: The number of positively stained cells for calponin increased after chronic administration of antidepressants. The proliferation index of the epithelial cells of rat parotid glands was not altered by the use of antidepressants for 60 days.

  7. Divorce and subsequent increase in uptake of antidepressant medication: a Finnish registry-based study on couple versus individual effects.

    Science.gov (United States)

    Monden, Christiaan W S; Metsä-Simola, Niina; Saarioja, Saska; Martikainen, Pekka

    2015-02-19

    There is an average negative mental health effect for individuals who experience divorce. Little is known whether the pattern of such divorce effects varies within couples. We study whether the husband and wife experience similar harmful effects of divorce, whether they experience opposite effects, or whether divorce effects are purely individual. We use Finnish registry data to compare changes over a period of 5 years in antidepressant use of husbands and wives from 4,558 divorcing couples to 108,637 continuously married pairs aged 40-64, all of whom were healthy at baseline. In the period three years before and after divorce antidepressant use increases substantially. However, the likelihood of uptake of antidepressant medication during this process of divorce by one partner appears to be independent of medication uptake in the other partner. In contrast, among continuously married couples there is a clear pattern of convergence: If one partner starts to use antidepressants this increases the likelihood of uptake of antidepressant medication in the other partner. Our findings suggest that divorce effects on antidepressant use are individual and show no pattern of either convergence or divergence at the level of the couple. The increased incidence of antidepressant use associated with divorce occurs in individuals independent of what happens to their ex-partner.

  8. Mechanistic Target of Rapamycin-Independent Antidepressant Effects of (R)-Ketamine in a Social Defeat Stress Model.

    Science.gov (United States)

    Yang, Chun; Ren, Qian; Qu, Youge; Zhang, Ji-Chun; Ma, Min; Dong, Chao; Hashimoto, Kenji

    2018-01-01

    The role of the mechanistic target of rapamycin (mTOR) signaling in the antidepressant effects of ketamine is controversial. In addition to mTOR, extracellular signal-regulated kinase (ERK) is a key signaling molecule in prominent pathways that regulate protein synthesis. (R)-Ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here we investigated whether mTOR signaling and ERK signaling play a role in the antidepressant effects of two enantiomers. The effects of mTOR inhibitors (rapamycin and AZD8055) and an ERK inhibitor (SL327) on the antidepressant effects of ketamine enantiomers in the chronic social defeat stress (CSDS) model (n = 7 or 8) and on those of ketamine enantiomers in these signaling pathways in mouse brain regions were examined. The intracerebroventricular infusion of rapamycin or AZD8055 blocked the antidepressant effects of (S)-ketamine, but not (R)-ketamine, in the CSDS model. Furthermore, (S)-ketamine, but not (R)-ketamine, significantly attenuated the decreased phosphorylation of mTOR and its downstream effector, ribosomal protein S6 kinase, in the prefrontal cortex of susceptible mice after CSDS. Pretreatment with SL327 blocked the antidepressant effects of (R)-ketamine but not (S)-ketamine. Moreover, (R)-ketamine, but not (S)-ketamine, significantly attenuated the decreased phosphorylation of ERK and its upstream effector, mitogen-activated protein kinase/ERK kinase, in the prefrontal cortex and hippocampal dentate gyrus of susceptible mice after CSDS. This study suggests that mTOR plays a role in the antidepressant effects of (S)-ketamine, but not (R)-ketamine, and that ERK plays a role in (R)-ketamine's antidepressant effects. Thus, it is unlikely that the activation of mTOR signaling is necessary for antidepressant actions of (R)-ketamine. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?

    Directory of Open Access Journals (Sweden)

    Ioannidis John PA

    2008-05-01

    Full Text Available Abstract Antidepressants, in particular newer agents, are among the most widely prescribed medications worldwide with annual sales of billions of dollars. The introduction of these agents in the market has passed through seemingly strict regulatory control. Over a thousand randomized trials have been conducted with antidepressants. Statistically significant benefits have been repeatedly demonstrated and the medical literature is flooded with several hundreds of "positive" trials (both pre-approval and post-approval. However, two recent meta-analyses question this picture. The first meta-analysis used data that were submitted to FDA for the approval of 12 antidepressant drugs. While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits. A second meta-analysis using also FDA-submitted data examined the relationship between treatment effect and baseline severity of depression. Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinically important only in the very small minority of patient populations with severe major depression. In severe major depression, antidepressants did not become more effective, simply placebo lost effectiveness. These data suggest that antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied. I discuss how the use of many small randomized trials with clinically non-relevant outcomes, improper interpretation of statistical significance, manipulated study design, biased selection of study populations, short follow-up, and selective and distorted

  10. The antidepressant effect of an antiulcer pentadecapeptide BPC 157 in Porsolt's test and chronic unpredictable stress in rats. A comparison with antidepressants.

    Science.gov (United States)

    Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Marovic, A; Prkacin, I; Duplancic, B; Zoricic, I; Aralica, G; Lovric-Bencic, M; Ziger, T; Perovic, D; Rotkvic, I; Mise, S; Hanzevacki, M; Hahn, V; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R

    2000-01-01

    Various antidepressants have antiulcer activity. Likewise, the models currently used in ulcers and depression disorders research have a considerable degree of similarity. Therefore, the possibility that depression disorders could be effectively influenced by a primary antiulcer agent with a cyto/organoprotective activity, such as the novel stomach pentadecapeptide BPC 157, was investigated in two rat depression assays. First, a forced swimming test (a Porsolt's procedure) was used. As a more severe procedure, chronic unpredictable stress (after 5 d of unpredictable stress protocol, once daily drug application during stress procedure, open field-immobility test assessment at fourth or sixth day of medication) was used. In a forced swimming test, a reduction of the immobility time in BPC 157 (10 microg, 10 ng x kg(-1) i.p.) treated rats corresponds to the activity of the 15 mg or 40 mg (i.p.) of conventional antidepressants, imipramine or nialamide, respectively, given according to the original Porsolt's protocol. In chronic unpredictable stress procedure, particular aggravation of experimental conditions markedly affected the conventional antidepressant activity, whereas BPC 157 effectiveness was continuously present. The effect of daily imipramine (30 mg) medication could be seen only after a more prolonged period, but not after a shorter period (i.e., 4-d protocol). In these conditions, no delay in the effectiveness was noted in BPC 157 medication and a reduction of the immobility of chronically stressed rats was noted after both 4 and 6 d of BPC 157 (10 microg, 10 ng) medication.

  11. The Anxiolytic and Antidepressant-like Effects of Testosterone and Estrogen in Gonadectomized Male Rats.

    Science.gov (United States)

    Carrier, Nicole; Saland, Samantha K; Duclot, Florian; He, Huan; Mercer, Roger; Kabbaj, Mohamed

    2015-08-15

    While the influence of testosterone levels on vulnerability to affective disorders is not straightforward, research suggests this hormone may confer some degree of resiliency in men. We recently demonstrated a role for the dentate gyrus in mediating testosterone's protective effects on depressive-like behavior in gonadectomized male rats. Here, testosterone may exert its effects through androgen receptor-mediated mechanisms or via local aromatization to estradiol. Gonadectomized male rats were implanted with a placebo, testosterone, or estradiol pellet, and subsequent protective anxiolytic- and antidepressant-like effects of testosterone and its aromatized metabolite, estradiol, were then investigated in the open field and sucrose preference tests, respectively. Moreover, their influence on gene expression in the hippocampus was analyzed by genome-wide complementary DNA microarray analysis. Finally, the contribution of testosterone's aromatization within the dentate gyrus was assessed by local infusion of the aromatase inhibitor fadrozole, whose efficacy was confirmed by liquid chromatography-tandem mass spectrometry. Both hormones had antidepressant-like effects associated with a substantial overlap in transcriptional regulation, particularly in synaptic plasticity- and mitogen-activated protein kinase pathway-related genes. Further, chronic aromatase inhibition within the dentate gyrus blocked the protective effects of testosterone. Both testosterone and estradiol exhibit anxiolytic- and antidepressant-like effects in gonadectomized male rats, while similarly regulating critical mediators of these behaviors, suggesting common underlying mechanisms. Accordingly, we demonstrated that testosterone's protective effects are mediated, in part, by its aromatization in the dentate gyrus. These findings thus provide further insight into a role for estradiol in mediating the protective anxiolytic- and antidepressant-like effects of testosterone. Copyright © 2015 Society

  12. Antidepressant effects of total tertiary alkaloid fraction of Cissampelos sympodialis Eichler in rodents

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    Sueli Mendonça-Netto

    Full Text Available The purpose of the present study was to evaluate the effects of total tertiary alkaloid fraction (TTAF of Cissampelos sympodialis Eichler (Menispermaceae on two animal models of depression: a forced swim test and b reserpine test. Treatment of mice with TTAF (12.5 mg/kg reduced the total immobility time. It also reversed the reserpine-induced hypothermia, demonstrating an antidepressant effect in both models. Additionally, TTAF treatment did not modify the ambulation and rearing evaluated in open field test in order to investigate if the immobility time reduction found in the forced swimming test was caused by locomotive activity stimulation. Since warifteine is one of the main alkaloids present in the TTAF of C. sympodialis, and it has inhibitory activity of the phosphodiesterase enzyme, it may be responsible by the antidepressant effect found in the fraction studied.

  13. Antidepressant, psychostimulant, and nootropic effects of major and trace element composition.

    Science.gov (United States)

    Afanasieva, O G; Suslov, N I; Shilova, I V

    2013-06-01

    The antidepressant, psychostimulant, and nootropic effects of a composition of major and trace elements including KCl, RbNO3, magnesium sulfate, and zinc sulfate were studied on the models of behavioural despair (Porsolt test) and conditioned passive avoidance test. The preparation was found to shorten the immobilization time in the Porsolt test and promote retention of the conditioned passive avoidance. The most pronounced psychostimulant effect of the substance was observed at a dose of 4.68 mg/kg and the most pronounced antidepressant effect was found at a dose of 18.72 mg/kg. Maximum nootropic activity of the preparation was found at a dose of 93.6 mg/kg.

  14. Antidepressants and Suicidal Ideation in Adolescence: A Paradoxical Effect

    Science.gov (United States)

    Pierson, Eric E.

    2009-01-01

    The past two decades have seen a rapid increase in the number and types of psychopharmacological medications that are available for the treatment of depression in children and adolescents. Parents and adolescents often raise questions as to the potential increase in suicidal ideation associated with the use of primarily selective serotonin…

  15. Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors

    Science.gov (United States)

    Zanelati, TV; Biojone, C; Moreira, FA; Guimarães, FS; Joca, SRL

    2010-01-01

    Background and purpose: Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT1A receptors. As 5-HT1A receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT1A receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF). Experimental approach: Male Swiss mice were given (i.p.) CBD (3, 10, 30, 100 mg·kg−1), imipramine (30 mg·kg−1) or vehicle and were submitted to the forced swimming test or to an open field arena, 30 min later. An additional group received WAY100635 (0.1 mg·kg−1, i.p.), a 5-HT1A receptor antagonist, before CBD (30 mg·kg−1) and assessment by the forced swimming test. BDNF protein levels were measured in the hippocampus of another group of mice treated with CBD (30 mg·kg−1) and submitted to the forced swimming test. Key results: CBD (30 mg·kg−1) treatment reduced immobility time in the forced swimming test, as did the prototype antidepressant imipramine, without changing exploratory behaviour in the open field arena. WAY100635 pretreatment blocked CBD-induced effect in the forced swimming test. CBD (30 mg·kg−1) treatment did not change hippocampal BDNF levels. Conclusion and implications: CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT1A receptors. PMID:20002102

  16. The analgesic effect of different antidepressants combined with aspirin on thermally induced pain in Albino mice

    Directory of Open Access Journals (Sweden)

    Abdalla S. Elhwuegi

    2012-04-01

    Full Text Available Background:Combination analgesics provide more effective pain relief for a broader spectrum of pain. This research examines the possible potentiation of the analgesic effect of different classes of antidepressants when combined with aspirin in thermal model of pain using Albino mice.Methods:Different groups of six animals each were injected intraperitoneally by different doses of aspirin (50, 100, or 200 mg/kg, imipramine (2.5, 7.5, 15 or 30 mg/kg, fluoxetine (1.25, 2.5, 5 or 7.5 mg/kg, mirtazapine (1.25, 2.5, or 5 mg/kg and a combination of a fixed dose of aspirin (100 mg/kg with the different doses of the three antidepressants. One hour later the analgesic effect of these treatments were evaluated against thermally induced pain. All data were subjected to statistical analysis using unpaired Student's t-test.Results:Aspirin had no analgesic effect in thermally induced pain. The three selected antidepressants produced dose dependent analgesia. The addition of a fixed dose of aspirin to imipramine significantly increased the reaction time (RT of the lowest dose (by 23% and the highest dose (by 20%. The addition of the fixed dose of aspirin to fluoxetine significantly increased RT by 13% of the dose 2.5 mg/Kg. Finally, the addition of the fixed dose of aspirin significantly potentiated the antinociceptive effect of the different doses of mirtazapine (RT was increased by 24, 54 and 38% respectively.Conclusion:Combination of aspirin with an antidepressant might produce better analgesia, increasing the efficacy of pain management and reduces side effects by using smaller doses of each drug.

  17. Comparison of antidepressant-like and abuse-related effects of phencyclidine in rats.

    Science.gov (United States)

    Hillhouse, Todd M; Porter, Joseph H; Negus, S Stevens

    2014-12-01

    Preclinical Research N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine, have emerged as novel candidate treatments for major depressive disorder, but abuse potential of these agents is a concern. The NMDA antagonist phencyclidine has known abuse liability but undefined efficacy as an antidepressant. To further evaluate the relationship between antidepressant-like and abuse-related effects of NMDA antagonists, this study evaluated the effects of phencyclidine (1.0-10.0 mg/kg) in male Sprague-Dawley rats responding under two procedures that have been used to assess antidepressant-like effects (differential-reinforcement-of-low-rate [DRL] 72 s schedule of food reinforcement; n = 9) and abuse-related drug effects (intracranial self-stimulation [ICSS]; n = 6). Under the DRL 72 s schedule, phencyclidine (10.0 mg/kg) increased reinforcers and decreased responses without shifting the peak location of the interresponse time (IRT) distribution. Ketamine (10.0 mg/kg) also increased reinforcers and decreased responses, but unlike phencyclidine, it produced a rightward shift in the peak location of the IRT distribution. The 10.0 mg/kg phencyclidine dose that decreased DRL 72 s responding also decreased rates of ICSS for 50 min after its administration; however, abuse-related ICSS facilitation was observed at later times (100-300 min) or after a lower phencyclidine dose (3.2 mg/kg). These results suggest that phencyclidine produces weaker antidepressant-like effects, but stronger abuse-related effects than ketamine in these procedures. © 2014 Wiley Periodicals, Inc.

  18. Enhanced cognitive function and antidepressant-like effects after krill oil supplementation in rats.

    Science.gov (United States)

    Wibrand, Karin; Berge, Kjetil; Messaoudi, Michaël; Duffaud, Anaïs; Panja, Debabrata; Bramham, Clive R; Burri, Lena

    2013-01-25

    The purpose of the study was to evaluate the effects of krill oil (KO) on cognition and depression-like behaviour in rats. Cognition was assessed using the Aversive Light Stimulus Avoidance Test (ALSAT). The Unavoidable Aversive Light Stimulus (UALST) and the Forced Swimming Test (FST) were used to evaluate the antidepressant-like effects of KO. Imipramine (IMIP) was used as the antidepressant reference substance. After 7 weeks of KO intake, both males and females treated with KO were significantly better in discriminating between the active and the inactive levers in the ALSAT from day 1 of training (p<0.01). Both KO and IMIP prevented resignation/depression on the third day in the UALST. Similarly, a shorter immobility time was observed for the KO and IMIP groups compared to the control in the FST (p<0.001). These data support a robust antidepressant-like potential and beneficial cognitive effect of KO. Changes in expression of synaptic plasticity-related genes in the prefrontal cortex and hippocampus were also investigated. mRNA for brain-derived neurotrophic factor (Bdnf) was specifically upregulated in the hippocampus of female rats receiving 7 weeks of KO supplementation (p=0.04) and a similar trend was observed in males (p=0.08). Males also exhibited an increase in prefrontal cortex expression of Arc mRNA, a key protein in long-term synaptic plasticity (p=0.05). IMIP induced clear effects on several plasticity related genes including Bdnf and Arc. These results indicate that active components (eicosapentaenoic acid, docosahexaenoic acid and astaxanthin) in KO facilitate learning processes and provide antidepressant-like effects. Our findings also suggest that KO might work through different physiological mechanisms than IMIP.

  19. Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects in Olfactory Bulbectomized Mice.

    Science.gov (United States)

    Matsui, Nobuaki; Akae, Haruka; Hirashima, Nana; Kido, Yuki; Tanabe, Satoshi; Koseki, Mayumi; Fukuyama, Yoshiyasu; Akagi, Masaaki

    2016-11-01

    Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain-derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein after 3 h. The present data indicate that magnolol exerts antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Neurogenesis-independent antidepressant-like effects of enriched environment is dependent on adiponectin.

    Science.gov (United States)

    Nicolas, Sarah; Veyssière, Julie; Gandin, Carine; Zsürger, Nicole; Pietri, Mariel; Heurteaux, Catherine; Glaichenhaus, Nicolas; Petit-Paitel, Agnès; Chabry, Joëlle

    2015-07-01

    Environmental enrichment (EE) that combines voluntary physical exercise, sensory and social stimuli, causes profound changes in rodent brain at molecular, anatomical and behavioral levels. Here, we show that EE efficiently reduces anxiety and depression-like behaviors in a mouse model of depression induced by long-term administration of corticosterone. Mechanisms underlying EE-related beneficial effects remain largely unexplored; however, our results point toward adiponectin, an adipocyte-secreted protein, as a main contributor. Indeed, adiponectin-deficient (adipo(-/-)) mice did not benefit from all the EE-induced anxiolytic and antidepressant-like effects as evidenced by their differential responses in a series of behavioral tests. Conversely, a single intravenous injection of exogenous adiponectin restored the sensitivity of adipo(-/-) mice to EE-induced behavioral benefits. Interestingly, adiponectin depletion did not prevent the hippocampal neurogenesis induced by EE. Therefore, antidepressant properties of adiponectin are likely to be related to changes in signaling in the hypothalamus rather than through hippocampal-neurogenesis mechanisms. Additionally, EE did not modify the plasma levels of adiponectin but may favor the passage of adiponectin from the blood to the cerebrospinal fluid. Our findings provide advances in the understanding of the anxiolytic and antidepressant-like effects of EE and highlight adiponectin as a pivotal mediator. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Antidepressant-like effects of Tagetes lucida Cav. in the forced swimming test.

    Science.gov (United States)

    Guadarrama-Cruz, G; Alarcon-Aguilar, F J; Lezama-Velasco, R; Vazquez-Palacios, G; Bonilla-Jaime, H

    2008-11-20

    Tagetes lucida (Asteraceae), has been referred in Mexican traditional medicine for the treatment of different central nervous system (CNS) diseases, mainly depression. Nevertheless, the available scientific information about this species is scarce and there are no reports related to its possible effect on the CNS. In this work, the antidepressant-like effect of extract of Tagetes lucida was evaluated in rats, as well as its potential adverse effects on male sexual behavior (MSB). Antidepressant activity was studied using forced swimming test (FST), motor activity in the open-field test and on MSB in sexually experienced male. The aqueous extract of Tagetes lucida in doses of 5, 10, 50, 100 and 200mg/(kgday)(-1) were administered orally for 14 consecutive days and evaluated on day 14, 2h after the last dose treatment. Fluoxetine (10mg/(kgday)(-1), p.o.) was used as the control positive. The aqueous extract (10, 50, 100mg/(kgday)(-1)) significantly reduced immobility and increased swimming without affecting climbing behavior in the FST. These same doses were not able to modify neither the motor activity nor the MSB. These data indicate that the extract of Tagetes lucida possesses antidepressant-like properties in rats.

  2. Meta-Analysis of the Antidepressant Effects of Acute Sleep Deprivation.

    Science.gov (United States)

    Boland, Elaine M; Rao, Hengyi; Dinges, David F; Smith, Rachel V; Goel, Namni; Detre, John A; Basner, Mathias; Sheline, Yvette I; Thase, Michael E; Gehrman, Philip R

    To provide a quantitative meta-analysis of the antidepressant effects of sleep deprivation to complement qualitative reviews addressing response rates. English-language studies from 1974 to 2016 using the keywords sleep deprivation and depression searched through PubMed and PsycINFO databases. A total of 66 independent studies met criteria for inclusion: conducted experimental sleep deprivation, reported the percentage of the sample that responded to sleep deprivation, provided a priori definition of antidepressant response, and did not seamlessly combine sleep deprivation with other therapies (eg, chronotherapeutics, repetitive transcranial magnetic stimulation). Data extracted included percentage of responders, type of sample (eg, bipolar, unipolar), type of sleep deprivation (eg, total, partial), demographics, medication use, type of outcome measure used, and definition of response (eg, 30% reduction in depression ratings). Data were analyzed with meta-analysis of proportions and a Poisson mixed-effects regression model. The overall response rate to sleep deprivation was 45% among studies that utilized a randomized control group and 50% among studies that did not. The response to sleep deprivation was not affected significantly by the type of sleep deprivation performed, the nature of the clinical sample, medication status, the definition of response used, or age and gender of the sample. These findings support a significant effect of sleep deprivation and suggest the need for future studies on the phenotypic nature of the antidepressant response to sleep deprivation, on the neurobiological mechanisms of action, and on moderators of the sleep deprivation treatment response in depression.

  3. The effects of maternal depression and use of antidepressants during pregnancy on risk of a child small for gestational age

    DEFF Research Database (Denmark)

    Jensen, Hans Mørch; Grøn, Randi; Lidegaard, Ojvind

    2013-01-01

    Use of antidepressants during pregnancy has been associated with an increased rate of children small for gestational age (SGA), but it is unclear whether this is due to an effect of the underlying depressive disorder.......Use of antidepressants during pregnancy has been associated with an increased rate of children small for gestational age (SGA), but it is unclear whether this is due to an effect of the underlying depressive disorder....

  4. [Preliminary screening of biomarkers for curcumin's antidepressant effect based on metabonomics method].

    Science.gov (United States)

    Ma, Zhi-Jie; Zhang, Wei; Dong, Jie-Ming; Yu, Xiao-Hong; Zhao, Xiao-Mei; Pu, Shi-Biao

    2017-09-01

    To screen potential biomarkers of curcumin related to treating depression rats by using metabolomics means, so as to explore the antidepressant action mechanism of curcumin. The healthy male SD rats were randomly divided into four groups. Chronic unpredictable mild stress (CUMS) stimulation was conducted for modeling for 2 weeks, and then curcumin (200 mg•kg⁻¹) or venlafaxine (40 mg•kg⁻¹) was given by gavage administration. The blank group and model group rats were given with the same volume of 1% CMCNa normal saline, once per day for two weeks. The rats serum for each group was collected and LC/MS-IT-TOF method was used to characterize the metabolic differences. Also multivariate statistical analysis was used to screen possible potential biomarkers and analyze the possible metabolic pathways. After administration of curcumin and venlafaxine respectively, the depression indexes of CUMS model rats were all improved significantly (Pcurcumin and venlafaxine groups. In PCA and PLS-DA analysis after curcumin or venlafaxine intervention on CUMS model group rats, the small molecule metabolites level reflects a normal trend, and particularly for the curcumin group. Through metabonomics technology, 11 biomarkers associated with curcumin antidepressant effect were screened, and at the same time seven metabolic pathways were involved. The results showed that curcumin had antidepressant effects, which was evident in both macro and micro levels, comparable with positive drug of venlafaxine. The antidepressant effect of curcumin may be associated with the glycerol phospholipid metabolism, linoleic acid metabolism, pentose and glucuronic acid ester and ether lipid metabolism, but still need further exploration in the future. Copyright© by the Chinese Pharmaceutical Association.

  5. Piperine potentiates the antidepressant-like effect of trans-resveratrol: involvement of monoaminergic system.

    Science.gov (United States)

    Huang, Wu; Chen, Zhuoyou; Wang, Qiandong; Lin, Mengmeng; Wu, Shujuan; Yan, Qizhi; Wu, Fan; Yu, Xuefeng; Xie, Xupei; Li, Gaowen; Xu, Ying; Pan, Jianchun

    2013-12-01

    Major depression is characterized by dysfunction of neuroendocrine and immune networks. Trans-resveratrol, a phenolic compound presented in polygonum cuspidatum, was demonstrated previously to exert antidepressant-like effects through regulating monoaminergic system, oxidative/antioxidant defense and inflammatory response. The present study investigated the synergistic antidepressant-like effect of trans-resveratrol and piperine, a bioavailability enhancer, in mice and explored the possible mechanism. Trans-resveratrol was shown to reduce the immobility time both in the tail suspension and forced swimming tests (TST and FST). But the maximal inhibition was nearly 60% even if the doses were increased by 160 mg/kg; while piperine produced weak antidepressant-like effects in these two models. The interaction between trans-resveratrol and piperine was shown a clear-cut synergistic effect as evidenced by an isobolographic analysis. The further study suggested that the anti-immobility response from the subthreshold dose of piperine (2.5 mg/kg) and low doses of trans-resveratrol (10 and 20 mg/kg) was abolished by pretreatment with para-chlorophenylalanine (PCPA, 300 mg/kg, i.p.) in TST and FST, indicating the involvement of serotonergic system. Moreover, treatment with the subthreshold dose of piperine and low doses of trans-resveratrol attenuated reserpine-induced hypothermia and ptosis arguing for the relevance of noradrenaline. Additional evidence from neurochemical (monoamines in the frontal cortex, hippocampus, and hypothalamus) and biochemical (monoamine oxidase, MAO activity) assays corroborated the synergistically elevated monoaminergic system after co-treatment with trans-resveratrol and piperine. The present results indicate the effect of trans-resveratrol combined with piperine on depressive-like behaviors may be partly due to the potentiated activation of monoaminergic system in the brain. Further studies are necessary to elucidate the involvement of the

  6. Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Chun Yang

    2012-01-01

    Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

  7. Augmentation of antidepressant effects of duloxetine and bupropion by caffeine in mice.

    Science.gov (United States)

    Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu

    2014-09-01

    There is an unmet need in the treatment of depression suggesting requirement of new therapeutic approaches having better efficacy and safety profile. Patients receiving antidepressant therapy generally consume caffeine in the form of tea or coffee. The objective of the present study was to evaluate the augmentation of antidepressant effects of duloxetine and/or bupropion with caffeine. Male Swiss Albino mice received treatment of normal saline (10 ml/kg), 'caffeine alone' (10mg/kg), 'duloxetine alone' (10mg/kg), 'bupropion alone' (10mg/kg), caffeine+duloxetine (5mg/kg, each), bupropion+caffeine (5mg/kg, each), and bupropion+duloxetine (5mg/kg, each) through the intra-peritoneal route. The immobility period was analyzed 30 min after the treatment in forced swim and tail suspension tests. Norepinephrine, dopamine, and serotonin levels were analyzed in hippocampus, cerebral cortex and whole brain using HPLC with fluorescence detector. Euthanasia was performed 1h after treatment. Comparison between vehicle treated group and other groups showed significant decrease in immobility in all drug treated groups in both antidepressant models. Caffeine plus duloxetine treated group was better among the combination treated groups in terms of decrease in immobility and increase in norepinephrine, dopamine, and serotonin levels in hippocampi, cerebral cortices, and whole brain when compared to their respective monotherapy treated groups. These combination approaches may help in reducing the dose of duloxetine/bupropion, and consequently lower the associated side/adverse effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Antidepressant-like Effect of Kaempferol and Quercitirin, Isolated from Opuntia ficus-indica var. saboten.

    Science.gov (United States)

    Park, Soo-Hyun; Sim, Yun-Beom; Han, Pyung-Lim; Lee, Jin-Koo; Suh, Hong-Won

    2010-06-01

    Opuntia ficus-indica var. saboten. is widely cultivated in Jeju Island (South Korea) for use in manufacture of health foods. This study described antidepressant effect of two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. The expression of the hypothalamic POMC mRNA or plasma β-endorphin levels were increased by extract of Opuntia ficus-indica var. saboten or its flavoniods administered orally. In addition, antidepressant activity was studied using tail suspension test (TST), forced swimming test (FST) and rota-rod test in chronically restraint immobilization stress group in mice. After restraint stress (2 hrs/day for 14 days), animals were kept in cage for 14 days without any further stress, bet with drugs. Mice were fed with a diet supplemented for 14 days and during the behavioral test period with kaempferol or quercitrin (30 mg/kg/day). POMC mRNA or plasma β-endorphin level was increased by extract of Opuntia ficus-indica var. saboten and its flavoniods. In addition, immobility time in TST and FST was significantly reduced by kaempferol or quercitrin. In rota-rod test, the time of permanence was maintained to the semblance of control group in turning at 15 rpm. Our results suggest that two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. show a potent antidepressant effect.

  9. Antidepressant-like Effect of Kaempferol and Quercitirin, Isolated from Opuntia ficus-indica var. saboten

    Science.gov (United States)

    Park, Soo-Hyun; Sim, Yun-Beom; Han, Pyung-Lim; Lee, Jin-Koo

    2010-01-01

    Opuntia ficus-indica var. saboten. is widely cultivated in Jeju Island (South Korea) for use in manufacture of health foods. This study described antidepressant effect of two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. The expression of the hypothalamic POMC mRNA or plasma β-endorphin levels were increased by extract of Opuntia ficus-indica var. saboten or its flavoniods administered orally. In addition, antidepressant activity was studied using tail suspension test (TST), forced swimming test (FST) and rota-rod test in chronically restraint immobilization stress group in mice. After restraint stress (2 hrs/day for 14 days), animals were kept in cage for 14 days without any further stress, bet with drugs. Mice were fed with a diet supplemented for 14 days and during the behavioral test period with kaempferol or quercitrin (30 mg/kg/day). POMC mRNA or plasma β-endorphin level was increased by extract of Opuntia ficus-indica var. saboten and its flavoniods. In addition, immobility time in TST and FST was significantly reduced by kaempferol or quercitrin. In rota-rod test, the time of permanence was maintained to the semblance of control group in turning at 15 rpm. Our results suggest that two flavonoids (kaempferol and quercitrin) isolated from the Opuntia ficus-indica var. saboten. show a potent antidepressant effect. PMID:22110339

  10. Insulin-Like Growth Factor I Produces an Antidepressant-Like Effect and Elicits N-Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Colechio, Elizabeth M; Ghoreishi-Haack, Nayereh; Gross, Amanda; Kroes, Roger A; Stanton, Patric K; Moskal, Joseph R

    2015-09-15

    Growth factors play an important role in regulating neurogenesis and synapse formation and may be involved in regulating the antidepressant response to conventional antidepressants. To date, Insulin-like growth factor I (IGFI) is the only growth factor that has shown antidepressant properties in human clinical trials. However, its mechanism of action remains unclear. The antidepressant-like effect of a single IV dose of IGFI was determined using a chronic unpredictable stress paradigm in the rat Porsolt, sucrose preference, novelty-induced hypophagia, and ultrasonic vocalization models. The dependence of the medial prefrontal cortex for these effects was determined by direct medial prefrontal cortex injection followed by Porsolt testing as well as IGFI receptor activation in the medial prefrontal cortex following an optimal IV antidepressant-like dose of IGFI. The effect of IGFI on synaptic transmission and long-term potentiation (LTP) of synaptic strength was assessed in the hippocampus and medial prefrontal cortex. The dependence of these effects on IGFI and AMPA receptor activation and protein synthesis were also determined. IGFI produced a rapid-acting and long-lasting antidepressant-like effect in each of the depression models. These effects were blocked by IGFI and AMPA receptor antagonists, and medial prefrontal cortex was localized. IGFI robustly increased synaptic strength in the hippocampus and medial prefrontal cortex and these effects were IGFI receptor and protein synthesis-dependent but N-methyl-d-aspartate receptor independent. IGFI also robustly facilitated hippocampal metaplasticity 24 hours postdosing. These data support the conclusion that the antidepressant-like effects of IGFI are mediated by a persistent, LTP-like enhancement of synaptic strength requiring both IGFIR activation and ongoing protein synthesis. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  11. NMDAR inhibition-independent antidepressant actions of ketamine metabolites

    Science.gov (United States)

    Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

    2016-01-01

    Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

  12. A study on evalution of antidepressant effect of imipramine adjunct with Aswagandha and Bramhi.

    Science.gov (United States)

    Maity, T; Adhikari, A; Bhattacharya, K; Biswas, S; Debnath, P K; Maharana, C S

    2011-12-01

    Depressive disorders increase the risks of self-harm or even suicide in patients. Indigenous drugs are being tried to treat such patient along with conventional antidepressant drugs. This study was planned to investigate the antidepressant action of Ashwagandha and Bramhi and also to confirm its efficacy in the behavioural despair animal model of depression. Normal saline as control (5 ml/kg), Imipramine as standard (16, 32, 64 mg/ kg) and Ashwagandha (50, 100, 150 mg/kg), Bramhi (20, 40, 80 mg/kg) as test drugs were introduced to the albino rats weighing between 200-250 gm for 2 weeks, 1 hr before electric shock in Learned helplessness test (LHT) and swimming in Forced swimming test (FST). Effects of individual drugs as well as their combination were evaluated. Avoidance response, escape failure and immobility period in case of Imipramine and Ashwagandha showed highly significant (p < 0.01) result on individual use. There was no significant result in case of Bramhi used alone except in escape failure and immobility period (FST), where at higher doses it showed significant (p < 0.01) result. But combination of Bramhi and Ashwagandha in low doses with low dose of Imipramine gave a highly significant result (p < 0.01) in all the parameters. Ashwagandha had significant antidepressant action, but Bramhi had not when used alone. Combination of these two indigenous drug with Imipramine showed high efficacy in animal model.

  13. Evaluation of anti-inflammatory activity, effect on blood pressure & gastric tolerability of antidepressants

    Directory of Open Access Journals (Sweden)

    Preeta Kaur Chugh

    2013-01-01

    Full Text Available Background & objectives: Antidepressants are being used as analgesics for various pain related disorders like neuropathic and non neuropathic pain. Although their analgesic activity is well recognized but anti-inflammatory potential of antidepressants is still inconclusive. Since the antidepressants are used for longer duration, it becomes important to elucidate effect of anti-depressants on blood pressure and gastric mucosa. This study was undertaken to evaluate the anti-inflammatory potential of various antidepressant drugs as well as their effect on blood pressure and gastric tolerability on chronic administration in rats. Methods: Rat paw oedema model was used for studying anti-inflammatory activity, single dose of test drug (venlafaxine 20 and 40 mg/kg, amitryptline 25 mg/kg, fluoxetine 20 mg/kg was administered intraperitoneally 45 min prior to administration of 0.1 ml of 1 per cent carrageenan in sub-planter region. Oedema induced in test group was compared with normal saline treated control group. For studying effect on blood pressure and gastric tolerability, test drugs were administered for 14 days. Blood pressure was recorded on days 0, 7 and 14 using tail cuff method. On day 14, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. Results: Pretreatment of rats with venlafaxine (40 mg/kg resulted in a significant decrease in paw oedema as compared to control (2.4 ± 0.15 to 1.1 ± 0.16 ml, P<0.01. Similarly, in the group pretreated with fluoxetine, significant decrease in paw oedema was observed in comparison to control (P<0.05. Significant change in mean blood pressure was seen in rats pretreated with venlafaxine 40 mg/kg (126.7 ± 4.2 to 155.2 ± 9.7, P<0.05 and fluoxetine (143.5 ± 2.6 to 158.3 ± 1.2, P<0.05 on day 7. No significant difference with regard to gastric tolerability was observed among groups. Interpretation & conclusions: Our findings showed significant anti

  14. Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis.

    Science.gov (United States)

    Ford, Alexander C; Quigley, Eamonn M M; Lacy, Brian E; Lembo, Anthony J; Saito, Yuri A; Schiller, Lawrence R; Soffer, Edy E; Spiegel, Brennan M R; Moayyedi, Paul

    2014-09-01

    Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence relating to the treatment of this condition with antidepressants and psychological therapies continues to accumulate. We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Trials recruiting adults with IBS, which compared antidepressants with placebo, or psychological therapies with control therapy or "usual management," were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The search strategy identified 3,788 citations. Forty-eight RCTs were eligible for inclusion: thirty-one compared psychological therapies with control therapy or "usual management," sixteen compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Ten of the trials of psychological therapies, and four of the RCTs of antidepressants, had been published since our previous meta-analysis. The RR of IBS symptom not improving with antidepressants vs. placebo was 0.67 (95% CI=0.58-0.77), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms not improving with psychological therapies was 0.68 (95% CI=0.61-0.76). Cognitive behavioral therapy, hypnotherapy, multicomponent psychological therapy, and dynamic psychotherapy were all beneficial. Antidepressants and some psychological therapies are effective treatments for IBS. Despite the considerable number of studies published in the intervening 5 years since we last examined this issue, the overall summary estimates of treatment effect have remained remarkably stable.

  15. Obesity and Its Potential Effects on Antidepressant Treatment Outcomes in Patients with Depressive Disorders: A Literature Review.

    Science.gov (United States)

    Woo, Young Sup; Seo, Hye-Jin; McIntyre, Roger S; Bahk, Won-Myong

    2016-01-12

    Accumulating evidence regarding clinical, neurobiological, genetic, and environmental factors suggests a bidirectional link between obesity and depressive disorders. Although a few studies have investigated the link between obesity/excess body weight and the response to antidepressants in depressive disorders, the effect of weight on treatment response remains poorly understood. In this review, we summarized recent data regarding the relationship between the response to antidepressants and obesity/excess body weight in clinical studies of patients with depressive disorders. Although several studies indicated an association between obesity/excess body weight and poor antidepressant responses, it is difficult to draw definitive conclusions due to the variability of subject composition and methodological differences among studies. Especially, differences in sex, age and menopausal status, depressive symptom subtypes, and antidepressants administered may have caused inconsistencies in the results among studies. The relationship between obesity/excess body weight and antidepressant responses should be investigated further in high-powered studies addressing the differential effects on subject characteristics and treatment. Moreover, future research should focus on the roles of mediating factors, such as inflammatory markers and neurocognitive performance, which may alter the antidepressant treatment outcome in patients with comorbid obesity and depressive disorder.

  16. Synergistic antidepressant-like effect of ferulic acid in combination with piperine: involvement of monoaminergic system.

    Science.gov (United States)

    Li, Gaowen; Ruan, Lina; Chen, Ruijie; Wang, Renye; Xie, Xupei; Zhang, Meixi; Chen, Lichao; Yan, Qizhi; Reed, Miranda; Chen, Jiechun; Xu, Ying; Pan, Jianchun; Huang, Wu

    2015-12-01

    The lifetime prevalence rate for major depressive disorder (MDD) is approximately 17 % for most developed countries around the world. Dietary polyphenols are currently used as an adjuvant therapy to accelerate the therapeutic efficacy on depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is found to have antidepressant-like effects through regulating serotonergic and noradrenergic function. The present study examined the synergistic effect of low doses of FA combined with subthreshold dose of piperine, a bioavailability enhancer, on depression-like behaviors in mice, and investigated the possible mechanism. The administration of FA, even in the highest dose tested, reduced immobility time by 60 % in the tail suspension and forced swimming tests (TST and FST) in mice when compared to control. The maximal antidepressant-like effect of FA was obtained with 200 mg/kg. In addition, piperine only produced a weak antidepressant-like effect in the TST and FST. However, the evidence from the interaction analysis suggested a synergistic effect when low doses of FA were combined with a subthreshold dose of piperine. Further neurochemical evidence such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and measurements of monoamine oxidase activity also supported a synergistic effect of FA and piperine in the enhancement of monoaminergic function. This finding supports the concept that the combination strategy might be an alternative therapy in the treatment of psychiatric disorders with high efficacy and low side effects.

  17. Monoamine reuptake site occupancy of sibutramine: Relationship to antidepressant-like and thermogenic effects in rats.

    Science.gov (United States)

    Li, Yu-Wen; Langdon, Shaun; Pieschl, Rick; Strong, Todd; Wright, Robert N; Rohrbach, Kenneth; Lelas, Snjezana; Lodge, Nicholas J

    2014-08-15

    Sibutramine was formerly marketed as an anti-obesity agent. The current study investigated the relationships between monoamine reuptake site occupancy for sibutramine and both its antidepressant-like efficacy and thermogenic effects. Sibutramine's effects on locomotor activity (LMA) and food intake were also evaluated. Sibutramine occupied monoamine reuptake binding sites with the rank order of potency of NET>SERT>DAT; at 10mg/kg, po, occupancy was 95% NET, 81% SERT and 73% DAT. Sibutramine produced antidepressant-like behavior in the forced swim test; at the lowest effective dose (3mg/kg, po) occupancy was 61%, 90% and 23% at SERT, NET and DAT sites, respectively. Sibutramine also increased body core temperature in a dose- and time-dependent manner; at the lowest effective dose (30mg/kg) SERT, NET and DAT occupancies were respectively 78%, 86% and 59%. A significant decrease in food consumption was observed at 3 and 10mg/kg, po. LMA was increased at ≥10mg/kg, sc. The relationship between efficacy in the FST and occupancy was also determined for citalopram, fluoxetine and reboxetine. Similarly, the relationship between thermogenesis and target occupancy for several single or double/triple reuptake inhibitors was measured and showed that >40-50% DAT binding was required for thermogenesis. Thermogenesis was blocked by the D1 antagonist SCH39166 (3mg/kg, sc). Our findings indicate that the antidepressant-like effect of sibutramine may result from additive or synergistic actions on the three reuptake binding targets. At higher doses, sibutramine produces thermogenesis; DAT inhibition and activation of dopamine D1 receptors are required for this effect. Published by Elsevier B.V.

  18. Antidepressant-like effect of Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L

    OpenAIRE

    El-Alfy, Abir T.; Ivey, Kelly; Robinson, Keisha; Ahmed, Safwat; Radwan, Mohamed; Slade, Desmond; Khan, Ikhlas; ElSohly, Mahmoud; Ross, Samir

    2010-01-01

    The antidepressant action of cannabis as well as the interaction between antidepressants and the endocannabinoid system has been reported. This study was conducted to assess the antidepressant-like activity of Δ9-THC and other cannabinoids. Cannabinoids were initially evaluated in the mouse tetrad assay to determine doses that do not induce hypothermia or catalepsy. The automated mouse forced swim (FST) and tail suspension (TST) tests were used to determine antidepressant action. At doses lac...

  19. State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect.

    Science.gov (United States)

    Yang, Chuan-Chih; Barrós-Loscertales, Alfonso; Pinazo, Daniel; Ventura-Campos, Noelia; Borchardt, Viola; Bustamante, Juan-Carlos; Rodríguez-Pujadas, Aina; Fuentes-Claramonte, Paola; Balaguer, Raúl; Ávila, César; Walter, Martin

    2016-01-01

    The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.

  20. State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect

    Science.gov (United States)

    Yang, Chuan-Chih; Barrós-Loscertales, Alfonso; Pinazo, Daniel; Ventura-Campos, Noelia; Borchardt, Viola; Bustamante, Juan-Carlos; Rodríguez-Pujadas, Aina; Fuentes-Claramonte, Paola; Balaguer, Raúl; Ávila, César; Walter, Martin

    2016-01-01

    The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression. PMID:26998365

  1. State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect

    Directory of Open Access Journals (Sweden)

    Chuan-Chih Yang

    2016-01-01

    Full Text Available The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation and between time points (before versus after training were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.

  2. Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test.

    Science.gov (United States)

    Rénéric, J P; Lucki, I

    1998-03-01

    Because of clinical interest in the effects of antidepressant drugs that exert their effects on multiple neurotransmitter systems, the behavioral effects produced by combined treatment with an SSRI (fluoxetine) with a selective norepinephrine (NE; desipramine) or dopamine (DA) reuptake inhibitor (buproprion) were examined in the forced swimming test (FST), a behavioral test in rodents that predicts the clinical activity of antidepressants. Three additional compounds with mixed activity as NE-5-HT reuptake inhibitors, milnacipran, duloxetine and venlafaxine, were also examined. Desipramine and fluoxetine both reduced immobility in the FST, but desipramine increased only climbing behavior, whereas fluoxetine increased only swimming behavior. The combination of fluoxetine with desipramine or bupropion increased both climbing and swimming behaviors at certain doses, but higher doses of desipramine when combined with fluoxetine replaced swimming behavior with climbing behavior. The mixed NE-5-HT reuptake inhibitors milnacipran and duloxetine reduced immobility and increased climbing behavior, but did not alter swimming. Venlafaxine reduced immobility and increased swimming behavior, except at the highest dose tested (80 mg/kg), which increased both swimming and climbing behaviors. Thus, combining certain doses of pharmacologically selective monoamine reuptake inhibitors, or the mixed reuptake inhibitor venlafaxine, produced a pattern of mixed active behaviors in the FST (climbing and swimming) that may reflect the activity of multiple neurotransmitters, especially the combination of enhanced 5-HT and DA activity. The combination of higher doses of desipramine with fluoxetine, or compounds with mixed activity at inhibiting NE and 5-HT reuptake, demonstrated effects similar to those of desipramine alone and may reflect inhibition of the expression of serotonergic antidepressant behavioral effects by selective NE reuptake inhibitors.

  3. Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical Utility of Targeting Inflammation

    Directory of Open Access Journals (Sweden)

    Manish K. Jha

    2018-01-01

    Full Text Available Major depressive disorder (MDD is a chronic condition that affects one in six adults in the US during their lifetime. The current practice of antidepressant medication prescription is a trial-and-error process. Additionally, over a third of patients with MDD fail to respond to two or more antidepressant treatments. There are no valid clinical markers to personalize currently available antidepressant medications, all of which have similar mechanisms targeting monoamine neurotransmission. The goal of this review is to summarize the recent findings of immune dysfunction in patients with MDD, the utility of inflammatory markers to personalize treatment selection, and the potential of targeting inflammation to develop novel antidepressant treatments. To personalize antidepressant prescription, a c-reactive protein (CRP-matched treatment assignment can be rapidly implemented in clinical practice with point-of-care fingerstick tests. With this approach, 4.5 patients need to be treated for 1 additional remission as compared to a CRP-mismatched treatment assignment. Anti-cytokine treatments may be effective as novel antidepressants. Monoclonal antibodies against proinflammatory cytokines, such as interleukin 6, interleukin 17, and tumor necrosis factor α, have demonstrated antidepressant effects in patients with chronic inflammatory conditions who report significant depressive symptoms. Additional novel antidepressant strategies targeting inflammation include pharmaceutical agents that block the effect of systemic inflammation on the central nervous system. In conclusion, inflammatory markers offer the potential not only to personalize antidepressant prescription but also to guide the development of novel mechanistically-guided antidepressant treatments.

  4. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

    Science.gov (United States)

    Sanches, Rafael Faria; de Lima Osório, Flávia; Dos Santos, Rafael G; Macedo, Ligia R H; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; de Araujo, Draulio Barros; Riba, Jordi; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-02-01

    Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.

  5. Antidepressant-like effects of an alkaloid extract of the aerial parts of Annona cherimolia in mice.

    Science.gov (United States)

    Martínez-Vázquez, M; Estrada-Reyes, R; Araujo Escalona, A G; Ledesma Velázquez, I; Martínez-Mota, L; Moreno, J; Heinze, G

    2012-01-06

    Several species of Annona (Annonaceae) are used in traditional Mexican medicine by their anti-anxiety, anticonvulsant and tranquilizing properties. It has been reported that the alkaloids isolated from some species of the Annona have affinity to serotonergic 5-HT(1A) receptors and modulate dopaminergic transmission, which is involved in depressive disorders. To investigate the antidepressant-like effect of an alkaloid extract from the aerial parts of Annona cherimola (TA) in mice. The antidepressant-like effect was evaluated in the forced swimming test. To elucidate a possible mechanism of action, experiments of synergism with antidepressant drugs, such as imipramine (IMI), clomipramine (CLIMI), and fluoxetine (FLX), were carried out. The neurotransmitter content (DA: dopamine, 5HT: serotonin and its metabolites, HVA: homovanillic acid and 5HIAA: 5-hydroxyindoleacetic) in the whole brain of mice were also determined by HPLC method. TA chemical composition was determined using high performance liquid chromatography-electrospray mass spectrometry. The results showed that repeated treatment with TA produced antidepressant-like effects in mice. This effect was not related to an increase in locomotor activity. Administration of TA facilitated the antidepressant effect of IMI and CLIMI as well as increased the turnover of DA and 5-HT. The alkaloids: 1,2-dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzoquinoline-3,8,9,10-tetraol, anonaine, liriodenine, and nornuciferine were the main constituents of TA. Results showed that TA produces an antidepressant-like action from a generalized increase in monominergic turnover, supporting the use in tradicional medicine of Annona cherimolia, and strongly suggest its therapeutic potency as an antidepressant agent. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF.

    Science.gov (United States)

    Hurley, Laura L; Akinfiresoye, Luli; Nwulia, Evaristus; Kamiya, Atsushi; Kulkarni, Amol A; Tizabi, Yousef

    2013-02-15

    Curcumin is the principal active ingredient found in turmeric (Curcuma longa), a plant used in traditional Asian diets and herbal medicines. It is known to have a wide range of biological actions including antidepressant-like effects which have been observed in stress-induced depression models. This study was designed to investigate the antidepressant potential of curcumin in a non-induced model of depression. Moreover, since brain derived neurotrophic factor (BDNF) has been implicated in antidepressant effects of many drugs, we also evaluated the effects of curcumin on BDNF in the hippocampus. Adult male Wistar Kyoto (WKY) rats, a putative model of depression, were injected acutely or chronically (10d) with 50, 100, and 200mg/kg curcumin. Open field locomotor activity (OFLA) and forced swim test (FST), a measure of helplessness, were measured 1h after acute and 18-20h after last chronic injection. Results showed a dose-dependent reduction of immobility in the FST by curcumin in both acute and chronic studies, without any significant effect on OFLA. The effect of higher chronic curcumin dose in FST was still evident a week later. Chronic curcumin also resulted in a dose-dependent increase in hippocampal BDNF. This data provides evidence for an antidepressant-like effect of curcumin, possibly through increased neurotrophic activity, in the WKY model of depression, and support the notion that curcumin may prove an effective and lasting natural antidepressant. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Antidepressant and skeletal muscle relaxant effects of the aqueous extract of the Prosopis cineraria

    Directory of Open Access Journals (Sweden)

    Mathew George

    2012-09-01

    Full Text Available The aqueous leaves extract of Prosopis cineraria (AEPC is used traditionally for the treatment of various CNS disorder. The purpose of this study was to evaluate the extract for antidepressant and skeletal muscle relaxant activity. The antidepressant effect of the extract was evaluated using Forced swim test (FST. The immobility periods of control and treated mice were recorded. The antidepressant-like effect of tested compound was compared to that of imipramine (15 mg/kg. p.o. Muscle relaxant property was studied using rotarod apparatus and total fall off time for standard and control group was recorded. Phytochemical screening revealed the presence of saponins, flavonoids, alkaloids, glycosides, tannins and phenolic compounds. The leaf extract at doses of 200 mg/kg significantly decreased the duration of immobility time in FST. The efficacy of tested extract was found to be comparable to that of imipramine. Our results suggested that the aqueous extract of Prosopis cineraria leaves exerts antidepressant-like effect.O extrato aquoso de folhas de Prosopis cineraria (AEPC é utilizado, tradicionalmente, para o tratamento de várias disfunções do SNC. O propósito desse estudo foi avaliar o extrato quanto às atividades antidepressiva e relaxante muscular esquelética. O efeito antidepressivo do extrato foi avaliado usando o teste do nado forçado (FST. Registraram-se os períodos de imobilidade dos camundongos controle e dos tratados. O efeito antidepressivo do composto testado foi comparado com a imipramina ((15 mg/kg. p.o. A propriedade relaxante muscular foi estudada usando o cilindro giratório e o tempo total de queda para os grupos padrão e controle foram registrados. A triagem fitoquímica revelou a presença de saponinas, flavonoides, alcaloides, glicosídeos, taninos e compostos fenólicos. O extrato da folha em doses de 200 mg/kg diminui significativamente a duração do tempo de imobilidade no FST. A eficácia do extrato testado foi

  8. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

    Directory of Open Access Journals (Sweden)

    Flávia de L. Osório

    2015-03-01

    Full Text Available Objectives: Ayahuasca (AYA, a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D, the Montgomery-Åsberg Depression Rating Scale (MADRS, and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS. AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

  9. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report.

    Science.gov (United States)

    Osório, Flávia de L; Sanches, Rafael F; Macedo, Ligia R; Santos, Rafael G dos; Maia-de-Oliveira, João P; Wichert-Ana, Lauro; Araujo, Draulio B de; Riba, Jordi; Crippa, José A; Hallak, Jaime E

    2015-01-01

    Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Open-label trial conducted in an inpatient psychiatric unit. Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

  10. Antidepressant mechanism of ketamine: perspective from preclinical studies

    Directory of Open Access Journals (Sweden)

    Lisa eScheuing

    2015-07-01

    Full Text Available A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine’s rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, psychomimetic effects, and increased oxidative stress in the brain, thus limiting its widespread clinical use. To develop superior antidepressant drugs, it is crucial to better understand ketamine’s antidepressant mechanism of action. Recent preclinical studies indicate that ketamine’s antidepressant mechanism involves mammalian target of rapamycin pathway activation and subsequent synaptogenesis in the prefrontal cortex, as well as glycogen synthase kinase-3 beta (GSK-3B inactivation. Adjunct GSK-3B inhibitors, such as lithium, can enhance ketamine’s efficacy by augmenting and prolonging its antidepressant effects. Given the potential for depressive relapses, lithium in addition to ketamine is a promising solution for this clinical issue.

  11. Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

    Directory of Open Access Journals (Sweden)

    Bahareh Amin

    2015-08-01

    Full Text Available Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p. were evaluated using forced swim test (FST. In sub-acute study (21 times with 24-h intervals, antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST. Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Results: Acute treatment with crocin (40 mg/kg and crocetin (20 and 40 mg/kg produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg. Crocetin (12.5, 25 and 50 mg/kg was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Conclusion: Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration.

  12. Abuse and misuse of antidepressants

    Directory of Open Access Journals (Sweden)

    Evans EA

    2014-08-01

    Full Text Available Elizabeth A Evans, Maria A Sullivan Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA Background: Rates of prescription drug abuse have reached epidemic proportions. Large-scale epidemiologic surveys of this under-recognized clinical problem have not included antidepressants despite their contribution to morbidity and mortality. The purpose of this review is to look specifically at the misuse of antidepressants and how this behavior may fit into the growing crisis of nonmedical use of prescription drugs. Methods: We conducted a comprehensive search on PubMed, Medline, and PsycINFO using the search terms “antidepressant”, “abuse”, “misuse”, “nonmedical use”, “dependence”, and “addiction”, as well as individual antidepressant classes (eg, “SSRI” and individual antidepressants (eg, “fluoxetine” in various combinations, to identify articles of antidepressant misuse and abuse. Results: A small but growing literature on the misuse and abuse of antidepressants consists largely of case reports. Most cases of antidepressant abuse have occurred in individuals with comorbid substance use and mood disorders. The most commonly reported motivation for abuse is to achieve a psychostimulant-like effect. Antidepressants are abused at high doses and via a variety of routes of administration (eg, intranasal, intravenous. Negative consequences vary based upon antidepressant class and pharmacology, but these have included seizures, confusion, and psychotic-like symptoms. Conclusion: The majority of individuals prescribed antidepressants do not misuse the medication. However, certain classes of antidepressants do carry abuse potential. Vulnerable patient populations include those with a history of substance abuse and those in controlled environments. Warning signs include the presence of aberrant behaviors. Physicians should include antidepressants when screening for risky prescription

  13. Antidepressant-like Effects of Electroconvulsive Seizures Require Adult Neurogenesis in a Neuroendocrine Model of Depression.

    Science.gov (United States)

    Schloesser, Robert J; Orvoen, Sophie; Jimenez, Dennisse V; Hardy, Nicholas F; Maynard, Kristen R; Sukumar, Mahima; Manji, Husseini K; Gardier, Alain M; David, Denis J; Martinowich, Keri

    2015-01-01

    Neurogenesis continues throughout life in the hippocampal dentate gyrus. Chronic treatment with monoaminergic antidepressant drugs stimulates hippocampal neurogenesis, and new neurons are required for some antidepressant-like behaviors. Electroconvulsive seizures (ECS), a laboratory model of electroconvulsive therapy (ECT), robustly stimulate hippocampal neurogenesis. ECS requires newborn neurons to improve behavioral deficits in a mouse neuroendocrine model of depression. We utilized immunohistochemistry for doublecortin (DCX), a marker of migrating neuroblasts, to assess the impact of Sham or ECS treatments (1 treatment per day, 7 treatments over 15 days) on hippocampal neurogenesis in animals receiving 6 weeks of either vehicle or chronic corticosterone (CORT) treatment in the drinking water. We conducted tests of anxiety- and depressive-like behavior to investigate the ability of ECS to reverse CORT-induced behavioral deficits. We also determined whether adult neurons are required for the effects of ECS. For these studies we utilized a pharmacogenetic model (hGFAPtk) to conditionally ablate adult born neurons. We then evaluated behavioral indices of depression after Sham or ECS treatments in CORT-treated wild-type animals and CORT-treated animals lacking neurogenesis. ECS is able to rescue CORT-induced behavioral deficits in indices of anxiety- and depressive-like behavior. ECS increases both the number and dendritic complexity of adult-born migrating neuroblasts. The ability of ECS to promote antidepressant-like behavior is blocked in mice lacking adult neurogenesis. ECS ameliorates a number of anxiety- and depressive-like behaviors caused by chronic exposure to CORT. ECS requires intact hippocampal neurogenesis for its efficacy in these behavioral indices. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. [Comparison of two assessment tools of antidepressant side-effects: UKU scale versus spontaneous notification].

    Science.gov (United States)

    Gruwez, B; Gury, C; Poirier, M-F; Bouvet, O; Gérard, A; Bourdel, M-C; Baylé, F-J; Olié, J-P

    2004-01-01

    Overall, the efficacy of the newer antidepressants: serotonin selective reuptake inhibitors (SSRI), selective serotonin/norepinephrine reuptake inhibitor (SNRI), noradrenergic and specific serotonergic antidepressant (NaSSA) and tianeptine is similar to that of the tricyclics, and so their acceptability/safety becomes a selection criterion for the clinician. However, side-effect assessment comes up against several difficulties: distinguishing between somatic symptoms caused by the depression and those caused by the treatment -- which assessment tool to use (spontaneous notification, standardized scales that are not specific for the side effects caused by psychotropic drugs, standardised scales specific for the side effects caused by psychotropic drugs, meta-analysis, etc.) -- which data sources to consult (anecdotal reports, reviews, prospective studies), and which data set to use, etc. As a result, the question of the exhaustiveness and reliability of the data consulted by the clinician can arise. We therefore conducted a comparative study in patients treated with these newer antidepressants, of 2 antidepressants side-effect assessment tools: spontaneous notification (SN) versus the UKU scale, a standardised scale specific for the side effects of psychotropic drugs. The depressed outpatients were selected from a psychiatric unit in a French psychiatric hospital and from a non-hospital consulting room. The main inclusion criteria were: male or female subjects, suffering from major depression without melancholia or psychotic features or suffering from mood disorders (according to DSM IV criteria), who had been treated for at least 4 weeks with one of the newer antidepressants. The main exclusion criteria were: any other psychiatric disorder, a serious physical disorder, treatment with neuroleptics, mood-changing drugs or other antidepressants, and patients who were not able to understand the questionnaire. The investigation was carried out by a clinical pharmacist

  15. The Cognitive Effects of Antidepressants in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

    Science.gov (United States)

    Rosenblat, Joshua D; Kakar, Ron; McIntyre, Roger S

    2015-07-25

    Cognitive dysfunction is often present in major depressive disorder (MDD). Several clinical trials have noted a pro-cognitive effect of antidepressants in MDD. The objective of the current systematic review and meta-analysis was to assess the pooled efficacy of antidepressants on various domains of cognition in MDD. Trials published prior to April 15, 2015, were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data from randomized clinical trials assessing the cognitive effects of antidepressants were pooled to determine standard mean differences (SMD) using a random-effects model. Nine placebo-controlled randomized trials (2 550 participants) evaluating the cognitive effects of vortioxetine (n = 728), duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n = 28), nortryptiline (n = 32), and sertraline (n = 49) were identified. Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95% confidence interval [CI] 0.05-0.27; I(2) = 46%) and delayed recall (SMD 0.24; 95% CI 0.15-0.34; I(2) = 0%). The effect on cognitive control and executive function did not reach statistical significance. Of note, after removal of vortioxetine from the analysis, statistical significance was lost for psychomotor speed. Eight head-to-head randomized trials comparing the effects of selective serotonin reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138), and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were identified. No statistically significant difference in cognitive effects was found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and NDRIs. Significant limitations were the heterogeneity of results, limited number of studies, and small sample sizes. Available evidence suggests that antidepressants

  16. Third-person effects and direct-to-consumer advertisements for antidepressants.

    Science.gov (United States)

    Taylor, Laramie D; Bell, Robert A; Kravitz, Richard L

    2011-02-01

    This study examines the evidence for a third- person effect (TPE) in the reactions of individuals affected by depression to direct-to-consumer (DTC) advertisements for antidepressants. TPE predicts that people will perceive the self to be less vulnerable to such advertisements than others. Previous research has identified such an effect, but did so in general population surveys. Past Previous research has also found a link between depression and diminished self-serving biases; whether this would be the case for TPE is unknown. An online questionnaire was administered to 148 participants in an Internet depression support group to investigate their perceptions of the influence of direct-to-consumer (DTC) advertisements for antidepressants. Consistent with expectations derived from third-person effect TPE research, participants, although relatively neutral in their attitudes toward such advertisements, nevertheless perceived other individuals with depression as more influenced than themselves. Positive attitudes towards DTC advertisements and depressive symptoms at the time of the survey were each negatively associated with this third-person perception (TPE). Individuals who have been diagnosed with depression and who participated in an online depression support group believe that they are less vulnerable to the influence of DTC advertisements than the typical person with a history of depression. This is moderated by attitudes towards DTC advertisements as well as by depressive symptoms, each of which is associated with a weakened TPE. © 2010 Wiley-Liss, Inc.

  17. Rosmarinus officinalis polyphenols produce anti-depressant like effect through monoaminergic and cholinergic functions modulation.

    Science.gov (United States)

    Sasaki, Kazunori; El Omri, Abdelfatteh; Kondo, Shinji; Han, Junkyu; Isoda, Hiroko

    2013-02-01

    Rosmarinus officinalis (R. officinalis), a culinary aromatic and medicinal plant, is very rich in polyphenols and flavonoids with high antioxidant properties. This plant was reported to exert multiple benefits for neuronal system and alleviate mood disorder. In our previous study, we demonstrated that R. officinalis and its active compounds, luteolin (Lut), carnosic acid (CA), and rosmarinic acid (RA), exhibited neurotrophic effects and improved cholinergic functions in PC12 cells in correlation with mitogen-activated protein kinase (MAPK), ERK1/2 signaling pathway. The current study was conducted to evaluate and understand the anti-depressant effect of R. officinalis using tail suspension test (TST) in ICR mice and PC12 cells as in vitro neuronal model. Proteomics analysis of PC12 cells treated with R. officinalis polyphenols (ROP) Lut, CA, and RA revealed a significant upregulation of tyrosine hydroxylase (TH) and pyruvate carboxylase (PC) two major genes involved in dopaminergic, serotonergic and GABAergic pathway regulations. Moreover, ROP were demonstrated to protect neuronal cells against corticosterone-induced toxicity. These results were concordant with decreasing immobility time in TST and regulation of several neurotransmitters (dopamine, norepinephrine, serotonin and acetylcholine) and gene expression in mice brain like TH, PC and MAPK phosphatase (MKP-1). To the best of our knowledge this is the first evidence to contribute to the understanding of molecular mechanism behind the anti-depressant effect of R. officinalis and its major active compounds. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Chronic antidepressant and clonidine treatment effects on conflict behavior in the rat.

    Science.gov (United States)

    Commissaris, R L; Ellis, D M; Hill, T J; Schefke, D M; Becker, C A; Fontana, D J

    1990-09-01

    The present studies examined the effects of chronic treatment with several antidepressants and clonidine on conflict behavior. In daily ten-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.25 or 0.5 mA). Electrification was signalled by a tone. Chronic desipramine (5 mg/kg, IP, b.i.d.) or clonidine (40 micrograms/kg, b.i.d.) treatment resulted in time-dependent anticonflict effects, with a latency to onset of approximately 3-4 weeks. In contrast, chronic buproprion (up to 10 mg/kg, IP, b.i.d.), mianserin (up to 10 mg/kg, IP, b.i.d.) or trazodone (up to 40 mg/kg, IP, b.i.d.) treatment resulted in at best only a weak anticonflict effect. The efficacy of these antidepressants and clonidine to increase punished responding when administered chronically correlates well with their efficacy as antipanic agents in man.

  19. Antidepressant and anxiolytic effects of Garcinia indica fruit rind via monoaminergic pathway.

    Science.gov (United States)

    Dhamija, Isha; Parle, Milind; Kumar, Sandeep

    2017-06-01

    Depression and anxiety are the most crippling neuropsychiatric disorders of this modern era. These mostly occur as anxiety followed by depression or in mixed state. Therefore, there is an urgent need of a safe and effective treatment, which proves its worth in this ailment. What else than a conventional food would be a better choice for a convenient therapy. Therefore, Garcinia indica, commonly known as Kokam, fruit rind has been used in the present study to investigate its antidepressant and anti-anxiety potential using forced swim test, tail suspension test, and reserpine-induced hypothermia; and elevated plus maze, hole-board test, and light dark model, respectively. Garcinia indica fruit rind given to mice with food for consecutive 14 days at 0.5, 1, and 2% w/w significantly (p indica significantly (p indica significantly reduced monoamine oxidase and malondialdehyde levels providing support to neuroprotective potential of fruit rind. The mechanistic study showed the participation of G. indica at α1-adrenoceptor and D2-dopamine receptor, by attenuating prazosin and sulpiride-induced increase in immobility duration. Garcinia indica fruit rind showed a significant antidepressant and anxiolytic effect while no effect on locomotor activity, i.e., no psycho-stimulation.

  20. Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice.

    Science.gov (United States)

    Vogt, M A; Mallien, A S; Pfeiffer, N; Inta, I; Gass, P; Inta, D

    2016-03-15

    Minocycline is a broad-spectrum tetracycline antibiotic with multiple actions, including anti-inflammatory and neuroprotective effects, that was proposed as novel treatment for several psychiatric disorders including schizophrenia and depression. However, there are contradictory results regarding antidepressant effects of minocycline in rodent models. Additionally, the possible anxiolytic effect of minocycline is still poorly investigated. Therefore, we aimed to clarify in the present study the influence of minocycline on behavioral correlates of mood disorders in standard tests for depression and anxiety, the Porsolt Forced Swim Test (FST), Elevated O-Maze, Dark-Light Box Test and Openfield Test in adult C57BL/6 mice. We found, unexpectedly, that mice treated with minocycline (20-40mg/kg, i.p.) did not display antidepressant- or anxiolytic-like behavioral changes in contrast to mice treated with diazepam (0.5mg/kg, anxiety tests) or imipramine (20mg/kg, depressive-like behavior). These results are relevant for future studies, considering that C57BL/6 mice, the most widely used strain in pharmacological and genetic animal models, did not react as expected to the treatment regime applied. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression.

    Science.gov (United States)

    Peciña, Marta; Bohnert, Amy S B; Sikora, Magdalena; Avery, Erich T; Langenecker, Scott A; Mickey, Brian J; Zubieta, Jon-Kar

    2015-11-01

    High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. To examine neurochemical mechanisms underlying the formation of placebo effects in patients with major depressive disorder (MDD). In this study involving 2 placebo lead-in phases followed by an open antidepressant administration, we performed a single-blinded 2-week crossover randomized clinical trial of 2 identical oral placebos (described as having either active or inactive fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor or, in some cases, another agent as clinically indicated. The volunteers (35 medication-free patients with MDD at a university health system) were studied with positron emission tomography and the µ-opioid receptor-selective radiotracer [11C]carfentanil after each 1-week inactive and active oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously within sight of the volunteer during positron emission tomographic scanning every 4 minutes over 20 minutes only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was used to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. Changes in depressive symptoms in response to active placebo and antidepressant. Baseline and activation measures of µ-opioid receptor binding. Higher baseline µ-opioid receptor binding in the nucleus accumbens was associated with better response to antidepressant treatment (r = 0.48; P = .02). Reductions in depressive symptoms after 1 week of active placebo treatment, compared with the inactive, were associated with increased placebo-induced µ-opioid neurotransmission in a network of regions implicated in emotion, stress

  2. Antidepressant Withdrawal

    Science.gov (United States)

    ... symptoms than others. Quitting an antidepressant suddenly may cause symptoms within a day or two, such as: Anxiety Insomnia or vivid dreams Headaches Dizziness Tiredness Irritability Flu-like symptoms, including ...

  3. [Modern antidepressants and hallucinations].

    Science.gov (United States)

    Kolthof, H J

    2014-01-01

    A case-vignette illustrates that hallucinations can be an unusual, but potentially serious side-effect of modern antidepressants. To examine the frequency with which these hallucinations occur and to describe adequate clinical treatment. Information was obtained by searching literature and the database of the Netherlands Pharmacovigilance Centre Lareb. The literature reported only a few case-vignettes about hallucinations associated with treatment with sertraline. The search of the Lareb database revealed that hallucinations can occur in any age-group and with any modern antidepressant. Age, the use of co-medication, inherent neurodegenerative or psychiatric disorders are possible risk factors. When patients develop hallucinations, good clinical practise seems to be withdrawal of the prescribed antidepressant. If necessary, a different antidepressant can be tried.

  4. Evaluation of analgesic, anti-inflammatory, anti-depressant and anti-coagulant properties of Lactuca sativa (CV. Grand Rapids) plant tissues and cell suspension in rats.

    Science.gov (United States)

    Ismail, Hammad; Mirza, Bushra

    2015-06-27

    Lactuca sativa (lettuce) has been traditionally used for relieving pain, inflammation, stomach problems including indigestion and lack of appetite. Moreover, the therapeutic significance of L. sativa includes its anticonvulsant, sedative-hypnotic and antioxidant properties. In the present study, the MC (methanol and chloroform; 1:1) and aqueous extracts of seed and leaf along with cell suspension exudate were prepared. These extracts were explored for their analgesic, anti-inflammatory, antidepressant and anticoagulant effects by hot plate analgesic assay; carrageenan induced hind paw edema test, forced swimming test and capillary method for blood clotting respectively in a rat model. The results were analyzed using one-way Analysis of Variance (ANOVA) followed by Turkey multiple comparison test. Interestingly, the extracts and the cell suspension exudate showed dual inhibition by reducing pain and inflammation. The results indicated that the aqueous extracts of leaf exhibited highest analgesic and anti-inflammatory activities followed by leaf MC, cell suspension exudate, seed aqueous and seed MC extracts. The current findings show that aqueous and MC extracts of seed have the least immobility time in the forced swimming test, which could act as an anti-depressant on the central nervous system. The leaf extracts and cell suspension exudate also expressed moderate anti-depressant activities. In anticoagulant assay, the coagulation time of aspirin (positive control) and MC extract of leaf was comparable, suggesting strong anti-coagulant effect. Additionally, no abnormal behavior or lethality was observed in any animal tested. Taken together, L. sativa can potentially act as a strong herbal drug due to its multiple pharmaceutical effects and is therefore of interest in drug discovery and development of formulations.

  5. Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

    Science.gov (United States)

    Ma, Xian-Cang; Chu, Zheng; Zhang, Xiao-Ling; Jiang, Wen-Hui; Jia, Min; Dang, Yong-Hui; Gao, Cheng-Ge

    2016-06-01

    The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

  6. Antidepressant effect of recombinant NT4-NAP/AAV on social isolated mice through intranasal route.

    Science.gov (United States)

    Liu, Fei; Liu, You-Ping; Lei, Gang; Liu, Peng; Chu, Zheng; Gao, Cheng-Ge; Dang, Yong-Hui

    2017-02-07

    The purpose of the present study was to observe the depression-like behavior induced by social isolation; detect the antidepressant effect of a recombinant adeno-associated virus (AAV) expressing NAP on social isolation mice by intranasal delivery. After construction of NT4-NAP/AAV, expression of NAP was confirmed in vitro. 3-week-old C57/BL mice were bred individually in cages as social isolation-rearing. Six weeks later, the first subset of mice underwent behavioral tests and western blot; the second was for enzyme-linked immunosorbent assay. NT4-NAP/AAV was delivered quaque die by nasal administration for consecutive 10 days before behavioral test. Several depression-like behaviors were observed in social isolation mice, including decreased relative sucrose preference, longer immobility time in forced swimming test, lower plasma corticosterone and decreased brain-derived neurotrophic factor in hippocampus. Thus, social isolation procedure appears to be an animal model of depression with good face and construct validity. What's more, the antidepressant effect in social isolation-rearing mice was observed after intranasal administration of NT4-NAP/AAV, suggesting that this might be a promising therapeutic strategy for depressive disorder.

  7. Adverse effects of the SSRI antidepressant sertraline on early life stages of marine invertebrates.

    Science.gov (United States)

    Estévez-Calvar, Noelia; Canesi, Laura; Montagna, Michele; Faimali, Marco; Piazza, Veronica; Garaventa, Francesca

    2017-07-01

    Widespread contamination of coastal environments by emerging compounds includes low concentrations of pharmaceuticals. These pollutants are not currently incorporated in monitoring programs despite their effects on non-target organisms are very little documented. Among the selective serotonin reuptake inhibitor (SSRI) antidepressants, sertraline (SRT) is one of the most prescribed globally. In this work, earlier life stages of Amphibalanus amphitrite, Brachionus plicatilis and Mytilus galloprovincialis were exposed to environmental concentrations of SRT in order to study both sub-lethal and lethal responses in 24/48 h-tests. Low concentrations of SRT altered significantly swimming behavior in A. amphitrite and B. plicatilis giving 48 h-EC50 (μg/L) of 113.88 and 282.23, respectively whereas higher values were observed for mortality and immobilization. EC50 embryotoxicity with M. galloprovincialis was 206.80 μg/L. This work add new data about SRT ecotoxicity on marine invertebrates and confirms the applicability of behavioral endpoints to evaluate the environmental impact of antidepressants in marine organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Antidepressant efficacy and side-effect burden: a quick guide for clinicians

    Directory of Open Access Journals (Sweden)

    Daniel Santarsieri

    2015-10-01

    Full Text Available Prescribing of antidepressant treatment (ADT for major depressive disorder (MDD has increased in quantity and popularity over the last two decades. This is likely due to the approval of safer medications, better education of clinicians and their patients, direct-to-consumer marketing practices, and less stigma associated with those taking ADT. This trend has also been met with some controversy, however, as the ongoing safety and effectiveness of these treatments have at times been called into question. This paper discusses the differing levels of evidence that support the use of ADT based on (A Food and Drug Administration approvals, (B data from randomized controlled trials or meta-analyses and, where these are not available, the authors discuss and apply, (C theoretical pharmacodynamic principles to justify antidepressant choice in the treatment of MDD patients. The final section discusses standard psychopharmacology guideline approaches to better alert the reader as to which practices are commonplace compared with those which are more outside of the standard of care.

  9. Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice

    Science.gov (United States)

    Almatroudi, Abdulrahman; Husbands, Stephen M.; Bailey, Christopher P.; Bailey, Sarah J.

    2016-01-01

    Opiates have been used historically for the treatment of depression. Renewed interest in the use of opiates as antidepressants has focussed on the development of kappa opioid receptor (κ-receptor) antagonists. Buprenorphine acts as a partial μ-opioid receptor agonist and a κ-receptor antagonist. By combining buprenorphine with the opioid antagonist naltrexone, the activation of μ-opioid receptors would be reduced and the κ-antagonist properties enhanced. We have established that a combination dose of buprenorphine (1mg/kg) with naltrexone (1mg/kg) functions as a short-acting κ-antagonist in the mouse tail withdrawal test. Furthermore, this dose combination is neither rewarding nor aversive in the conditioned place preference paradigm and is without significant locomotor effects. We have shown for the first time that systemic co-administration of buprenorphine (1mg/kg) with naltrexone (1mg/kg) in CD-1 mice produced significant antidepressant-like responses in behaviours in both the forced swim test and novelty induced hypophagia task. Behaviours in the elevated plus maze and light dark box were not significantly altered by treatment with buprenorphine alone, or in combination with naltrexone. We propose that the combination of buprenorphine with naltrexone represents a novel, and potentially a readily translatable approach, to the treatment of depression. PMID:26045511

  10. [Cellular and molecular effects of the antidepressant hyperforin on brain cells: Review of the literature].

    Science.gov (United States)

    Bouron, A; Lorrain, E

    2014-04-01

    Hypericum perforatum is, with Ginkgo biloba, one of the most frequently prescribed medicinal plants in the world. Its popular name, St. John's wort (SJW), is due to the fact that its flowers, yellow, are gathered around the feast of St. John the Baptist (24th June) whereas "wort" is an old English word for plant. Of interest, SJW possesses antidepressant actions and is currently used to alleviate symptoms of mild to moderate depression. Nearly two dozens of bioactive compounds have been isolated from SJW. Hypericin, originally described as a monoamine oxidase inhibitor type A, was thought to be responsible for the antidepressant properties of SJW extracts. However, subsequent studies could not confirm this observation and hyperforin, a phloroglucinol derivative, was shown to display antidepressive properties. Indeed, the efficiency of the extracts of SJW has been reported to be dependent on the concentration of hyperforin. However, its effects on brain cells and on the mechanisms underlying its putative clinical antidepressant effect remain poorly characterized. The aim of this review article is to propose an overview of the recent scientific publications that have provided new and relevant insights into the neurobiological actions of hyperforin. Hyperforin has been described as an inhibitor of the reuptake of many neurotransmitters such as dopamine, norepinephrine, serotonin or glutamate. It is thus a potent modulator of synaptic transmission. In addition, it blocks the activity of many receptors such as gamma-aminobutyric acid (GABA) and N-Methyl-D-aspartate (NMDA) receptors. More recently, hyperforin has been shown to activate TRPC6, a Ca(2+)-conducting channel of the plasma membrane, which is the only channel opened by this molecule. Interestingly, the other transient receptor potential channels of C type (TRPC) isoforms (TRPC1, TRPC3, TRPC4, TRPC5 and TRPC7) are insensitive to hyperforin. Due to this specific property, it is now used as a convenient

  11. [Antidepressive agents and memory].

    Science.gov (United States)

    Danion, J M

    1993-07-01

    It is important that antidepressants, now increasingly used in ambulatory treatment of many patients, should not be detrimental to cognition and memory. It is difficult to assess these effects. One must make a distinction between the direct effects of antidepressants on cognition, related to their intrinsic properties, and indirect effects secondary to mood improvement. The tests used in studies essentially focus on psychomotricity and do not accurately evaluate the effects on cognition itself. Indeed, there are different kinds of memory which would require specific investigations. It has nevertheless been demonstrated that acute administration of sedative antidepressants with a marked anticholinergic component are detrimental to the memory processes. However, following prolonged administration, tolerance may develop within 1 to 3 weeks. Some antidepressants, however, especially serotonergics, do not cause any disturbances of memory. In depressed subjects, it seems that, overall, long-term antidepressant treatment improves cognitive functions. This effect is due to the combination of drug tolerance and of the indirect effects secondary to mood improvement. Elderly subjects appear to be more sensitive to the detrimental effects on memory and they develop drug tolerance more slowly. Lastly, two studies have reported that serotonin re-uptake inhibitors might have beneficial effects on memory disorders secondary to acute or chronic alcohol abuse.

  12. Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

    Science.gov (United States)

    Mohamed, Somaia; Johnson, Gary R; Chen, Peijun; Hicks, Paul B; Davis, Lori L; Yoon, Jean; Gleason, Theresa C; Vertrees, Julia E; Weingart, Kimberly; Tal, Ilanit; Scrymgeour, Alexandra; Lawrence, David D; Planeta, Beata; Thase, Michael E; Huang, Grant D; Zisook, Sidney; Rao, Sanjai D; Pilkinton, Patricia D; Wilcox, James A; Iranmanesh, Ali; Sapra, Mamta; Jurjus, George; Michalets, James P; Aslam, Muhammed; Beresford, Thomas; Anderson, Keith D; Fernando, Ronald; Ramaswamy, Sriram; Kasckow, John; Westermeyer, Joseph; Yoon, Gihyun; D'Souza, D Cyril; Larson, Gunnar; Anderson, William G; Klatt, Mary; Fareed, Ayman; Thompson, Shabnam I; Carrera, Carlos J; Williams, Solomon S; Juergens, Timothy M; Albers, Lawrence J; Nasdahl, Clifford S; Villarreal, Gerardo; Winston, Julia L; Nogues, Cristobal A; Connolly, K Ryan; Tapp, Andre; Jones, Kari A; Khatkhate, Gauri; Marri, Sheetal; Suppes, Trisha; LaMotte, Joseph; Hurley, Robin; Mayeda, Aimee R; Niculescu, Alexander B; Fischer, Bernard A; Loreck, David J; Rosenlicht, Nicholas; Lieske, Steven; Finkel, Mitchell S; Little, John T

    2017-07-11

    Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1

  13. NMDA GluN2B receptors involved in the antidepressant effects of curcumin in the forced swim test.

    Science.gov (United States)

    Zhang, Lin; Xu, Tianyuan; Wang, Shuang; Yu, Lanqing; Liu, Dexiang; Zhan, Renzhi; Yu, Shu Yan

    2013-01-10

    The antidepressant-like effect of curcumin, a major active component of Curcuma longa, has been previously demonstrated in the forced swimming test. However, the mechanism of this beneficial effect on immobility scores, which is used to evaluate antidepressants, remains largely uncharacterized. The present study attempts to investigate the effects of curcumin on depressive-like behavior with a focus upon the possible contribution of N-methyl-D-aspartate (NMDA) subtype glutamate receptors in this antidepressant-like effect of curcumin. Male mice were pretreated with specific receptor antagonists to different NMDA receptor subtypes such as CPP, NVP-AAM077 and Ro25-6981 as well as to a partial NMDA receptor agonist, D-cycloserine (DCS), prior to administration of curcumin to observe the effects on depressive behavior as measured by immobility scores in the forced swim test. We found that pre-treatment of mice with CPP, a broad-spectrum competitive NMDA receptor antagonist, blocked the anti-immobility effect of curcumin, suggesting the involvement of the glutamate-NMDA receptors. While pretreatment with NVP-AAM077 (the GluN2A-preferring antagonist) did not affect the anti-immobility effect of curcumin, Ro25-6981 (the GluN2B-preferring antagonist) was found to prevent the effect of curcumin in the forced swimming test. Furthermore, pre-treatment with a sub-effective dose of DCS potentiated the anti-immobility effect of a sub-effective dose of curcumin in the forced swimming test. Taken together, these results suggest that curcumin shows antidepressant-like effects in mice and the activation of GluN2B-containing NMDARs is likely to play a predominate role in this beneficial effect. Therefore, the antidepressant-like effect of curcumin in the forced swim test may be mediated, at least in part, by the glutamatergic system. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Interactive Effects of Prenatal Antidepressant Exposure and Likely Gene Disrupting Mutations on the Severity of Autism Spectrum Disorder

    Science.gov (United States)

    Ackerman, Sean; Schoenbrun, Sarah; Hudac, Caitlin; Bernier, Raphael

    2017-01-01

    To examine the interactive effects of two proposed risk factors which may contribute to symptom severity of Autism Spectrum Disorder (ASD): prenatal antidepressant exposure and likely gene-disrupting (LGD) mutations. Participants included 2748 individuals with ASD from the Simons Simplex Collection. We examined the effects of prenatal…

  15. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

    Directory of Open Access Journals (Sweden)

    Aviva Breuer

    Full Text Available Cannabidiol (CBD is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101 (1, is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.

  16. Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.

    Science.gov (United States)

    Breuer, Aviva; Haj, Christeene G; Fogaça, Manoela V; Gomes, Felipe V; Silva, Nicole Rodrigues; Pedrazzi, João Francisco; Del Bel, Elaine A; Hallak, Jaime C; Crippa, José A; Zuardi, Antonio W; Mechoulam, Raphael; Guimarães, Francisco S

    2016-01-01

    Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.

  17. Effect of educational outreach on general practice prescribing of antibiotics and antidepressants: A two-year randomised controlled trial

    Science.gov (United States)

    Enriquez-puga, Andres; Baker, Richard; Paul, Sanjoy; Villoro-Valdes, Renata

    2009-01-01

    Objective Prescribing of broad spectrum antibiotics and antidepressants in general practice often does not accord with guidelines. The aim was to determine the effectiveness of educational outreach in improving the prescribing of selected antibiotics and antidepressants, and whether the effect is sustained for two years. Design Single blind randomized trial. Setting Twenty-eight general practices in Leicestershire, England. Intervention Educational outreach visits were undertaken, tailored to barriers to change, 14 practices receiving visits for reducing selected antibiotics and 14 for improving antidepressant prescribing. Main outcome measures Number of items prescribed per 1000 registered patients for amoxicillin with clavulanic acid (co-amoxiclav) and quinolone antibiotics, and average daily quantities per 1000 patients for lofepramine and fluoxetine antidepressants, measured at the practice level for six-month periods over two years. Results There was no effect on the prescribing of co-amoxiclav, quinolones, or fluoxetine, but prescribing of lofepramine increased in accordance with the guidelines. The increase persisted throughout two years of follow-up. Conclusion A simple, group-level educational outreach intervention, designed to take account of identified barriers to change, can have a modest but sustained effect on prescribing levels. However, outreach is not always effective. The context in which change in prescribing practice is being sought, the views of prescribers concerning the value of the drug, or other unrecognised barriers to change may influence the effectiveness of outreach. PMID:19958063

  18. Rhythmical Photic Stimulation at Alpha Frequencies Produces Antidepressant-Like Effects in a Mouse Model of Depression.

    Directory of Open Access Journals (Sweden)

    Shinheun Kim

    Full Text Available Current therapies for depression consist primarily of pharmacological agents, including antidepressants, and/or psychiatric counseling, such as psychotherapy. However, light therapy has recently begun to be considered as an effective tool for the treatment of the neuropsychiatric behaviors and symptoms of a variety of brain disorders or diseases, including depression. One methodology employed in light therapy involves flickering photic stimulation within a specific frequency range. The present study investigated whether flickering and flashing photic stimulation with light emitting diodes (LEDs could improve depression-like behaviors in a corticosterone (CORT-induced mouse model of depression. Additionally, the effects of the flickering and flashing lights on depressive behavior were compared with those of fluoxetine. Rhythmical flickering photic stimulation at alpha frequencies from 9-11 Hz clearly improved performance on behavioral tasks assessing anxiety, locomotor activity, social interaction, and despair. In contrast, fluoxetine treatment did not strongly improve behavioral performance during the same period compared with flickering photic stimulation. The present findings demonstrated that LED-derived flickering photic stimulation more rapidly improved behavioral outcomes in a CORT-induced mouse model of depression compared with fluoxetine. Thus, the present study suggests that rhythmical photic stimulation at alpha frequencies may aid in the improvement of the quality of life of patients with depression.

  19. Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?

    Science.gov (United States)

    Postuma, Ronald B; Gagnon, Jean-Francois; Tuineaig, Maria; Bertrand, Josie-Anne; Latreille, Veronique; Desjardins, Catherine; Montplaisir, Jacques Y

    2013-11-01

    Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration. Prospective cohort study. Tertiary sleep disorders center. 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls. Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74). Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.

  20. Identification of the Chemical Constituents in Aqueous Extract of Zhi-Qiao and Evaluation of Its Antidepressant Effect

    Directory of Open Access Journals (Sweden)

    Ming Wu

    2015-04-01

    Full Text Available The immature fruit of Citrus aurantium L. (Zhi-Qiao, ZQ has been used as a traditional medicine in China. Our previous study has shown that ZQ decoction may contribute to the antidepressant-like action of Chaihu-Shu-Gan-San. However, there are no reports on the chemical constituents of ZQ aqueous extract or its anti-depression effects. Firstly, this research reported the on-line identification of the chemical constituents in the aqueous extract of ZQ by coupling ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF/MS. A total of 31 chemical constituents were identified in ZQ aqueous extract, including one tannic acid, five flavones, 13 flavanones, one limonoid, three coumarins, three cyclic peptides, and five polymethoxylated flavonoids. The antidepressant effect of ZQ aqueous extract was evaluated in vivo and the results indicated that the mice immobility time during the forced swimming test and the tail suspension test were significantly reduced with ZQ treatment. MTT assays showed both ZQ aqueous extract and its major constituents (naringin, hesperidin, neohesperidin, and nobiletin had neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells. The in vivo and in vitro results suggest that ZQ has an antidepressant effect.

  1. SREBP activation by antipsychotic- and antidepressant-drugs in cultured human liver cells: relevance for metabolic side-effects?

    Science.gov (United States)

    Raeder, Maria B; Fernø, Johan; Vik-Mo, Audun O; Steen, Vidar M

    2006-09-01

    Drug-induced weight gain is a major problem in the treatment of psychiatric disorders, especially with some antipsychotic- and antidepressant drugs. We have recently demonstrated that antipsychotic- and antidepressant drugs activate the SREBP (sterol regulatory element-binding proteins) transcription factors in human- and rat glial cells, with subsequent up-regulation of downstream genes involved in cholesterol- and fatty acid biosynthesis. Since stimulation of cellular lipogenesis in the liver could be of relevance for the metabolic side effects of these drugs, we have now investigated the effects of antidepressants, antipsychotic- and mood-stabilizing drugs on cell cultures of human liver cells. For several of the drugs being strongly associated with weight gain (clozapine, imipramine, and amitriptyline), we observed a very pronounced activation of SREBP. Ziprasidone and buproprion, however, which are not associated with weight gain, did hardly stimulate the SREBP system. For haloperidol, olanzapine and mirtazapine, the correspondence between metabolic side effects and SREBP stimulation in liver cells was less obvious. The mood-stabilizers did not increase SREBP activation. The results indicate a relationship between drug-induced activation of SREBP in cultured human liver cells and weight gain side-effects of antidepressant and antipsychotic drugs.

  2. Personality test and prediction of antidepressive treatment effect in mental illness

    DEFF Research Database (Denmark)

    Thorleifsson, Ari; Holst, Klaus; Diaz, Marta

    2010-01-01

    in advance those patients in whom adjuvant therapy would be of a special benefit. MATERIAL AND METHODS: Answers to questions about personality traits (Temperament and Character Inventory (TCI)) were gathered from a mixed group of hospitalized and ambulant Danish psychiatric patients (n = 63) and matched...... with answers to questions on quality of life and degree of depression (Major Depression Inventory (MDI)). The hospitalized patients answered those questions again when discharged. Confirmatory factor analysis was used to evaluate the quality of the questions with regard to their information on latent...... ambulant treatment. CONCLUSION: The TCI screening identifies a group of patients that have a high risk of getting a limited antidepressive treatment effect. An adjuvant intervention to the psychopharmacologic treatment could be offered, e.g. cognitive therapy. Udgivelsesdato: 2010...

  3. The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

    Science.gov (United States)

    Kaminska, K; Rogoz, Z

    2016-06-01

    Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

  4. Antidepressant-Like Effects of Cordycepin in a Mice Model of Chronic Unpredictable Mild Stress

    Directory of Open Access Journals (Sweden)

    Zhang Tianzhu

    2014-01-01

    Full Text Available Cordycepin (3′-deoxyadenosine, a major bioactive component isolated from Cordyceps militaris, has multiple pharmacological activities. This study is attempted to investigate whether cordycepin (COR possesses beneficial effects on chronic unpredictable mild stress- (CUMS- induced behavioral deficits (depression-like behaviors and explore the possible mechanisms. ICR mice were subjected to chronic unpredictable mild stress for 42 consecutive days. Then, COR and fluoxetine (FLU, positive control drug were administered for 21 consecutive days at the last three weeks of CUMS procedure. The classical behavioral tests, open field test (OFT, sucrose preference test (SPT, tail suspension test (TST, and forced swimming test (FST, were applied to evaluate the antidepressant effects of COR. Then the serotonin (5-HT and noradrenaline (NE concentrations in hippocampal were evaluated by HPLC; tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 in hippocampal were evaluated, and the proteins of TNF-α, IL-6, NF-κBP65 5-HT receptor (5-HTR, and brain-derived neurotrophic factor (BDNF in hippocampal were evaluated by Western blot. Our results indicated that 6 weeks of CUMS exposure induced significant depression-like behavior, with low 5-HT and NE levels, high TNF-α and IL-6 in brain and high hippocampal TNF-α, IL-6, P-NF-κBP65, and 5-HTR levels, and low BDNF expression levels. Whereas, chronic COR (20, 40 mg/kg treatments reversed the behavioral deficiency induced by CUMS exposure, treatment with COR normalized the change of TNF-α, IL-6, 5-HT, and NE levels, which demonstrated that COR could partially restore CUMS-induced 5-HT receptor impairments and inflammation. Besides, hippocampal BDNF expressions were also upregulated after COR treatments. In conclusion, COR remarkably improved depression-like behavior in CUMS mice and its antidepressant activity is mediated, at least in part, by the upregulating BDNF and downregulating 5-HTR levels and

  5. The Antidepressant Effect of L-Tyrosine-Loaded Nanoparticles: Behavioral Aspects.

    Science.gov (United States)

    Alabsi, Abdelrahman; Khoudary, Adel Charbel; Abdelwahed, Wassim

    2016-07-01

    Depression has been linked to disruption in the cerebral levels of specific neurotransmitters. L-tyrosine is a precursor of more than one of the neurotransmitters affected by depression. Even though setbacks of monoamines precursors include high doses and low efficiency, many studies have suggested using L-tyrosine as antidepressant. The purpose of this study was to explore the possible antidepressant effect of L-tyrosine loaded in a nanoparticle-designed formula, using behavioral tests in acute and chronic mild stress (CMS) models of depression in rats. Animals from both models received L-tyrosine-loaded nanoparticles (5 or 10 mg/kg), L-tyrosine solution (10 mg/kg), fluoxetine (10 mg/kg) or placebo daily for 21 days. Rats from the acute stress model of depression were subjected to open field and forced swim tests (FSTs). For the CMS model, sucrose preference test was carried out. Additionally, 3 profiles of the nanoparticles formula were tested in vitro. High dissolution rate and entrapment efficiency were obtained from the in vitro tests. Moreover, L-tyrosine-loaded nanoparticles 10 mg/kg and fluoxetine 10 mg/kg significantly decreased the immobility time in the FST, concomitant with restoration of the basal levels of locomotor activity, distance travelled and rearing counts. Also, an increase of the sucrose consumption was recorded in the sucrose preference test after treatment with L-tyrosine-loaded nanoparticles 10 mg/kg and fluoxetine 10 mg/kg. The positive results after treatment with L-tyrosine-loaded nanoparticles, through behavioral tests, are probably attributed to restorating the basal levels of the cerebral noradrenaline. The effects of L-tyrosine administration on the cerebral levels of tyrosine hydroxylase and corticotropin-releasing factor should be further investigated.

  6. Anxiolytic- and antidepressant-like effects of an aqueous extract of Tanacetum parthenium L. Schultz-Bip (Asteraceae) in mice.

    Science.gov (United States)

    Cárdenas, Jorge; Reyes-Pérez, Valeria; Hernández-Navarro, María Dolores; Dorantes-Barrón, Ana María; Almazán, Salvador; Estrada-Reyes, Rosa

    2017-03-22

    Tanacetum parthenium L. Schultz-Bip (Asteraceae) is widely used worldwide in traditional medicine for the treatment of convulsions and culture-bound syndromes such as susto (fear). The aim of this work was to evaluate the anxiolytic- and antidepressant-like effects of an aqueous extract of T. parthenium in behavioral paradigms in mice. The effects of T. parthenium were compared with those produced by anxiolytic and antidepressant drugs. We carried out the chemical characterization of the main constituents of T. parthenium. The involvement with the GABAergic and serotoninergic neurotransmitter systems were explored be means of synergic and antagonist experiments. The anxiolytic-like effect was evaluated using the Burying Behavior Test (BBT) and the Elevated Plus-Maze Test (PMT). The antidepressant-like effect was evaluated in the Forced Swimming Test (FST), and ambulatory activity was assessed in the Open Field Test (OFT). Employing the behavioral tests, synergism and antagonism experiments with Alprazolam, Muscimol, and Picrotoxin were carried out in the PMT. In a series of independent experiments, concomitant administration of T. parthenium and Alprazolam, Fluoxetine, or p-chlorophenylalanine were conducted in the FST. For chemical characterization, High-Performance Liquid Chromatography-Electro Spray Ionization-Mass Spectrometry (HPLC-ESI-MS) analysis was performed. T. parthenium exerts clear anxiolytic- and antidepressant-like effects in mice, without affecting the ambulatory activity of the experimental subjects. Anxiolytic- and antidepressant-like T. parthenium effects result, at least part from the involvement of the GABAergic system. Our results support the use of Tanacetum parthenium in traditional medicine and suggest its therapeutic potential in the comorbid anxiety and depression. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Joint effects of nine antidepressants on Raphidocelis subcapitata and Skeletonema marinoi: A matter of amine functional groups.

    Science.gov (United States)

    Minguez, Laetitia; Bureau, Ronan; Halm-Lemeille, Marie-Pierre

    2018-03-01

    Antidepressants are among the most prescribed pharmaceuticals throughout the world. Their presence has already been detected in several aquatic ecosystems worldwide and their effects on non-target organisms justify the growing concern of both the public and regulatory authorities. These emerging pollutants do not occur as isolated compounds but rather as multi-component mixtures, which may lead to increased adverse effects compared to individual compounds. Freshwater and marine algae seem particularly sensitive to pharmaceuticals, including antidepressants. Studies assessing the toxicity of antidepressant mixture to algae focused mainly on binary mixtures of selective serotonin reuptake inhibitors. In the present experiment, the freshwater algae Raphidocelis subcapitata (formerly known as Pseudokirchneriella subcapitata) and the marine diatom Skeletonema marinoi were exposed to equitoxic mixtures of 9 antidepressants (fluvoxamine, fluoxetine, sertraline, duloxetine, venlafaxine, clomipramine, amitriptyline, and citalopram) at different concentrations. The growth inhibition was measured. Results showed that the toxicity of this mixture was higher than the effects of each individual component, highlighting simple additivity or synergistic effects, whereas tested concentrations were below the 10% inhibition concentration (IC 10 ) of each compound. Moreover, the QSAR analysis highlighted that antidepressants would act through narcosis (non-specific mode of action) towards the two species of algae. However, more specific effects can be observed by differentiating compounds with a primary/secondary amine from those with a tertiary amine. These mixture effects on algal species have to be assessed, especially since any impacts on phytoplankton could ultimately impact higher trophic levels (less food, secondary poisoning). Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice.

    Science.gov (United States)

    Mao, Qing-Qiu; Huang, Zhen; Zhong, Xiao-Ming; Xian, Yan-Fang; Ip, Siu-Po

    2014-03-15

    Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair. This study aimed to investigate the role of brain-derived neurotrophic factor (BDNF) signalling in the antidepressant-like effect of piperine in mice exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. It was also found that BDNF protein expression in the hippocampus and frontal cortex were significantly decreased in CUMS-treated mice. Chronic treatment of piperine at the dose of 10mg/kg significantly ameliorated behavioural deficits of CUMS-treated mice in the sucrose preference test and forced swim test. Piperine treatment also significantly decreased immobility time in the forced swim test in naive mice. In parallel, chronic piperine treatment significantly increased BDNF protein expression in the hippocampus and frontal cortex of both naive and CUMS-treated mice. In addition, inhibition of BDNF signalling by injection of K252a, an inhibitor of the BDNF receptor TrkB, significantly blocked the antidepressant-like effect of piperine in the sucrose preference test and forced swim test of CUMS-treated mice. Taken together, this study suggests that BDNF signalling is an essential mediator for the antidepressant-like effect of piperine. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Ketamine: A New Antidepressant?

    Directory of Open Access Journals (Sweden)

    Feride Karacaer

    2015-03-01

    Full Text Available Standart antidepressants are needed for the many individuals with major depressive disorder. However they do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent studies show that subanesthetic dose of ketamine is efficacy and safety for the treatment of depression. Antidepressant effects of ketamine have been found to be short-lived and its psychotomimetic properties may limit the use of ketamine to depressive patients. Future research studies should focus on identifying predictors of response (pharmalogical and clinical , investigating application of different doses and routes of administration and maintaining antidepressant effect. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(1: 30-40

  10. Stopping antidepressants

    African Journals Online (AJOL)

    years of treatment in a cohort study.7 The disproportionately high impact of another depressive episode in late life also has to be considered, and although antidepressants take longer to work in old age, the number needed to treat is three in order to prevent a further relapse. Therefore, careful consideration should be given ...

  11. Pro-inflammatory cytokines as predictors of antidepressant effects of exercise in major depressive disorder.

    Science.gov (United States)

    Rethorst, C D; Toups, M S; Greer, T L; Nakonezny, P A; Carmody, T J; Grannemann, B D; Huebinger, R M; Barber, R C; Trivedi, M H

    2013-10-01

    Exercise is an efficacious treatment for major depressive disorder (MDD) and has independently been shown to have anti-inflammatory effects in non-depressed subjects. Patients with MDD have elevated inflammatory cytokines but it is not known if exercise affects inflammation in MDD patients and whether these changes are clinically relevant. In the TReatment with Exercise Augmentation for Depression (TREAD) study, participants who were partial responders to a selective serotonin reuptake inhibitor were randomized to receive one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW), or 4 KKW for 12 weeks. Blood samples were collected before initiation and again at the end of the 12-week exercise intervention. Serum was analyzed using a multiplexed ELISA for interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher baseline levels of TNF-α were associated with greater decrease in depression symptoms over the 12-week exercise period (Pdepression symptom scores was observed (P=0.04). There were no significant changes in mean level of any cytokine following the 12-week intervention, and no significant relationship between exercise dose and change in mean cytokine level. Results suggest that high TNF-α may differentially predict better outcomes with exercise treatment as opposed to antidepressant medications for which high TNF-α is linked to poor response. Our results also confirm findings from studies of antidepressant medications that tie decreasing IL-1β to positive depression treatment outcomes.

  12. Antidepressant-like drug effects in juvenile and adolescent mice in the tail suspension test: Relationship with hippocampal serotonin and norepinephrine transporter expression and function.

    Directory of Open Access Journals (Sweden)

    Nathan C Mitchell

    2013-10-01

    Full Text Available Depression is a major health problem for which most patients are not effectively treated. This problem is further compounded in children and adolescents where only two antidepressants [both selective serotonin reuptake inhibitors (SSRIs] are currently approved for clinical use. Mouse models provide tools to identify mechanisms that might account for poor treatment response to antidepressants. However, there are few studies in adolescent mice and none in juvenile mice. The tail suspension test (TST is commonly used to assay for antidepressant-like effects of drugs in adult mice. Here we show that the TST can also be used to assay antidepressant-like effects of drugs in C57Bl/6 mice aged 21 (juvenile and 28 (adolescent days post-partum (P. We found that the magnitude of antidepressant-like response to the SSRI escitalopram was less in P21 mice than in P28 or adult mice. The smaller antidepressant response of juveniles was not related to either maximal binding (Bmax or affinity (Kd for [3H]citalopram binding to the serotonin transporter (SERT in hippocampus, which did not vary significantly among ages. Magnitude of antidepressant-like response to the tricyclic desipramine was similar among ages, as were Bmax and Kd values for [3H]nisoxetine binding to the norepinephrine transporter (NET in hippocampus. Together, these findings suggest that juvenile mice are less responsive to the antidepressant-like effects of escitalopram than adults, but that this effect is not due to delayed maturation of SERT in hippocampus. Showing that the TST is a relevant behavioral assay of antidepressant-like activity in juvenile and adolescent mice sets the stage for future studies of the mechanisms underlying the antidepressant response in these young populations.

  13. Effect of short-term antidepressant treatment on early maladaptive schemas in patients with major depressive and panic disorder.

    Science.gov (United States)

    Atalay, Hakan; Atalay, Figen; Bağdaçiçek, Sedat

    2011-06-01

    We aimed to investigate the effect of anti-depressant treatment on early maladaptive schemas (EMSs). Eighty patients were self-referred to a psychiatric outpatient clinic and were diagnosed with major depressive disorder (MDD) (n = 40) and panic disorder (PD) (n = 40) according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV-TR). These patients were administered the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI) and the Young Schema Questionnaire-Short Form (YSQ-SF) before and after a 2-month period of antidepressant treatment and were compared with 40 healthy control subjects. Depressive mood states were more likely to activate early maladaptive schemas compared to the anxious mood states, and treating these mood states simply with anti-depressive medications led to significant improvements in the activation of these schemas. We concluded that half of the schemas might be accepted as antidepressant treatment-resistant EMSs, or, in other words, they can be viewed in part as those specific to depressive mood states.

  14. Decreased brain serotonin turnover rate following administration of Sharbat-e-Ahmed Shah produces antidepressant and anxiolytic effect in rats.

    Science.gov (United States)

    Ahmed, Muhammad; Azmat, Aisha

    2017-07-07

    Sharbat-e-Ahmed Shah (SAS) has usually been used in Traditional Unani Medicine (TUM) for depression and insomnia but still not evaluated for its anti-depressant and Neuropharmacological activity. In the present study, a Human dose of SAS (0.6 ml/kg/d) was administered orally to the rats for 15 consecutive days. Antidepressant and anxiolytic were screened scientifically in rats by using Forced swim test and light and dark box test. At the end of study high-performance liquid chromatographic (HPLC) method with electrochemical (EC) detector was used for the measurement of blood and brain tryptophan and brain serotonin levels. The present reported results are according to what is known in TUM, where is prescribed as an antidepressant agent. After the administration, SAS (at a human dose for 15 days) reduced the immobility time in rats analogous to Imipramine (positive control) indicating the antidepressant effect of SAS. In the present study, Diazepam or SAS (0.6 ml/kg/day) treated rats stayed in the illuminated side of the light-dark box, as compare to control rats (Veh, 134.62 ± 4.430 s; SAS 0.6 ml/kg, 192.2 ± 8.11 s; DZP 1.0 mg/kg, 205.21.20 ± 10.26 s, p < 0.05). It was also observed that SAS increased the availability of tryptophan in blood and brain and hence increases 5-hydroxytryptamine (Serotonin: 5HT) in the brain. At the end, it was concluded that SAS contains some active principles which increase the availability of neurochemical (tryptophan and 5HT) and decrease the 5HT turnover rate thus causes antidepressant and anxiolytic effects in experimental animals.

  15. Further evaluation of the neuropharmacological determinants of the antidepressant-like effects of curcumin.

    Science.gov (United States)

    Witkin, Jeffrey M; Leucke, Susan; Thompson, Linda K; Lynch, Renee A; Ding, Chunjin; Heinz, Beverly; Catlow, John T; Gleason, Scott D; Li, Xia

    2013-06-01

    Curcumin, the major constituent of the spice tumeric produces a plethora of biological actions that have translated in vivo into behavioral and neurochemical effects in rodents that are also produced by clinically-used antidepressants. The present study was designed to provide a systematic replication of prior behavioral, pharmacological, and neurochemical experiments. In particular, the ability of curcumin to engender anti-immobility effects in the mouse forced-swim assay was established. Although prior work had shown curcumin to function as an inhibitor of the monoamine metabolizing enzyme, monoamine oxidase (MAO), neither MAOA nor MAOB was inhibitied by curcumin in the present study. Curcumin had also been reported previously to function as a cannabinoid CB1 receptor inverse agonist/antagonist. However, in our hands, curcumin did not potently alter GTP-γ.-35S binding indicative of functional CB1 antagonism (Kb = 2080 nM). Moreover, curcumin was not able to prevent the hypothermic effects of the cannabinoid receptor agonist (-)-cis-3-[2-Hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP 55,940). Nonetheless, the anti-immobility effects of curcumin did not occur in CB1 -/- mice. Finally, a broad array of protein receptors and enzymes were evaluated in vitro for their potential interaction with and/or functional engagement with curcumin. Of the more than 100 targets screened, curcumin had very low potency in most. Of those targets with appreciable activity, curcumin had affinities for the human cloned muscarinic receptor subtypes (Ki = 1.3-3.1 uM). Moreover, the plasma and brain levels of curcumin at behaviorally-active doses were below quantitative limits. Given these findings, it is concluded that the prominent antidepressant-like behavioral effects of curcumin, replicated here and in multiple acute and chronic rodent models detailed in the literature, are the result of as yet undisclosed mechanisms of action. The scientific and

  16. A systematic review for the antidepressant effects of sleep deprivation with repetitive transcranial magnetic stimulation.

    Science.gov (United States)

    Tang, Qing; Li, Guangming; Wang, Anguo; Liu, Tao; Feng, Shenggang; Guo, Zhiwei; Chen, Huaping; He, Bin; McClure, Morgan A; Ou, Jun; Xing, Guoqiang; Mu, Qiwen

    2015-11-14

    Sleep deprivation (SD) and repetitive transcranial magnetic stimulation (rTMS) have been commonly used to treat depression. Recent studies suggest that co-therapy with rTMS and SD may produce better therapeutic effects than either therapy alone. Therefore, this study was to review the current findings to determine if rTMS can augment the therapeutic effects of SD on depression. Embase, JSTOR, Medline, PubMed, ScienceDirect, and the Cochrane Central Register of Controlled Trials were searched for clinical studies published between January 1985 and March 2015 using the search term "rTMS/repetitive transcranial magnetic stimulation AND sleep deprivation AND depress*". Only randomized and sham-controlled trials (RCTs) involving the combined use of rTMS and SD in depression patients were included in this systematic review. The scores of the Hamilton Rating Scale for Depression were extracted as primary outcome measures. Three RCTs with 72 patients that met the inclusion criteria were included for the systematic review. One of the trials reported skewed data and was described alone. The other two studies, which involved 30 patients in the experimental group (SD + active rTMS) and 22 patients in the control group (SD + sham rTMS), reported normally distributed data. The primary outcome measures showed different results among the three publications: two of which showed great difference between the experimental and the control subjects, and the other one showed non-significant antidepressant effect of rTMS on SD. In addition, two of the included studies reported secondary outcome measures with Clinical Global Impression Rating Scale and a self-reported well-being scale which presented good improvement for the depressive patients in the experiment group when compared with the control. The follow-up assessments in two studies indicated maintained results with the immediate measurements. From this study, an overview of the publications concerning the combined use of rTMS and

  17. 17β-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects.

    Science.gov (United States)

    Ibrahim, Weam W; Safar, Marwa M; Khattab, Mahmoud M; Agha, Azza M

    2016-12-01

    The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressants; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17β-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Young adult female Wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated chronically with escitalopram (10mg/kg/day, i.p) alone or with four doses of 17β-estradiol (40μg/kg, s.c) given prior to the behavioral tests. Co-administration of 17β-estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17β-estradiol augmented the modulatory effects of escitalopram on the hippocampal levels of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin receptor 1A, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the brain histopathological architecture, particularly, the hippocampus. The antidepressant effect of 17β-estradiol was abolished by pretreatment with estrogen receptor antagonist, tamoxifen (10mg/kg, p.o). In conclusion, 17β-estradiol-induced antidepressant effect was confined to intracellular estrogen receptors activation. Moreover, 17β-estradiol enhanced escitalopram's efficiency in ameliorating menopausal-like depression, via exerting synergistic neuroprotective and serotonin reuptake transporter modulatory effects, without impeding escitalopram-mediated cognitive

  18. Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants

    Science.gov (United States)

    Li, Dian-Jeng; Tseng, Ping-Tao; Chen, Yen-Wen; Wu, Ching-Kuan; Lin, Pao-Yen

    2016-01-01

    Abstract Bupropion is widely used for treating bipolar disorder (BD), and especially those with depressive mood, based on its good treatment effect, safety profile, and lower risk of phase shifting. However, increasing evidence indicates that the safety of bupropion in BD patients may not be as good as previously thought. The aim of this study was to summarize data on the treatment effect and safety profile of bupropion in the treatment of BD via a meta-analysis. Electronic search through PubMed and ClinicalTrials.gov was performed. The inclusion criteria were: (i) studies comparing changes in disease severity before and after bupropion treatment or articles comparing the treatment effect of bupropion in BD patients with those receiving other standard treatments; (ii) articles on clinical trials in humans. The exclusion criteria were (i) case reports/series, and (ii) nonclinical trials. All effect sizes from 10 clinical trials were pooled using a random effects model. We examined the possible confounding variables using meta-regression and subgroup analysis. Bupropion significantly improved the severity of disease in BD patients (P bupropion and those who received other antidepressants. We could not perform a detailed meta-analysis of every category of antidepressant, nor could we rule out the possible confounding effect of concurrent psychotropics or include all drug side effects. Furthermore, the number of studies recruited in the meta-analysis was relatively small. Our findings reconfirm the benefits of bupropion for the treatment of bipolar depression, which are similar to those of other antidepressants. However, the rate of phase shifting with bupropion usage was not as low compared to other antidepressants as previously thought, which should serve to remind clinicians of the risk of phase shifting when prescribing bupropion to BD patients regardless of the suggestions of current clinical practice guidelines. PMID:27043678

  19. Computational and biological evidences on the serotonergic involvement of SeTACN antidepressant-like effect in mice.

    Directory of Open Access Journals (Sweden)

    Mariana G Fronza

    Full Text Available A series of phenylselanyl-1H-1,2,3-triazole-4-carbonitriles with different substituents were screened for their binding affinity with serotonin transporter (SERT and dopamine transporter (DAT by docking molecular. 5-(4methoxyphenyl-1-(2-(phenylselanylphenyl-1H-1,2,3-triazole-4-carbonitrile (SeTACN exhibited the best conformation with SERT even higher than fluoxetine and serotonin, suggesting a competitive inhibition. SeTACN demonstrated additional affinity to other serotonergic receptors involved in antidepressant effects: 5HT1a, 5HT2a and 5HT3. In another set of experiments, SeTACN led to significant reductions in the immobility time of mice submitted to forced swimming test (FST in the dose range of 0.1- 20mg/kg, suggesting an antidepressant-like effect. The possible mechanism of action was investigated using serotonergic and dopaminergic antagonists. The antidepressant-like effect of SeTACN (0.1mg/kg i.g. was prevented by the pretreatment with WAY100635 (a selective 5HT1a antagonist, ketanserin (a 5HT2a/c antagonist and ondansetron (a selective 5ht3 antagonist, PCPA (an inhibitor of serotonin synthesis but not with SCH23390 (dopaminergic D1 antagonist and sulpiride (D2 antagonist. Sub-effective dose of fluoxetine was able to potentiate the effects of a sub-effective dose of SeTACN in FST. None of the treatments affected locomotor activity in open field test (OFT. These results together, suggest that the SeTACN antidepressant-like effect is mediate, at least in parts, by serotonergic system.

  20. Antidepressant medications and osteoporosis

    DEFF Research Database (Denmark)

    Rizzoli, R; Cooper, C; Reginster, J-Y

    2012-01-01

    Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major...

  1. Comparative Effectiveness of Second-Generation Antidepressants in Reducing the Risk of Dementia in Elderly Nursing Home Residents with Depression.

    Science.gov (United States)

    Bali, Vishal; Holmes, Holly M; Johnson, Michael L; Chen, Hua; Fleming, Marc L; Aparasu, Rajender R

    2016-01-01

    Second-generation antidepressants have been shown to improve cognition and depression symptomatology, which are the major risk factors for dementia; however, little is known about the comparative effectiveness of antidepressants in reducing the risk of dementia. Thus, the objective of this study was to evaluate the long-term comparative effectiveness of different antidepressant classes in reducing the risk of dementia in elderly nursing home residents with depression. Propensity score-adjusted retrospective cohort study. Multistate Minimum Data Set-linked Medicare Parts A, B, and D data files. A total of 25,108 nursing home residents (65 years and older) with a diagnosis of depression and without a dementia diagnosis who were Medicare beneficiaries and new users of selective serotonin reuptake inhibitors (SSRIs; 19,952 [79.5%]), serotonin-norepinephrine reuptake inhibitors (SNRIs; 2381 [9.5%]), or tetracyclic antidepressants (2775 [11.1%]) between 2007 and 2010. New users of SSRIs, SNRIs, and tetracyclics were followed over a 2-year period for the occurrence of dementia. A Cox proportional hazards regression model was used to evaluate the comparative effectiveness of SNRIs and tetracyclics in reducing the risk of dementia, with the SSRI class used as the reference category after controlling for propensity scores and their interactions terms. The unadjusted incidence of dementia was 8.2% for SSRI users, 6.0% for SNRI users, and 7.2% for tetracyclic users. The propensity score-adjusted Cox model did not find any significant difference in the risk of dementia in elderly nursing home residents who used SNRIs (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.84-1.19) or tetracyclics (HR 1.01, 95% CI 0.87-1.17) compared with the SSRI users. This study did not find any significant differences in reducing the risk of dementia among the new users of second-generation antidepressant classes. Further studies are needed to evaluate the profiles of second

  2. Effect of pharmacist intervention on improving antidepressant medication adherence and depression symptomology: A systematic review and meta-analysis.

    Science.gov (United States)

    Readdean, Kevin C; Heuer, Albert J; Scott Parrott, J

    2017-05-22

    Depression is a widespread disease with effective pharmacological treatments, but low medication adherence. Pharmacists play a key role in supporting medication adherence in patients with depression given their accessibility to patients. The aim of this review was to systematically evaluate the impact of pharmacist interventions on adherence to antidepressants and clinical symptomology among adult outpatients with depressive disorders. A systematic review of controlled trials (both randomized and non-randomized) was conducted. Studies were obtained through a search of PubMed, Academic Search Premier, and Cochrane Library databases. Studies which included a pharmacist intervention to improve medication adherence in outpatients age 17 and above with a depressive disorder diagnosis and antidepressant treatment were included. Twelve publications met inclusion criteria, representing a total of 15,087 subjects: 1379 (9%) intervention and 13,708 (91%) control. The interventions in each selected publication included some level of in-person counseling and education to promote antidepressant adherence. The pooled odds ratio for medication adherence at 6 months was 2.50 (95% CI 1.62 to 3.86). There were no significant differences noted in subgroup meta-analyses except study location (US, Middle East or Europe) and setting. Only one of the identified studies reported statistically significant impacts of the pharmacist intervention on patient depression symptoms. The findings suggest that pharmacist interventions can enhance patient adherence to antidepressant medication in adult outpatients. However, this review failed to demonstrate a positive effect of these interventions on clinical symptoms. Additional longitudinal research is recommended to investigate the multidimensional relationships between pharmacist interventions, patient adherence, and clinical outcomes. Pharmacists play a key role in supporting medication adherence in patients with depression given their

  3. Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L.

    Science.gov (United States)

    Machado, Daniele G; Cunha, Mauricio P; Neis, Vivian B; Balen, Grasiela O; Colla, André; Bettio, Luis E B; Oliveira, Agatha; Pazini, Francis Leonardo; Dalmarco, Juliana B; Simionatto, Edésio Luiz; Pizzolatti, Moacir G; Rodrigues, Ana Lúcia S

    2013-01-15

    The aim of this study was to investigate the antidepressant-like effect of fractions from Rosmarinus officinalis L.: ethyl acetate 1 and 2 (AcOEt1 and 2), hexane (HEX), ethanolic (ET), and essential oil-free (EOF) fractions, as well as essential oil, the isolated compounds carnosol and betulinic acid in the tail suspension test, a predictive test of antidepressant activity. Swiss mice were acutely administered by oral route (p.o.) with fractions, essential oil or isolated compounds, 60 min before the tail suspension test or open-field test. All of them produced a significant antidepressant-like effect: AcOEt1, ET, EOF fractions and essential oil (0.1-100mg/kg, p.o); HEX (0.1-10mg/kg, p.o) and AcOEt2 fraction (0.1-1mg/kg, p.o), carnosol (0.01-0.1mg/kg, p.o.) isolated from the HEX fraction and betulinic acid (10mg/kg, p.o.), isolated from the AcOEt1 and AcOEt2 fractions. No psychostimulant effect was shown in the open-field test, indicating that the effects in the tail suspension test are specific. This study suggests that carnosol and betulinic acid could be responsible for the anti-immobility effect of extracts from R. officinalis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Characterisation of phenolic compounds of the ethyl acetate fraction from Tabernaemontana catharinensis and its potential antidepressant-like effect.

    Science.gov (United States)

    Pauleti, Nathielli Nayara; Mello, Jonas; Siebert, Diogo Alexandre; Micke, Gustavo Amadeu; de Albuquerque, Cláudia Almeida Coelho; Alberton, Michele Debiasi; Barauna, Sara Cristiane

    2017-08-01

    This study evaluates the antidepressant-like effect and analysed the qualitative and quantitative 74 phenolic standards of ethyl acetate fraction from Tabernaemontana catharinensis leaves. Acute administration of fraction in mice reduced the immobility time in forced swimming and tail suspension tests confirming its antidepressant-like activity. The anti-immobility effect elicited by this fraction was prevented by the pretreatment of mice with PCPA (100 mg kg -1 ), ketanserin (5 mg kg -1 ), SCH 23,390 (0.05 mg kg -1 ) or yohimbine (1 mg kg -1 ). A sub effective dose of the fraction produced a synergistic effect with fluoxetine (5 mg kg -1 ). Chromatographic analysis identified 4-hydroxybenzoic and p-coumaric acids in the ethyl acetate fraction from T. catharinensis. Capillary electrophoresis presented 7.34 ± 0.02 mg g -1 of p-coumaric acid concentration in the fraction. Therefore, it is possible that antidepressant-like effect elicited by ethyl acetate fraction from T. catharinensis be dependent on the p-coumaric acid.

  5. Rapid and simple methods for quantitative analysis of some antidepressant in pharmaceutical formulations by using first derivative spectrophotometry and HPLC.

    Science.gov (United States)

    Erk, Nevin

    2003-12-01

    Two rapid, simple and accurate first derivative spectrophotometry and HPLC method for the determination of nefazodone hydrochloride and sertraline hydrochloride in pharmaceutical formulations are discussed. The first one is a derivative spectrophotometric procedure and the second one is based on a HPLC method with a UV detector. In the first method, first derivative spectrophotometry, nefazodone hydrochloride or sertraline hydrochloride by measurement of their first derivative signals at 241.8-256.7 nm (peak-to-peak amplitude), or 271.6-275.5 nm (peak-to-peak amplitude), respectively. Calibration graphs were established for 10.0-42.0 microg ml(-1) nefazodone hydrochloride, or 8.0-46.0 microg ml(-1) sertraline hydrochloride. In the other method, HPLC, the UV detection was carried out at 265.0 nm (nefazodone hydrochloride) and 270.0 nm (sertraline hydrochloride). The samples were chromatographed on a Supercosil RP-18 column. The mobile phases were methanol:acetonitrile:phosphate buffer at pH 5.5 (10:50:40 v/v/v) (nefazodone hydrochloride) and methanol:phosphate buffer at pH 4.5 (20:80 v/v) (sertraline hydrochloride). The results obtained from first derivative spectrophotometric method were comparable with those obtained by using HPLC. It was concluded that both the developed methods are equally accurate, sensitive, and precision could be applied directly and easily to the pharmaceutical formulations of nefazodone hydrochloride and sertraline hydrochloride, respectively.

  6. Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents.

    Science.gov (United States)

    Braida, Daniela; Capurro, Valeria; Zani, Alessia; Rubino, Tiziana; Viganò, Daniela; Parolaro, Daniela; Sala, Mariaelvina

    2009-07-01

    Drugs targeting brain kappa-opioid receptors produce profound alterations in mood. In the present study we investigated the possible anxiolytic- and antidepressant-like effects of the kappa-opioid receptor agonist salvinorin A, the main active ingredient of Salvia divinorum, in rats and mice. Experiments were performed on male Sprague-Dawley rats or male Albino Swiss mice. The anxiolytic-like effects were tested by using the elevated plus maze, in rats. The antidepressant-like effect was estimated through the forced swim (rats) and the tail suspension (mice) test. kappa-Opioid receptor involvement was investigated pretreating animals with the kappa-opioid receptor antagonist, nor-binaltorphimine (1 or 10 mgxkg(-1)), while direct or indirect activity at CB(1) cannabinoid receptors was evaluated with the CB(1) cannabinoid receptor antagonist, N-(piperidin-1-yl) -5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, 0.5 or 3 mgxkg(-1)), binding to striatal membranes of naïve rats and assay of fatty acid amide hydrolase in prefrontal cortex, hippocampus and amygdala. Salvinorin A, given s.c. (0.001-1000 microgxkg(-1)), exhibited both anxiolytic- and antidepressant-like effects that were prevented by nor-binaltorphimine or AM251 (0.5 or 3 mgxkg(-1)). Salvinorin A reduced fatty acid amide hydrolase activity in amygdala but had very weak affinity for cannabinoid CB(1) receptors. The anxiolytic- and antidepressant-like effects of Salvinorin A are mediated by both kappa-opioid and endocannabinoid systems and may partly explain the subjective symptoms reported by recreational users of S. divinorum.

  7. Potentiation of the antidepressant-like effect of desipramine or reboxetine by metyrapone in the forced swimming test in rats.

    Science.gov (United States)

    Rogóz, Zofia

    2009-01-01

    The obtained results revealed that joint administration of desipramine or reboxetine and metyrapone (a glucocorticoid synthesis inhibitor) had more potent antidepressant-like activity in the forced swimming test (FST) in rats compared to treatment with either drug alone. WAY100636 (a 5-HT(1A) antagonist), and prazosin (an alpha(1)-adrenergic antagonist), used in doses ineffective in the FST, inhibited the antidepressant-like effect induced by co-administration of desipramine (10 mg/kg) or reboxetine (10 mg/kg) and metyrapone (50 mg/kg). The above-mentioned findings suggest that, among other mechanisms, the 5-HT(1A) and alpha(1)-adrenergic receptors may play a role in this effect. Furthermore, they may be of particular importance to the pharmacotherapy of drug-resistant depression.

  8. The role of neuropeptide-Y in nandrolone decanoate-induced attenuation of antidepressant effect of exercise.

    Directory of Open Access Journals (Sweden)

    Jovana Joksimovic

    Full Text Available Since the increased prevalence of anabolic androgenic steroids abuse in last few decades is usually accompanied by various exercise protocols, the scope of our study was to evaluate the effects of chronic nandrolone decanoate administration in supraphysiological dose and a prolonged swimming protocol (alone and simultaneously with nandrolone decanoate on depressive state in male rats. Simultaneously, we investigated the possible alterations in neuropeptide Y (NPY content in blood and the hippocampus, in order to determine the role of NPY in the modulation of depressive-like behavior.Exercise induced antidepressant effects in tail suspension test (decrease of the total duration of immobility, as well as significant increase in the number of hippocampal NPY-interneurons in CA1 region. Chronic nandrolone decanoate treatment attenuated the beneficial antidepressant effects of exercise as measured by the tail suspension test parameters. Simultaneously, nandrolone decanoate treatment resulted in diminution of NPY content both in blood (decreased serum levels and in hippocampus (the significant decrease in NPY expression in all three investigated hippocampal regions-CA1, CA2/3 and DG. Our findings indicate that alterations in serum and hippocampal NPY contents may underlie the changes in depressive state in rats. The exercise was beneficial as it exerted antidepressant effect, while chronic nandrolone decanoate treatment resulted in depressive-like behavior. Furthermore, the behavioral indicators of depression showed strong correlations with the serum levels and the hippocampal content of NPY.

  9. Inulin-Type Oligosaccharides Extracted from Yacon Produce Antidepressant-Like Effects in Behavioral Models of Depression.

    Science.gov (United States)

    An, Lei; Yang, Ji-Chu; Yin, Hang; Xue, Rui; Wang, Qiong; Sun, Yu Chen; Zhang, You-Zhi; Yang, Ming

    2016-12-01

    Yacon (Smallanthus sonchifolius), a traditional food in the Andean diet, is attracting global attention for its medicinal properties, which are mainly because of its high content of non-digestible oligosaccharides. The purpose of this study is to evaluate the antidepressant-like effects of inulin-type oligosaccharides extracted from yacon (YOs) in behavioral models of depression. Behavioral despair models in mice including the tail suspension test (TST) and the forced swimming test (FST) were used to determine the effects of acute YOs administration. The locomotor activity was also explored to eliminate any false-positive activity. In addition, to further investigate the antidepressant-like effects of subchronic YOs administration, the learned helplessness (LH) paradigm in rats was performed. The results demonstrated that YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reduced the immobility time in the mouse TST and FST in a U-shaped, dose-dependent manner, and showed no stimulatory effect on the locomotor activity. Furthermore, subchronic YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reversed the escape deficits in LH rats, including an increased number of escape failures and prolonged escape latency. These findings suggest that the inulin-type oligosaccharides extracted from yacon may be a prospective natural source for antidepressants. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats.

    Science.gov (United States)

    Xu, Ying; Ku, Bao-Shan; Yao, Hai-Yan; Lin, Yan-Hua; Ma, Xing; Zhang, Yong-He; Li, Xue-Jun

    2005-09-01

    Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicinal formula, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and we hypothesized that curcumin would have an influence on depressive-like behaviors. The purpose of the present study was to confirm the putative antidepressant effect of chronic administrations of curcumin (1.25, 2.5, 5 and 10 mg/kg, p.o.) in the forced swimming test and bilateral olfactory bulbectomy (OB) models of depression in rats. In the first study, chronic treatment with curcumin (14 days) reduced the immobility time in the forced swimming test. In the second experiment, curcumin reversed the OB-induced behavioral abnormalities such as hyperactivity in the open field, as well as deficits in step-down passive avoidance. In addition, OB-induced low levels of serotonin (5-HT), noradrenaline (NA), high 5-hydroxyindoleacetic acid (5-HIAA) and 4-dihydroxyphenylacetic acid (DOPAC) in the hippocampus were observed, and were completely reversed by curcumin administration. A slight decrease in 5-HT, NA and dopamine (DA) levels was found in the frontal cortex of OB rats which was also reversed by curcumin treatment. These results confirm the antidepressant effects of curcumin in the forced swim and the OB models of depression in rats, and suggest that these antidepressant effects may be mediated by actions in the central monoaminergic neurotransmitter systems.

  11. The effect of flexible cognitive-behavioural therapy and medical treatment, including antidepressants on post-traumatic stress disorder and depression in traumatised refugees

    DEFF Research Database (Denmark)

    Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstrøm, Morten

    2016-01-01

    BACKGROUND: Little evidence exists on the treatment of traumatised refugees. AIMS: To estimate treatment effects of flexible cognitive-behavioural therapy (CBT) and antidepressants (sertraline and mianserin) in traumatised refugees. METHOD: Randomised controlled clinical trial with 2 × 2 factorial...

  12. Antidepressant-like Effect of l-perillaldehyde in Stress-induced Depression-like Model Mice through Regulation of the Olfactory Nervous System

    National Research Council Canada - National Science Library

    Ito, N; Nagai, T; Oikawa, T; Yamada, H; Hanawa, T

    2011-01-01

    ...) medicines that are used clinically for the improvement of depressive mood. l-Perillaldehyde (PAH) is a major component in the essential oil containing in Perillae Herba, but its antidepressant-like effect has not been reported...

  13. Antidepressant-like effects of an apolar extract and chow enriched with Nepeta cataria (catnip) in mice

    OpenAIRE

    Bernardi, Maria Martha; Kirsten, Thiago Berti; Salzgeber, Simone Angélica; Ricci, Esther Lopes; Romoff, Paulete; Lago, João Henrique Guilardi; Lourenço, Lygia Mendes

    2010-01-01

    Nepeta cataria (catnip) is a plant used in pet toys and to treat human diseases. Catnip has also been used in the treatment of some depressive disorders. In this paper, we studied the antidepressant, anxiogenic, and motor activity effects of acute and repeated feeding of chow enriched with 10% N. cataria leaves and the acute and repeated administration of apolar and polar extracts of N. cataria leaves in male mice. The results showed that repeated feeding and acute and repeated administration...

  14. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder

    OpenAIRE

    Correll, Christoph U; Detraux, Johan; De Lepeleire, Jan; De Hert, Marc

    2015-01-01

    People with severe mental illness have a considerably shorter lifespan than the general population. This excess mortality is mainly due to physical illness. Next to mental illness-related factors, unhealthy lifestyle, and disparities in health care access and utilization, psychotropic medications can contribute to the risk of physical morbidity and mortality. We systematically reviewed the effects of antipsychotics, antidepressants and mood stabilizers on physical health outcomes in people wi...

  15. Variations: Darwin's finches, sea barnacles and the side effects of antidepressants.

    Science.gov (United States)

    Lieb, Julian

    2008-01-01

    "It may metaphorically be said," Darwin wrote, "that natural selection is daily and hourly scrutinizing, throughout the world, the slightest variations; rejecting those that are bad, preserving and adding up all that are good; silently and insensibly working, whenever and wherever opportunity offers..." Variation is a principle of nature, without which natural selection could not operate, and life exist. Darwin believed that natural selection would make nature "more and more diversified." Variation occurs in the clutch sizes of birds, the color of hair and skin, the annual temperature, in language and speech, the direction of local Magnetic North and True North, and the variation of pathogens (antigenic variation). Antidepressants act as probes, burrowing into the deepest recesses of cells, and signaling physiological and pathological information to observers. They have at least forty side effects that are not only variations, but often paradoxes that would have fascinated Charles Darwin, who had the keenest interest in the variation of the beaks of finches and in sea barnacles.

  16. Disruption of running activity rhythm following restricted feeding in female mice: Preventive effects of antidepressants

    Directory of Open Access Journals (Sweden)

    Kazumi Miyawaki

    2015-03-01

    Full Text Available Biological rhythms are critical in the etiology of mood disorders; therefore, effective mood disorder treatments should address rhythm disturbances. Among the variables synchronized with the light–dark cycle, spontaneous activity in rodents is useful for investigating circadian rhythms. However, previous studies have focused only on the increase of wheel-running activity under restricted feeding conditions, while little information is available on circadian rhythm of running activity. In this study, chronometrical analysis was used to assess whether circadian rhythms during wheel-running are altered by restricted feeding and affected by antidepressant drugs. Wheel revolutions were automatically recorded and analyzed using cosinor-rhythmometry in 8-week old ICR albino mice. When feeding was restricted to 1 h per day (21:00–22:00, wheel-running rhythms were reliably disrupted. Female mice exhibited marked alterations in the pattern and extent of wheel-running beginning on day 1. Subchronic treatment with imipramine or paroxetine, as well as tandospirone and (−-DOI, prevented wheel-running rhythm disruption. Thus, altering the circadian activity rhythms of female mice on a 1-h feeding schedule may be useful for investigating disturbances in biological rhythms.

  17. Antidepressant-like effects of a water-soluble extract from the culture medium of Ganoderma lucidum mycelia in rats.

    Science.gov (United States)

    Matsuzaki, Hirokazu; Shimizu, Yuta; Iwata, Naohiro; Kamiuchi, Shinya; Suzuki, Fumiko; Iizuka, Hiroshi; Hibino, Yasuhide; Okazaki, Mari

    2013-12-26

    Ganoderma lucidum is a popular medicinal mushroom used for promoting health and longevity in Asian countries. Previously, we reported that a water-soluble extract from a culture medium of Ganoderma lucidum mycelia (MAK) exerts antioxidative and cerebroprotective effects against ischemia-reperfusion injury in vivo. Here, we evaluated the antidepressant and anxiolytic activities of MAK in rats. MAK (0.3 or 1 g/kg, p.o.) was administered in the experimental animals 60 min before the forced swimming, open-field, elevated plus-maze, contextual fear-conditioning, and head twitch tests. Additionally, the mechanisms involved in the antidepressant-like action of MAK were investigated by the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP)- or 5-HT2A agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI)-induced head twitch responses. Treatment with MAK (1 g/kg) exhibited antidepressant-like effects in the forced swimming test, attenuated freezing behavior in the contextual fear-conditioning test, and decreased the number of head twitches induced by DOI, but not with 5-HTP. No significant response was observed in locomotion or anxiety-like behavior, when the animals were evaluated in the open-field or elevated plus-maze test, respectively. These data suggest that MAK has antidepressant-like potential, which is most likely due to the antagonism of 5-HT2A receptors, and possesses anxiolytic-like effects toward memory-dependent and/or stress-induced anxiety in rats.

  18. Paradoxical antidepressant effects of alcohol are related to acid sphingomyelinase and its control of sphingolipid homeostasis.

    Science.gov (United States)

    Müller, Christian P; Kalinichenko, Liubov S; Tiesel, Jens; Witt, Matthias; Stöckl, Thomas; Sprenger, Eva; Fuchser, Jens; Beckmann, Janine; Praetner, Marc; Huber, Sabine E; Amato, Davide; Mühle, Christiane; Büttner, Christian; Ekici, Arif B; Smaga, Irena; Pomierny-Chamiolo, Lucyna; Pomierny, Bartosz; Filip, Malgorzata; Eulenburg, Volker; Gulbins, Erich; Lourdusamy, Anbarasu; Reichel, Martin; Kornhuber, Johannes

    2017-03-01

    Alcohol is a widely consumed drug that can lead to addiction and severe brain damage. However, alcohol is also used as self-medication for psychiatric problems, such as depression, frequently resulting in depression-alcoholism comorbidity. Here, we identify the first molecular mechanism for alcohol use with the goal to self-medicate and ameliorate the behavioral symptoms of a genetically induced innate depression. An induced over-expression of acid sphingomyelinase (ASM), as was observed in depressed patients, enhanced the consumption of alcohol in a mouse model of depression. ASM hyperactivity facilitates the establishment of the conditioned behavioral effects of alcohol, and thus drug memories. Opposite effects on drinking and alcohol reward learning were observed in animals with reduced ASM function. Importantly, free-choice alcohol drinking-but not forced alcohol exposure-reduces depression-like behavior selectively in depressed animals through the normalization of brain ASM activity. No such effects were observed in normal mice. ASM hyperactivity caused sphingolipid and subsequent monoamine transmitter hypo-activity in the brain. Free-choice alcohol drinking restores nucleus accumbens sphingolipid- and monoamine homeostasis selectively in depressed mice. A gene expression analysis suggested strong control of ASM on the expression of genes related to the regulation of pH, ion transmembrane transport, behavioral fear response, neuroprotection and neuropeptide signaling pathways. These findings suggest that the paradoxical antidepressant effects of alcohol in depressed organisms are mediated by ASM and its control of sphingolipid homeostasis. Both emerge as a new treatment target specifically for depression-induced alcoholism.

  19. Antidepressant-like effect of Lafoensia pacari A. St.-Hil. ethanolic extract and fractions in mice.

    Science.gov (United States)

    Galdino, P M; Nascimento, M V M; Sampaio, B L; Ferreira, R N; Paula, J R; Costa, E A

    2009-07-30

    Lafoensia pacari A. St.-Hil. (Lythraceae) has been referred in Brazilian traditional medicine for the treatment of different diseases, among them depression. Nevertheless, there are not studies about this possible effect on the central nervous system (CNS). To evaluate the antidepressant-like effects of the ethanolic extract of Lafoensia pacari (PEtExt) and its fractions on the performance of male mice. Antidepressant activity was studied using forced swimming (FST) and tail suspension (TST) tests, and motor activity in the open-field test. The ethanolic extract of Lafoensia pacari (PEtExt) were administered acutely (1.0 g/kg, p.o.), for 21 days (100, 300 mg, and 1.0 g/(kg day), p.o.), three administration in a 24-h period (1.0 g/kg, p.o.), and the fractions for 21 days. Imipramine (15 mg/(kg day), p.o.) was used as the control positive. The PEtExt significantly reduced immobility time in FST and TST, without affecting the motor activity. Only the chloroformic fraction (50 mg/(kg day), p.o.) increase the latency to immobility and decrease the immobility time in the FST. These data indicate that the extract of Lafoensia pacari A. St.-Hil. possesses antidepressant-like properties in mice.

  20. Antidepressant-Like Effects of Lindera obtusiloba Extracts on the Immobility Behavior of Rats in the Forced Swim Test

    Directory of Open Access Journals (Sweden)

    Dong Wook Lim

    2016-02-01

    Full Text Available Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited antidepressant-like activity in rats subjected to forced swim test (FST-induced depression. Acute treatment of rats with L. obtusiloba extracts (200 mg/kg, p.o. significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with L. obtusiloba extracts also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hippocampus CA3 region. In addition, L. obtusiloba extracts, at concentrations that were not affected by cell viability, significantly decreased luciferase activity in response to cortisol in a concentration-dependent manner by the glucocorticoid binding assay in HeLa cells. Our findings suggested that the antidepressant-like effects of L. obtusiloba extracts were likely mediated via the glucocorticoid receptor (GR. Further studies are needed to evaluate the potential of L. obtusiloba extracts as an alternative therapeutic approach for the treatment of depression.

  1. Learning and memory in the forced swimming test: effects of antidepressants having varying degrees of anticholinergic activity.

    Science.gov (United States)

    Enginar, Nurhan; Yamantürk-Çelik, Pınar; Nurten, Asiye; Güney, Dilvin Berrak

    2016-07-01

    The antidepressant-induced reduction in immobility time in the forced swimming test may depend on memory impairment due to the drug's anticholinergic efficacy. Therefore, the present study evaluated learning and memory of the immobility response in rats after the pretest and test administrations of antidepressants having potent, comparatively lower, and no anticholinergic activities. Immobility was measured in the test session performed 24 h after the pretest session. Scopolamine and MK-801, which are agents that have memory impairing effects, were used as reference drugs for a better evaluation of the memory processes in the test. The pretest administrations of imipramine (15 and 30 mg/kg), amitriptyline (7.5 and 15 mg/kg), trazodone (10 mg/kg), fluoxetine (10 and 20 mg/kg), and moclobemide (10 and 20 mg/kg) were ineffective, whereas the pretest administrations of scopolamine (0.5 mg/kg) and MK-801 (0.1 mg/kg) decreased immobility time suggesting impaired "learning to be immobile" in the animals. The test administrations of imipramine (30 mg/kg), amitriptyline (15 mg/kg), moclobemide (10 mg/kg), scopolamine (0.5 and 1 mg/kg), and MK-801 (0.1 mg/kg) decreased immobility time, which suggested that the drugs exerted antidepressant activity or the animals did not recall that attempting to escape was futile. The test administrations of trazodone (10 mg/kg) and fluoxetine (10 and 20 mg/kg) produced no effect on immobility time. Even though the false-negative and positive responses made it somewhat difficult to interpret the findings, this study demonstrated that when given before the pretest antidepressants with or without anticholinergic activity seemed to be devoid of impairing the learning process in the test.

  2. Curcumin produces antidepressant effects via activating MAPK/ERK-dependent brain-derived neurotrophic factor expression in the amygdala of mice.

    Science.gov (United States)

    Zhang, Lin; Xu, Tianyuan; Wang, Shuang; Yu, Lanqing; Liu, Dexiang; Zhan, Renzhi; Yu, Shu Yan

    2012-11-01

    The potential antidepressant effects of curcumin have been demonstrated in various animal models of depression, however, there is little information regarding the site and mechanisms of curcumin in promoting antidepressant effects. The present study attempts to explore the mechanisms underlying the antidepressant-like action of curcumin by measuring the contents of brain derived neurotrophic factor (BDNF) in the amygdala of animal model of depression. The results showed that treatment with curcumin (40 mg/kg, i.p.) significantly reduced depressive-like behaviors of mice in the forced swim test. Chronic administration of curcumin (40 mg/kg, i.p., 21 days) increased BDNF protein levels in the amygdala and this enhancement was suppressed by pretreatment with the extracellular signal-regulated kinase (ERK) inhibitor SL327. Additionally, the increased levels of ERK phosphoryation in the amygdala by curcumin were blocked by the ERK inhibitor, and inhibition of this kinase prevented the antidepressant effects of curcumin. All of these effects of curcumin, were essentially identical to that observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of curcumin in the forced swim test are mediated, at least in part, by an ERK-regulated increase of BDNF expression in the amygdala of mice. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Antidepressants for Children and Teens

    Science.gov (United States)

    ... Agitation or restlessness New or worsening anxiety or panic attacks Irritability Increasing sadness or worsening of depression ... symptoms or side effects referred to as discontinuation syndrome. Most children who take antidepressants for depression will ...

  4. Antidepressant effects of Kai-Xin-San in fluoxetine-resistant depression rats

    Directory of Open Access Journals (Sweden)

    X.Z. Dong

    2017-08-01

    Full Text Available This study aimed to investigate the antidepressant effect and the mechanism of action of Kai-Xin-San (KXS in fluoxetine-resistant depressive (FRD rats. Two hundred male Wistar rats weighing 200±10 g were exposed to chronic and unpredictable mild stresses (CUMS for 4 weeks and given fluoxetine treatment simultaneously. The rats that did not show significant improvement in behavioral indexes were chosen as the FRD model rats. These rats were randomly divided into four groups: FRD model control; oral fluoxetine and aspirin; oral KXS at a dose of 338 mg·kg–1·day–1; and oral KXS at a dose of 676 mg·kg–1·day–1. Rats continued to be exposed to CUMS and underwent treatment once a day for 3 weeks, then cytokine (COX-2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, TGF-β, and TNF-α levels in the hippocampus and serum, and organ coefficients were measured. Both doses of KXS improved the crossing and rearing frequencies, sucrose-preference index, and body weight in FRD rats. KXS at a dose of 338 mg·kg–1·day–1reduced COX-2, IL-2, IL-6, TNF-α levels, increased IL-10 level in the hippocampus, and reduced IL-2 and TNF-α levels in serum. KXS at a dose of 676 mg·kg–1·day–1reduced TNF-α level in the hippocampus, reduced IL-2 and TNF-α levels in serum, and increased IFN-γ and IL-10 levels in the hippocampus and serum. There were no significant differences in organ-coefficients of the spleen among and between groups. The results suggested that oral administration of KXS in FRD rats was effective in improving behavior disorders by influencing various inflammatory pathways.

  5. Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?

    OpenAIRE

    Pacher, Pal; Kecskemeti, Valeria

    2004-01-01

    The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na+, Ca2+ and K+ channels often leading to life-threatening arrhythmia.

  6. Anti-depressant effect of Paeonia lactiflora Pall extract in rats

    African Journals Online (AJOL)

    Depression is a major disease affecting nearly 13. - 20 % of the population [1]. In spite of the introduction of the tricyclic antidepressants. (TCAs), selective reversible inhibitors of monoamine oxidize A (RIMAs), selective serotonin reuptake inhibitors (SSRIs) and specific serotonin-noradrenaline reuptake inhibitors (SNRIs) ...

  7. EFFECTS OF ANTIDEPRESSANTS ON COGNITIVE-FUNCTIONING OF ELDERLY PATIENTS - A REVIEW

    NARCIS (Netherlands)

    KNEGTERING, H; EIJCK, M; HUIJSMAN, A

    The influence of antidepressants on cognitive performance in elderly patients has been investigated in 18 studies. More than 70 different psychological tests or batteries of tests could be identified in these studies. The tentative conclusions that can be drawn are as follows. Monoamine oxidase

  8. Antidepressant, anxiolytic, and anticataleptic effects of aqueous leaf extract of Antiaris toxicaria Lesch. (Moraceae) in mice: possible mechanisms of actions.

    Science.gov (United States)

    Agbaje, Esther O; Ishola, Ismail O; Oniyire, Joel A

    2014-02-27

    Abstract Background: The leaves of Antiaris toxicaria Lesch. (Moraceae) are used by traditional medicine practitioners in southwest Nigeria in the management of epilepsy, wounds, and neurological disorders. Hence, this study was undertaken to investigate the effect of the aqueous leaf extract of A. toxicaria on the central nervous system. Methods: One hour after administration of A. toxicaria [50-300 mg/kg orally (p.o.)], its antidepressant effect was evaluated using the forced swimming test (FST), anxiolytic effect using elevated plus maze (EPM) test, and anticataleptic effect using haloperidol-induced catalepsy, whereas its effects on hypnosis and motor coordination were studied using hexobarbitone-induced sleeping time and open-field tests, respectively, in mice. Results: Antiaris toxicaria (300 mg/kg) significantly increased swimming activity (36.88%) and reduced immobility time (38.54%). Pretreatment of mice with prazosin (an α1-adrenoceptor antagonist), sulpiride (a D2 receptor antagonist), and l-NG-nitro-arginine (nitric oxide synthase inhibitor) 15 min before A. toxicaria (300 mg/kg p.o.) treatment significantly prevented its antidepressant-like effect by 35.58%, 53.30%, and 56.11%, respectively, in the FST. However, pretreatment with metergoline (5-HT2 receptor antagonist), and atropine (muscarinic cholinergic antagonist) failed to reverse this effect. Interestingly, A. toxicaria (50 mg/kg) significantly increased open-arm exploration in the EPM by 70.31%, which was reversed by 82.66% in the presence of flumazenil [3 mg/kg intraperitoneally (i.p.)]. Haloperidol (1 mg/kg i.p.) induced cataleptic behavior in mice, which was reversed by A. toxicaria (300 mg/kg) (ptoxicaria possesses an antidepressant-like effect involving interaction with α1-adrenoceptor, D2 dopamine receptor, and nitrergic pathway; an anxiolytic-like effect linked to the benzodiazepine system; and a neuroprotective effect.

  9. Evidence of low dose effects of the antidepressant fluoxetine and the fungicide prochloraz on the behavior of the keystone freshwater invertebrate Gammarus pulex.

    Science.gov (United States)

    De Castro-Català, N; Muñoz, I; Riera, J L; Ford, A T

    2017-12-01

    In recent years, behavior-related endpoints have been proposed as rapid and reliable ecotoxicological tools for risk assessment. In particular, the use of detritivores to test the toxicity of pollutants through feeding is currently becoming a well-known method. Experiments combining feeding with other behavioral endpoints can provide relevant information about direct and indirect toxicological effects of chemicals. We carried out a feeding experiment with the shredder Gammarus pulex in order to detect indirect (through leaf conditioning) and direct effects (through water exposure) of two pollutants at environmentally relevant concentrations: the fungicide prochloraz (6 μg/L) and the antidepressant fluoxetine (100 ng/L). Prochloraz inhibited fungal growth on leaves, but it did not affect either the microbial breakdown rates or the C:N ratio of the leaves. Individuals of G. pulex that were fed with treated leaves presented lower consumption rates, not only those fed with prochloraz-treated leaves, but also those fed with fluoxetine-treated leaves, and those fed with the mixture-treated leaves. Mixed-effects models revealed that the swimming velocity of the amphipods after the experiment was modulated by the exposure to fluoxetine, and also by the exposure to prochloraz. We demonstrate that both the antidepressant and the fungicide may cause significant sublethal effects at low concentrations. The combination of behavioral endpoints together with the application of mixed models provided a useful tool for early detection of the effects of toxicity mixtures in freshwater ecosystems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Benzodiazepines And The Potential Trophic Effect Of Antidepressants On Dentate Gyrus Cells In Mood Disorders

    Science.gov (United States)

    Boldrini, Maura; Butt, Tanya H.; Santiago, Adrienne N.; Tamir, Hadassah; Dwork, Andrew J.; Rosoklija, Gorazd B.; Arango, Victoria; Hen, René; Mann, J. John

    2015-01-01

    Modest antidepressant response rates of mood disorders (MD) encourage benzodiazepine (BZD) co-medication with debatable benefit. Adult hippocampal neurogenesis may underlie antidepressant responses, but diazepam co-administration impairs murine neuron maturation and survival in response to fluoxetine. We counted neural progenitor cells (NPCs), mitotic cells, and mature granule neurons postmortem in dentate gyrus (DG) from subjects with: untreated DSM-IV MD (n=17); antidepressant-treated MD (MD*ADT, n=10); benzodiazepine-antidepressant-treated MD (MD*ADT*BZD, n=7); no psychopathology or treatment (controls, n=18). MD*ADT*BZD had fewer granule neurons vs. MD*ADT in anterior DG and vs. controls in mid DG, and did not differ from untreated-MD in any DG subregion. MD*ADT had more granule neurons than untreated-MD in anterior and mid DG and comparable granule neuron number to controls in all dentate subregions. Untreated-MD had fewer granule neurons than controls in anterior and mid DG, and did not differ from any other group in posterior DG. MD*ADT*BZD had fewer NPCs vs. MD*ADT in mid DG. MD*ADT had more NPCs vs. untreated-MD and controls in anterior and mid DG. MD*ADT*BZD and MD*ADT had more mitotic cells in anterior DG vs. controls and untreated-MD. There were no between-group differences in mid DG in mitotic cells or in posterior DG for any cell type. Our results in mid-dentate, and to some degree anterior dentate, gyrus are consistent with murine findings that benzodiazepines counteract antidepressant-induced increases in neurogenesis by interfering with progenitor proliferation. We also confirmed, in this expanded sample, our previous finding of granule neuron deficit in untreated MD. PMID:24969726

  11. Resting state brain network function in major depression - Depression symptomatology, antidepressant treatment effects, future research.

    Science.gov (United States)

    Brakowski, Janis; Spinelli, Simona; Dörig, Nadja; Bosch, Oliver Gero; Manoliu, Andrei; Holtforth, Martin Grosse; Seifritz, Erich

    2017-09-01

    The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across

  12. Blue again: Perturbational effects of antidepressants suggest monoaminergic homeostasis in major depression

    Directory of Open Access Journals (Sweden)

    Paul eAndrews

    2011-07-01

    Full Text Available Some evolutionary researchers have argued that current diagnostic criteria for major depressive disorder (MDD may not accurately distinguish true instances of disorder from a normal, adaptive stress response. According to disorder advocates, neurochemicals like the monoamine neurotransmitters (serotonin, norepinephrine, and dopamine are dysregulated in major depression. Monoamines are normally under homeostatic control, so the monoamine disorder hypothesis implies a breakdown in homeostatic mechanisms. In contrast, adaptationist hypotheses propose that homeostatic mechanisms are properly functioning in most patients meeting current criteria for MDD. If the homeostatic mechanisms regulating monoamines are functioning properly in these patients, then oppositional tolerance should develop with prolonged antidepressant medication (ADM therapy. Oppositional tolerance refers to the forces that develop when a homeostatic mechanism has been subject to prolonged pharmacological perturbation that attempt to bring the system back to equilibrium. When pharmacological intervention is discontinued, the oppositional forces cause monoamine levels to overshoot their equilibrium levels. Since depressive symptoms are under monoaminergic control, this overshoot should cause a resurgence of depressive symptoms that is proportional to the perturbational effect of the ADM. We test this prediction by conducting a meta-analysis of ADM discontinuation studies. We find that the risk of relapse after ADM discontinuation is positively associated with the degree to which ADMs enhance serotonin and norepinephrine in prefrontal cortex, after controlling for covariates. The results are consistent with oppositional tolerance, and provide no evidence of malfunction in the monoaminergic regulatory mechanisms in patients meeting current diagnostic criteria for MDD. We discuss the evolutionary and clinical implications of our findings.

  13. Agmatine enhances the antidepressant-like effect of lithium in mouse forced swimming test through NMDA pathway.

    Science.gov (United States)

    Mohseni, Gholmreza; Ostadhadi, Sattar; Imran-Khan, Muhammad; Norouzi-Javidan, Abbas; Zolfaghari, Samira; Haddadi, Nazgol-Sadat; Dehpour, Ahmad-Reza

    2017-04-01

    Depression is one the world leading global burdens leading to various comorbidities. Lithium as a mainstay in the treatment of depression is still considered gold standard treatment. Similar to lithium another agent agmatine has also central protective role against depression. Since, both agmatine and lithium modulate various effects through interaction with NMDA receptor, therefore, in current study we aimed to investigate the synergistic antidepressant-like effect of agmatine with lithium in mouse force swimming test. Also to know whether if such effect is due to interaction with NMDA receptor. In our present study we found that when potent dose of lithium (30mg/kg) was administered, it significantly decreased the immobility time. Also, when subeffective dose of agmatine (0.01mg/kg) was coadministered with subeffective dose of lithium (3mg/kg), it potentiated the antidepressant-like effect of subeffective dose of lithium. For the involvement of NMDA receptor in such effect, we administered NMDA receptor antagonist MK-801 (0.05mg/kg) with a combination of subeffective dose of lithium (3mg/kg) and agmatine (0.001mg/kg). A significant antidepressant-like effect was observed. Furthermore, when subeffective dose (50 and 75mg/kg) of NMDA was given it inhibited the synergistic effect of agmatine (0.01mg/kg) with lithium (3mg/kg). Hence, our finding demonstrate that agmatine have synergistic effect with lithium which is mediated by NMDA receptor pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model.

    Directory of Open Access Journals (Sweden)

    Joakim Ramsberg

    Full Text Available OBJECTIVE: To determine effectiveness and cost-effectiveness over a one-year time horizon of pharmacological first line treatment in primary care for patients with moderate to severe depression. DESIGN: A multiple treatment comparison meta-analysis was employed to determine the relative efficacy in terms of remission of 10 antidepressants (citalopram, duloxetine escitalopram, fluoxetine, fluvoxamine mirtazapine, paroxetine, reboxetine, sertraline and venlafaxine. The estimated remission rates were then applied in a decision-analytic model in order to estimate costs and quality of life with different treatments at one year. DATA SOURCES: Meta-analyses of remission rates from randomised controlled trials, and cost and quality-of-life data from published sources. RESULTS: The most favourable pharmacological treatment in terms of remission was escitalopram with an 8- to 12-week probability of remission of 0.47. Despite a high acquisition cost, this clinical effectiveness translated into escitalopram being both more effective and having a lower total cost than all other comparators from a societal perspective. From a healthcare perspective, the cost per QALY of escitalopram was €3732 compared with venlafaxine. CONCLUSION: Of the investigated antidepressants, escitalopram has the highest probability of remission and is the most effective and cost-effective pharmacological treatment in a primary care setting, when evaluated over a one year time-horizon. Small differences in remission rates may be important when assessing costs and cost-effectiveness of antidepressants.

  15. Nocebo effect in randomized clinical trials of antidepressants in children and adolescents: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Johanna Carolina Rojas Mirquez

    2014-11-01

    Full Text Available Objective: To compare the incidence of adverse events between active and placebo arms of randomized clinical trials in depressive children and adolescents with antidepressant treatments, in order to look for similarities in both groups that allow to establish a possible nocebo effect.Methods: Systematic search strategy (January 1974-March 2013 in electronic databases, conference abstracts and reference list of systematic reviews and included studies to identify parallel randomized placebo-controlled trials of antidepressants in children and adolescents (<19 years with Major Depressive Disorder, and one or more interventions of any orally administered antidepressant. The pooled adverse events were calculated based on a fixed-effect model and statistical analysis involved the Risk Ratio (RR of adverse events, with 95% confidence intervals (95%CI.Results: Sixteen studies were included in the review, of which seven studies with a sample of 1911 patients had data to include in the meta-analysis. There was similar risk for the incidence of adverse events between non-active and active group (global Risk Ratio 1.04, 95% Confidence Interval: 0.97-1.11. Conclusions: Depressive children and adolescents allocated to placebo or active group had similar risk to develop adverse events. These similarities in both groups are attributed to the nocebo effect. It is of note that defining nocebo effects is challenging in clinical populations because adverse effects may be attributed to the intervention or may be manifestation of the disease itself. The inclusion of a no treatment arm may be warranted. Nocebo effects are likely when adverse events of placebo mimic the adverse events of active treatment, as was the case here.

  16. Nocebo Effect in Randomized Clinical Trials of Antidepressants in Children and Adolescents: Systematic Review and Meta-Analysis

    Science.gov (United States)

    Rojas-Mirquez, Johanna Carolina; Rodriguez-Zuñiga, Milton Jose Max; Bonilla-Escobar, Francisco Javier; Garcia-Perdomo, Herney Andres; Petkov, Mike; Becerra, Lino; Borsook, David; Linnman, Clas

    2014-01-01

    Objective: To compare the incidence of adverse events between active and placebo arms of randomized clinical trials in depressive children and adolescents (C&A) with antidepressant treatments, in order to look for similarities in both groups that allow to establish a possible nocebo effect. Methods: Systematic search strategy (January 1974–March 2013) in electronic databases, conference abstracts, and reference list of systematic reviews and included studies to identify parallel randomized placebo-controlled trials of antidepressants in C&A (<19 years) with major depressive disorder, and one or more interventions of any orally administered antidepressant. The pooled adverse events were calculated based on a fixed-effect model and statistical analysis involved the risk ratio (RR) of adverse events, with 95% confidence intervals (95% CI). Results: Sixteen studies were included in the review, of which seven studies with a sample of 1911 patients had data to include in the meta-analysis. There was similar risk for the incidence of adverse events between non-active and active group (global RR 1.04, 95% CI: 0.97–1.11). Conclusion: Depressive C&A allocated to placebo or active group had similar risk to develop adverse events. These similarities in both groups are attributed to the nocebo effect. It is of note that defining “nocebo” effects is challenging in clinical populations because adverse effects may be attributed to the intervention or may be manifestation of the disease itself. The inclusion of a no-treatment arm may be warranted. Nocebo effects are likely when adverse events of placebo mimic the adverse events of active treatment, as was the case here. PMID:25404901

  17. Antidepressive and antinociceptive effects of ethanolic extract and fruticuline A from Salvia lachnostachys Benth leaves on rodents.

    Directory of Open Access Journals (Sweden)

    Joyce Alencar Santos

    Full Text Available This study investigated the antidepressant and antinociceptive effects of ethanolic extract (SLEE and pure fruticuline A obtained from Salvia lachnostachys leaves on rats and mice.In this study, SLEE (100 mg/kg, p.o. route was evaluated for its effects on spared nerve injury (SNI in rats. The animals were submitted to mechanical sensitivity, forced swim (FST and cold sensitivity tests 10 and 15 days after surgery. SLEE (100 mg/kg, p.o. and fruticuline A (3 mg/kg, p.o. were also evaluated with respect to nociceptive behavior induced by formalin. In addition, clonidine-induced depressive-like behavior was also analyzed.The oral administration of SLEE for up to 15 days and the subcutaneous injection of 10 mg/kg of ketamine (positive control significantly inhibited SNI-induced mechanical hyperalgesia and decreased immobility in the FST. On the 15th day of oral treatment, SLEE prevented the SNI-induced increase in cold sensitivity. In the formalin test, SLEE and fruticuline A significantly reduced the frequency of paw licking during the first and second phases and decreased the formation of edema. In locomotor analysis (open field test without clonidine treatment, SLEE and fruticuline A did not alter the response. SLEE and fruticuline A significantly attenuated clonidine-induced suppression of spontaneous locomotor activity (squares invaded and licking and emotionality (grooming and freezing compared with controls, similar to the naive group.SLEE exhibits antihyperalgesic, antidepressant, and antinociceptive effects, and fruticuline A appears to be at least partly responsible for the effects of SLEE. Together, these results demonstrate the antidepressive effects of SLEE and fruticuline A and indicate that both derivatives obtained from S. lachnostachys act against spontaneous neuropathic pain.

  18. Comparison of the antidepressant effects of venlafaxine and dosulepin in a naturalistic setting

    DEFF Research Database (Denmark)

    Bukh, Jens Drachmann; Jørgensen, Martin Balslev; Dam, Henrik

    2009-01-01

    The relative efficacy of the various classes of antidepressants has not been established. Observational studies in naturalistic settings are important in evaluating treatment outcomes with antidepressants, since controlled clinical trials include only a minority of patients present in clinical...... practice. This study sought to evaluate in a naturalistic setting the treatment outcomes of dosulepin and venlafaxine for patients with depressive episodes. At the university hospital in Copenhagen, Denmark, between 1998 and early 2001, the first-line treatment for psychiatric inpatients with depression......-hoc analysis suggested that the failure to achieve significant difference was related to a type 2 error. However, missing data and possible confounders related to the different treatment periods weaken the results. This naturalistic study showed a non-significant trend for poorer treatment outcomes (probably...

  19. Effects of neuroleptics displaying antidepressant activity on behavior of rats in the forced swimming test.

    Science.gov (United States)

    Górka, Z; Janus, K

    1985-08-01

    Levomepromazine, thioridazine and cis-chlorprothixene, neuroleptics with antidepressant activity, trans-chlorprothixene, the therapeutically inactive isomer of chlorprothixene, clozapine, an atypical neuroleptic, and imipramine, a classical antidepressant, were studied in the forced swimming test in rats after single or chronic administration. Levomepromazine (1.5 mg/kg), clozapine (2.5 and 5.0 mg/kg) and imipramine (10 mg/kg) after single administration, 1 hr before the test, shortened the period of the immobility. After chronic administration only imipramine (10 mg/kg orally, twice daily, for 10 days) diminished the immobility. Levomepromazine, thioridazine, cis-chlorprothixene and trans-chlorprothixene (1.5 mg, orally, twice daily, for 10 days), 15-18 hr after the last dose did not influence the immobility, although the behavioral parameters in the open field test were not depressed. It is concluded that the forced swimming test is not a suitable pharmacological model for revealing antidepressant activities of certain neuroleptics that are useful in treating certain forms of human depression.

  20. Milnacipran: a unique antidepressant?

    Directory of Open Access Journals (Sweden)

    Siegfried Kasper

    2010-08-01

    Full Text Available Siegfried Kasper, Gerald PailDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, AustriaAbstract: Tricyclic antidepressants (TCAs are among the most effective antidepressants available, although their poor tolerance at usual recommended doses and toxicity in ­overdose make them difficult to use. While selective serotonin reuptake inhibitors (SSRIs are ­better tolerated than TCAs, they have their own specific problems, such as the aggravation of sexual dysfunction, interaction with coadministered drugs, and for many, a discontinuation syndrome. In addition, some of them appear to be less effective than TCAs in more severely depressed patients. Increasing evidence of the importance of norepinephrine in the etiology of depression has led to the development of a new generation of antidepressants, the serotonin and ­norepinephrine reuptake inhibitors (SNRIs. Milnacipran, one of the pioneer SNRIs, was designed from theoretic considerations to be more effective than SSRIs and better tolerated than TCAs, and with a simple pharmacokinetic profile. Milnacipran has the most balanced potency ratio for reuptake inhibition of the two neurotransmitters compared with other SNRIs (1:1.6 for milnacipran, 1:10 for duloxetine, and 1:30 for venlafaxine, and in some studies milnacipran has been shown to inhibit norepinephrine uptake with greater potency than serotonin (2.2:1. Clinical studies have shown that milnacipran has efficacy comparable with the TCAs and is superior to SSRIs in severe depression. In addition, milnacipran is well tolerated, with a low potential for pharmacokinetic drug–drug interactions. Milnacipran is a first-line therapy suitable for most depressed patients. It is frequently successful when other treatments fail for reasons of efficacy or tolerability.Keywords: milnacipran, SNRI, antidepressant efficacy, tolerability

  1. Differentiated effects of the multimodal antidepressant vortioxetine on sleep architecture: Part 2, pharmacological interactions in rodents suggest a role of serotonin-3 receptor antagonism.

    Science.gov (United States)

    Leiser, Steven C; Iglesias-Bregna, Deborah; Westrich, Ligia; Pehrson, Alan L; Sanchez, Connie

    2015-10-01

    Antidepressants often disrupt sleep. Vortioxetine, a multimodal antidepressant acting through serotonin (5-HT) transporter (SERT) inhibition, 5-HT3, 5-HT7 and 5-HT1D receptor antagonism, 5-HT1B receptor partial agonism, and 5-HT1A receptor agonism, had fewer incidences of sleep-related adverse events reported in depressed patients. In the accompanying paper a polysomnographic electroencephalography (sleep-EEG) study of vortioxetine and paroxetine in healthy subjects indicated that at low/intermediate levels of SERT occupancy, vortioxetine affected rapid eye movement (REM) sleep differently than paroxetine. Here we investigated clinically meaningful doses (80-90% SERT occupancy) of vortioxetine and paroxetine on sleep-EEG in rats to further elucidate the serotoninergic receptor mechanisms mediating this difference. Cortical EEG, electromyography (EMG), and locomotion were recorded telemetrically for 10 days, following an acute dose, from rats receiving vortioxetine-infused chow or paroxetine-infused water and respective controls. Sleep stages were manually scored into active wake, quiet wake, and non-REM or REM sleep. Acute paroxetine or vortioxetine delayed REM onset latency (ROL) and decreased REM episodes. After repeated administration, vortioxetine yielded normal sleep-wake rhythms while paroxetine continued to suppress REM. Paroxetine, unlike vortioxetine, increased transitions from non-REM to wake, suggesting fragmented sleep. Next, we investigated the role of 5-HT3 receptors in eliciting these differences. The 5-HT3 receptor antagonist ondansetron significantly reduced paroxetine's acute effects on ROL, while the 5-HT3 receptor agonist SR57227A significantly increased vortioxetine's acute effect on ROL. Overall, our data are consistent with the clinical findings that vortioxetine impacts REM sleep differently than paroxetine, and suggests a role for 5-HT3 receptor antagonism in mitigating these differences. © The Author(s) 2015.

  2. Evidence for the Involvement of Potassium Channel Inhibition in the Antidepressant-Like Effects of Hesperidin in the Tail Suspension Test in Mice.

    Science.gov (United States)

    Donato, Franciele; Borges Filho, Carlos; Giacomeli, Renata; Alvater, Elza Eliza Tenório; Del Fabbro, Lucian; Antunes, Michele da Silva; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Souza, Leandro Cattelan; Boeira, Silvana Peterini; Jesse, Cristiano Ricardo

    2015-07-01

    The administration of hesperidin elicits an antidepressant-like effect in mice by a mechanism dependent on an interaction with the L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, whose stimulation is associated with the activation of potassium (K(+)) channels. Thus, this study investigated the involvement of different types of K(+) channels in the antidepressant-like effect of hesperidin in the mice tail suspension test (TST). The intracerebroventricular administration of tetraethylammonium (TEA, a nonspecific blocker of K(+) channels), glibenclamide (an ATP-sensitive K(+) channel blocker), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel blocker) or apamin (a small-conductance calcium-activated K(+) channel blocker) combined with a subeffective dose of hesperidin (0.01 mg/kg, intraperitoneally [i.p.]) was able to produce a synergistic antidepressant-like effect in the mice TST. Moreover, the antidepressant-like effect elicited by an effective dose of hesperidin (0.3 mg/kg, i.p.) in TST was abolished by the treatment of mice with pharmacological compounds K(+) channel openers (cromakalim and minoxidil). Results showed that the antidepressant-like effect of hesperidin in TST may involve, at least in part, the modulation of neuronal excitability through inhibition of K(+) channels and may act through a mechanism dependent on the inhibition of L-arginine-NO pathway.

  3. Antidepressant-like effects of Gan-Mai-Dazao-Tang via monoamine regulatory pathways on forced swimming test in rats

    Directory of Open Access Journals (Sweden)

    Hsiang-Ling Huang

    2018-01-01

    Full Text Available Depression is a highly prevalent and recurrent mental disorder that impacts all aspects of human life. Undesirable effects of the antidepressant drugs led to the development of complementary and alternative therapies. Gan-Mai-Da-Zao-Tang (甘麥大棗湯, gān mài dà zǎo tang is a traditional herbal formula commonly used for the treatment of depression, but lack of scientific proof on its mechanism. It consisted of Glycyrrhiza uralensis Fisch. (licorice, Triticum aestivum L. (wheat and Zizphus jujuba Mill. (jujube. The objective of this study is to investigate the antidepressant effects of Gan-Mai-Dazao-Tang and its ingredients in rats exposed to forced swimming test (FST. The 72 of male Nerl: Wistar rats (8 weeks old were randomized into control (10 mL/kg bw H2O, licorice (0.4 g/kg bw, wheat (1.6 g/kg bw, jujube (0.5 g/kg bw, Gan-Mai-Da-Zao-Tang (2.5 g/kg bw of licorice: wheat: jujube in ratio of 5:20:6 and Prozac (18 mg/kg bw groups. Samples were administered by oral gavage for 21 days. FST was performed on 21st day, with 15 min for pretest followed by 5 min for real test. Then, the animals were sacrificed and brain tissues were collected for monoamines analyses. The Gan-Mai-Da-Zao-Tang (LWJ showed significantly down-regulation of immobility time, 3,4-dihydroxyphenylacetic acid (DOPAC and DOPAC/dopamine (DA turnover rates, and also enhanced the concentration of serotonin (5-HT and DA in brain tissues, as compared with the control. The LWJ stated the potent antidepressant-like effect by modulating these monoamines concentration, while the licorice, wheat and jujube did not reported significant results as compared with control group. The positive control (Prozac was noted with significantly reduction in body weight and appetite. In conclusion, the antidepressant-like effects of LWJ might be mediated by the regulation of monoamine neurotransmitters. Thus, it could beneficial in depression treatment as a complementary approach.

  4. Role of Monoaminergic System in the Etiology of Olive Oil Induced Antidepressant and Anxiolytic Effects in Rats

    OpenAIRE

    Sadia Saleem; Saiqa Tabassum; Saida Haider; Bilal Moiz Hashmi; Tahira Perveen; Munnawar Ahmed Siddiqui

    2013-01-01

    Olive oil is the major component of the Mediterranean diet and has rich history of nutritional and medicinal uses. In the present study, the antidepressant and anxiolytic effects and their neurochemical basis following repeated administration of extravirgin olive oil were monitored. Male albino Wistar rats were used during study. Animals of test group were given olive oil orally at the dose of 0.25 mL/kg daily for 4 weeks. Control rats received equal volume of water. Elevated-plus maze (EPM) ...

  5. Antidepressant-like effects of Marasmius androsaceus metabolic exopolysaccharides on chronic unpredictable mild stress-induced rat model.

    Science.gov (United States)

    Song, Jia; Wang, Xue; Huang, Yu; Qu, Yidi; Teng, Lesheng; Wang, Di; Meng, Zhaoli

    2017-10-01

    Marasmius androsaceus (M. androsaceus), a medicinal fungus, has various pharmacological activities including antidepression. The present study investigated the effects of exopolysaccharides obtained during M. androsaceus submerged fermentation in a chronic unpredictable mild stress (CUMS)‑induced depression rat model. Similar to fluoxetine (positive drug), 4‑week administration of M. androsaceus exopolysaccharides (MEPS) at doses of 6, 30 and 150 mg/kg strongly enhanced bodyweight gain and sucrose consumption, and reduced the immobility time in forced swimming test and tail suspension test in CUMS rats. MEPS resulted in significant enhancement on the levels of noradrenalin, dopamine, 5‑hydroxytryptamine (5‑HT), and 5‑hydroxyindoleacetic acid in the serum and hypothalamus of CUMS rats, as detected by ELISA. Western blotting results revealed that MEPS upregulated the protein expression levels of tyrosine hydroxylase in the hypothalamus of CUMS rats. In conclusion, these results confirmed the antidepressant‑like effects of MEPS, and suggested that the monoamine neurotransmitter system is involved in its antidepressive effects in a CUMS rat model. The present study provided evidence for the clinical application of MEPS as an effective agent against depression.

  6. Does good leadership buffer effects of high emotional demands at work on risk of antidepressant treatment? A prospective study from two Nordic countries.

    Science.gov (United States)

    Madsen, Ida E H; Hanson, Linda L Magnusson; Rugulies, Reiner; Theorell, Töres; Burr, Hermann; Diderichsen, Finn; Westerlund, Hugo

    2014-08-01

    Emotionally demanding work has been associated with increased risk of common mental disorders. Because emotional demands may not be preventable in certain occupations, the identification of workplace factors that can modify this association is vital. This article examines whether effects of emotional demands on antidepressant treatment, as an indicator of common mental disorders, are buffered by good leadership. We used data from two nationally representative work environment studies, the Danish Work Environment Cohort Study (n = 6,096) and the Swedish Longitudinal Occupational Survey of Health (n = 3,411), which were merged with national registers on antidepressant purchases. All individuals with poor self-reported baseline mental health or antidepressant purchases within 8.7 months before baseline were excluded, and data analysed prospectively. Using Cox regression, we examined hazard ratios (HRs) for antidepressants in relation to the joint effects of emotional demands and leadership quality. Buffering was assessed with Rothman's synergy index. Cohort-specific risk estimates were pooled by random effects meta-analysis. High emotional demands at work were associated with antidepressant treatment whether quality of leadership was poor (HR = 1.84, 95 % CI 1.32-2.57) or good (HR = 1.70, 95 % CI 1.25-2.31). The synergy index was 0.66 (95 % CI 0.34-1.28). Our findings suggest that good leadership does not substantially ameliorate any effects of emotional demands at work on employee mental health. Further research is needed to identify possible preventive measures for this work environment exposure.

  7. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder.

    Science.gov (United States)

    Correll, Christoph U; Detraux, Johan; De Lepeleire, Jan; De Hert, Marc

    2015-06-01

    People with severe mental illness have a considerably shorter lifespan than the general population. This excess mortality is mainly due to physical illness. Next to mental illness-related factors, unhealthy lifestyle, and disparities in health care access and utilization, psychotropic medications can contribute to the risk of physical morbidity and mortality. We systematically reviewed the effects of antipsychotics, antidepressants and mood stabilizers on physical health outcomes in people with schizophrenia, depression and bipolar disorder. Updating and expanding our prior systematic review published in this journal, we searched MEDLINE (November 2009 - November 2014), combining the MeSH terms of major physical disease categories (and/or relevant diseases within these categories) with schizophrenia, major depressive disorder and bipolar disorder, and the three major psychotropic classes which received regulatory approval for these disorders, i.e., antipsychotics, antidepressants and mood stabilizers. We gave precedence to results from (systematic) reviews and meta-analyses wherever possible. Antipsychotics, and to a more restricted degree antidepressants and mood stabilizers, are associated with an increased risk for several physical diseases, including obesity, dyslipidemia, diabetes mellitus, thyroid disorders, hyponatremia; cardiovascular, respiratory tract, gastrointestinal, haematological, musculoskeletal and renal diseases, as well as movement and seizure disorders. Higher dosages, polypharmacy, and treatment of vulnerable (e.g., old or young) individuals are associated with greater absolute (elderly) and relative (youth) risk for most of these physical diseases. To what degree medication-specific and patient-specific risk factors interact, and how adverse outcomes can be minimized, allowing patients to derive maximum benefits from these medications, requires adequate clinical attention and further research. © 2015 World Psychiatric Association.

  8. Subchronic administration of Trichilia catigua ethyl-acetate fraction promotes antidepressant-like effects and increases hippocampal cell proliferation in mice.

    Science.gov (United States)

    Taciany Bonassoli, Vivian; Micheli Chassot, Janaine; Longhini, Renata; Milani, Humberto; Mello, João Carlos P; de Oliveira, Rúbia Maria Weffort

    2012-08-30

    Trichilia catigua preparations have been popularly used in Brazil as a tonic for the treatment of fatigue, stress, impotence, and memory deficits. We recently demonstrated an antidepressant-like effect of acute administration of the Trichilia catigua ethyl-acetate fraction (EAF) in mice. The aim of the present study was to evaluate whether subchronic Trichilia catigua EAF administration maintains its antidepressant-like effects and whether these effects are related to hippocampal neurogenesis. Trichilia catigua EAF (200 and 400mg/kg) was orally administered to mice for 14 day. The animals were tested in the forced swim test (FST) or tail suspension test (TST). After behavioral testing, the animals received bromodeoxyuridine (BrdU; 200mg/kg, i.p.) and were euthanized 24h, 7 day, or 15 day later. The brains were assayed for BrdU and doublecortin (DCX) immunohistochemistry to detect cell proliferation/survival and neurogenesis, respectively. Subchronic administration of 400mg/kg Trichilia catigua EAF promoted antidepressant-like effects in mice in both the FST and TST. The antidepressant-like effect was accompanied by an increase in cell proliferation in the dentate gyrus (DG) of the hippocampus 24h after the treatments were discontinued. This proliferative effect, however, did not influence cell survival or neurogenesis because no change in the number of BrdU- or DCX-positive cells was detected 7 or 15 day after the last EAF administration compared with controls. Trichilia catigua EAF produced antidepressant-like effects and induced hippocampal cell proliferation in mice. The results contribute information on the pharmacological and molecular mechanisms involved in the antidepressant-like effect of Trichilia catigua EAF. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: evidence for the involvement of the serotonergic and noradrenergic systems.

    Science.gov (United States)

    Machado, Daniele G; Bettio, Luis E B; Cunha, Mauricio P; Santos, Adair R S; Pizzolatti, Moacir G; Brighente, Inês M C; Rodrigues, Ana Lúcia S

    2008-06-10

    We have recently shown that the hexanic extract from leaves of Schinus molle produces antidepressant-like effects in the tail suspension test in mice. This study investigated the antidepressant-like effect of the ethanolic extract from aerial part of S. molle in the forced swimming test and tail suspension test in mice, two predictive models of depression. Moreover, we investigated the antidepressant potential of rutin, a flavonoid isolated from the ethanolic extract of this plant and the influence of the pretreatment with the inhibitors of serotonin or noradrenaline synthesis, p-chlorophenylalanine methyl ester (PCPA) and alpha-methyl-p-tyrosine (AMPT), respectively in the antidepressant-like effect of this flavonoid. The administration of the ethanolic extract produced a reduction in the immobility time in the tail suspension test (dose range 600-1000 mg/kg, p.o.), but not in the forced swimming test. It also produced a reduction in the ambulation in the open-field test in mice not previously habituated to the arena, but no effect in the locomotor activity in mice previously habituated to the open-field. The administration of rutin reduced the immobility time in the tail suspension test (0.3-3 mg/kg, p.o.), but not in the forced swimming test, without producing alteration in the locomotor activity. In addition, pretreatment of mice with PCPA (100 mg/kg, i.p., for 4 consecutive days) or AMPT (100 mg/kg, i.p.) prevented the anti-immobility effect of rutin (0.3 mg/kg, p.o.) in the tail suspension test. The results firstly indicated the antidepressant-like effect of the ethanolic extract of S. molle in the tail suspension test may be dependent on the presence of rutin that likely exerts its antidepressant-like effect by increasing the availability of serotonin and noradrenaline in the synaptic cleft.

  10. The Role of MAPK and Dopaminergic Synapse Signaling Pathways in Antidepressant Effect of Electroacupuncture Pretreatment in Chronic Restraint Stress Rats

    Directory of Open Access Journals (Sweden)

    Xinjing Yang

    2017-01-01

    Full Text Available Acupuncture has demonstrated the function in ameliorating depressive-like behaviors via modulating PKA/CREB signaling pathway. To further confirm the antidepressant mechanism of EA on the mitogen-activated protein kinase (MAPK and dopaminergic synapse signaling pathways, 4 target proteins were detected based on our previous iTRAQ analysis. Rats were randomly divided into control group, model group, and electroacupuncture (EA group. Except for the control group, all rats were subjected to 28 days of chronic restraint stress (CRS protocols to induce depression. In the EA group, EA pretreatment at Baihui (GV20 and Yintang (GV29 was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes prior to restraint. The antidepressant-like effect of EA was measured by body weight and open-field test. The protein levels of DAT, Th, Mapt, and Prkc in the hippocampus were examined by using Western blot. The results showed EA could ameliorate the depression-like behaviors and regulate the expression levels of Prkc and Mapt in CRS rats. The effect of EA on DAT and Th expression was minimal. These findings implied that EA pretreatment could alleviate depression through modulating MAPK signaling pathway. The role of EA on dopaminergic synapse signaling pathways needs to be further explored.

  11. Murine depression model and its potential applications for discovering foods and farm products with antidepressant-like effects

    Directory of Open Access Journals (Sweden)

    Tatsuhiko eGoto

    2016-03-01

    Full Text Available Advanced societies face increased health problems related to various stresses. Chronic psychological stress is a major risk factor for psychiatric disorders such as depression. Although therapeutic agents reduce several symptoms of depression, most have side effects in a broad range of the population. Furthermore, some victims of depression do not show significant improvement with any drugs, so alternative approaches are needed. Good dietary habits may potentially reduce depressive symptoms, but there is little scientific evidence thus far. Murine depression models are useful to test nutritional approaches in vivo. Our model mice subjected to a subchronic mild social defeat stress (sCSDS paradigm show several alterations in physiological parameters and social behavior. These stress-induced symptoms in sCSDS mice can be used as cues to identify antidepressant-like natural resources including foods and farm products. We previously discovered that sCSDS mice show more vulnerability to social stress by changing dietary condition. In addition, we developed a more objective system for analyzing mouse behavior using a 3D depth-sensing camera to understand relationships between diet and behavior. The combination of sCSDS mice with 3D behavioral analysis is a powerful method for screening ingredients in foods and farm products for antidepressant-like effects.

  12. The antidepressant-like effect of Mentha spicata essential oil in animal models of depression in male mice

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    Behnam Jedi-Behnia

    2017-06-01

    Full Text Available Background & Objective: Previous researches have revealed analgesic and sedative properties of Mentha spicata (MS. The aim of present study was to evaluate the antidepressant effects of MS essential oil in forced swim test (FST and tail suspension test (TST in male mice. Materials & Methods: In this experimental study, 84 male mice were randomly divided into 14 groups of 6: Negative control groups received normal saline (10 ml/kg,i.p., positive control groups received fluoxetine (20mg/kg, i.p. and imipramine (30mg/kg and treatment groups received MS essential oil (30, 60,120 and 240 mg/kg i.p.. In FST, immobility time, swimming time and climbing time and immobility time in TST were recorded in six minutes. Results: Findings indicated that essential oil at doses of 120 and 240 mg/kg, fluoxetine and imipramine reduced immobility time compared to control group in FST and TST (p0.05. In contrast, imipramine increased climbing time without any significant change in swimming time (p>0.05. Conclusion: Based on the findings of the present study, MS essential oil has antidepressant-like activity similar to fluoxetine and probably their compounds (especially carvone with serotonergic mechanism induced their effect. However, further studies are needed to determine the precise mechanism of its action.

  13. Role of monoaminergic system in the etiology of olive oil induced antidepressant and anxiolytic effects in rats.

    Science.gov (United States)

    Perveen, Tahira; Hashmi, Bilal Moiz; Haider, Saida; Tabassum, Saiqa; Saleem, Sadia; Siddiqui, Munnawar Ahmed

    2013-01-01

    Olive oil is the major component of the Mediterranean diet and has rich history of nutritional and medicinal uses. In the present study, the antidepressant and anxiolytic effects and their neurochemical basis following repeated administration of extravirgin olive oil were monitored. Male albino Wistar rats were used during study. Animals of test group were given olive oil orally at the dose of 0.25 mL/kg daily for 4 weeks. Control rats received equal volume of water. Elevated-plus maze (EPM) test and forced swim test (FST) were performed for the assessment of anxiety and depression like symptoms. An increase in time spent in open arm in EPM and increased struggling time in FST following long-term administration of olive oil indicate that olive oil has anxiolytic and antidepressant properties. Neurochemical results showed that repeated administration of olive oil decreased the levels of brain 5-HT (5-hydroxytryptamine), 5-HIAA (5-hydroxyindoleacetic acid), and levels of DA (dopamine); however, levels of DA metabolite HVA (homovalinic acid) were increased. Hence, present findings suggest that olive oil has neuroprotective effects. It reduces behavioral deficits via altering 5-HT and DA metabolism. So it could be used as a therapeutic substance for the treatment of depression and anxiety.

  14. Involvement of monoaminergic systems in the antidepressant-like effect of Eugenia brasiliensis Lam. (Myrtaceae) in the tail suspension test in mice.

    Science.gov (United States)

    Colla, André R S; Machado, Daniele G; Bettio, Luis E B; Colla, Guilherme; Magina, Michele D A; Brighente, Inês M C; Rodrigues, Ana Lúcia S

    2012-09-28

    Several species of Eugenia L. are used in folk medicine for the treatment of various diseases. Eugenia brasiliensis is used for the treatment of inflammatory diseases, whereas Eugenia. uniflora is used for the treatment of symptoms related to depression and mood disorders, and is used in Brazil by the Guarani Indians as a tonic stimulant. To investigate the antidepressant-like effect of hydroalcoholic extracts of different plant species of genus Eugenia and to characterize the participation of the monoaminergic systems in the mechanism of action of the specie that afforded the most prominent antidepressant-like efficacy. In the first set of experiments, the effects of hydroalcoholic extracts of Eugenia beaurepaireana, Eugenia brasiliensis, Eugenia catharinae, Eugenia umbelliflora and Eugenia uniflora and the antidepressant fluoxetine (positive control) administered acutely by p.o. route were evaluated in the tail suspension test (TST) and locomotor activity was assessed in the open-field test in mice. In the second set of experiments, the involvement of the monoaminergic systems in the antidepressant-like activity of Eugenia brasiliensis was evaluated by treating mice with several pharmacological agonists and antagonists. The effects of the combined administration of sub-effective doses of Eugenia brasiliensis and the antidepressants fluoxetine, imipramine and bupropion were also evaluated. The administration of the extracts from Eugenia brasiliensis, Eugenia catharinae and Eugenia umbelliflora, but not Eugenia beaurepaireana and Eugenia uniflora, exerted a significant antidepressant-like effect, without altering locomotor activity. The behavioral profile was similar to fluoxetine. Pre-treatment of mice with ketanserin, haloperidol, SCH23390, sulpiride, prazosin and yohimbine prevented the reduction of immobility time induced by Eugenia brasiliensis. Treatment with sub-effective doses of WAY100635, SKF38393, apomorphine, phenylephrine, but not clonidine, combined

  15. Antidepressant-like effect of the hydroethanolic leaf extract of Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg. (Euphorbiaceae) in mice: involvement of monoaminergic system.

    Science.gov (United States)

    Ishola, Ismail O; Agbaje, Esther O; Akinleye, Moshood O; Ibeh, Chris O; Adeyemi, Olufunmilayo O

    2014-12-02

    The leaf of Alchornea cordifolia (Euphorbiaceae) is used in traditional African medicine in the treatment of various neurological and psychiatric disorders including depression. Previous studies have shown its potent antidepressant-like effect in the forced swimming test (FST). Hence, this study sought to investigate the involvement of monoaminergic systems in the antidepressant-like effect elicited by hydroethanolic leaf extract of Alchornea cordifolia (HeAC) in the FST. HeAC (25-400mg/kg, p.o.) was administered 1h before the FST. To investigate the contribution of monoaminergic systems to antidepressant-like effect, receptors antagonists were injected 15min before oral administration of HeAC (200mg/kg) to mice and 1h thereafter, subjected to FST. HeAC (200 and 400mg/kg, p.o.) produced dose dependent and significant (P<0.001) antidepressant-like effect, in the FST, without accompanying changes in spontaneous locomotor activities in the open-field test. The anti-immobility effect of HeAC (200mg/kg) in the FST was prevented by pretreatment of mice with SCH 23390 (0.05mg/kg, s.c., a dopamine D1 receptor antagonist), sulpiride (50mg/kg, i.p., a dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., an α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist), and GR 127993 (5-HT1B receptor antagonist). Similarly, 3 days intraperitoneal injection of p-chlorophenylalanine (pCPA, 150mg/kg, i.p., an inhibitor of serotonin synthesis) prevented the antidepressant-like effect elicited by HeAC. The combination of subeffective doses of imipramine (5mg/kg, p.o.) or fluoxetine (5mg/kg, p.o.), with HeAC (25mg/kg, p.o., subeffective dose) produced a synergistic antidepressant-like effect in the FST. The hydroethanolic extract of Alchornea cordifolia possesses antidepressant-like effect mediated through interaction with dopamine (D1 and D2), noradrenergic (α1 and α2 adrenoceptors), and serotonergic (5HT1B receptors) systems. Also, the potentiation

  16. Antidepressants: Safe during Pregnancy?

    Science.gov (United States)

    Healthy Lifestyle Pregnancy week by week Taking antidepressants during pregnancy might pose health risks for your baby — but stopping might ... 2017 Original article: http://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/antidepressants/art-20046420 . ...

  17. Aqueous Extract of Pomegranate Alone or in Combination with Citalopram Produces Antidepressant-Like Effects in an Animal Model of Menopause: Participation of Estrogen Receptors

    Directory of Open Access Journals (Sweden)

    Brenda Valdés-Sustaita

    2017-12-01

    Full Text Available It has been reported that the aqueous extract of pomegranate (AE-PG has polyphenols with estrogenic-like activities. The present work determines if AE-PG alone or in combination with the selective serotonin reuptake inhibitor, citalopram, has antidepressant-like effects. It was also analyzed the participation of estrogen receptors (ER. AE-PG (0.1, 1.0, 10, or 100 mg/kg was evaluated in ovariectomized female Wistar rats subjected to the forced swimming test. The effects induced by AE-PG were compared with those of citalopram (2.5, 5.0, 10, and 20.0 mg/kg and 17β-estradiol (E2; 2.5 5.0, and 10 μg/rat. Likewise, the combination of suboptimal doses of AE-PG (0.1 mg/kg plus citalopram (2.5 mg/kg was evaluated. To determine if ER participates in the antidepressant-like action of pomegranate, the estrogen antagonist tamoxifen (15 mg/kg was administered with AE-PG (1 mg/kg. AE-PG produced antidepressant-like actions with a similar behavioral profile induced by citalopram and E2. Suboptimal doses of citalopram plus AE-PG produced antidepressant-like effects. Tamoxifen was able to block AE-PG’s antidepressant-like actions. These results confirm the participation of ER in AE-PG’s antidepressant-like effects. Furthermore, the additive effects observed with the combined treatment of AE-PG plus citalopram could be advantageous in the treatment of depressive disorders, such as menopause.

  18. Thymol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in mice.

    Science.gov (United States)

    Deng, Xue-Yang; Li, Hong-Yan; Chen, Jun-Jun; Li, Rui-Peng; Qu, Rong; Fu, Qiang; Ma, Shi-Ping

    2015-09-15

    Thymol, a bioactive monoterpene isolated from Thymus vulgaris, has displayed inspiring neuroprotective properties. The present study was designed to evaluate the antidepressant-like effects of thymol on a chronic unpredictable mild stress (CUMS) model of depression in mice and explore the underlying mechanisms. It was observed that thymol treatment (15 mg/kg and 30 mg/kg) significantly reversed the decrease of sucrose consumption, the loss of body weight, the reduction of immobile time in the tail suspension tests (TST) and forced swimming tests (FST) induced by CUMS paradigm. The levels of norepinephrine (NE) and serotonin (5-HT) in the hippocampus decreased in the CUMS-treated mice. Chronic treatments with thymol significantly restored the CUMS-induced alterations of monoamine neurotransmitters in the hippocampus. Our results further demonstrated that thymol administration negatively regulated the induction of proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in CUMS mice. Furthermore, thymol inhibited the activation of nod-like receptor protein 3 (NLRP3) inflammasome and its adaptor, and subsequently decreased the expression of caspase-1. In sum, our findings suggested that thymol played a potential antidepressant role in CUMS mice model through up-regulating the levels of central neurotransmitters and inhibiting the expressions of proinflammatory cytokines, which might provide potential for thymol in the light of opening up new therapeutic avenues for depression. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. The effects of a palliative care program on antidepressant use and continuing maintenance medications in near end-of-life oncology patients (the HEALED study).

    Science.gov (United States)

    Thomas, Hilary; Randolph, Monica; Pruemer, Jane

    2015-10-01

    The use of antidepressants and maintenance medications for cancer patients in a palliative care setting is controversial. The effectiveness of antidepressants and consequences of discontinuing maintenance medications are unknown in this population. Compare the quality of life of patients taking and not taking antidepressants at entry to a palliative care clinic, and to observe maintenance medication use in this population, along with consequences of stopping them. Prospective, monthly review of medications, quality of life, and hospitalizations were recorded from oncology patients that attended a palliative care clinic. In addition, a retrospective chart review of medications and hospitalizations of oncology patients that did and did not attend a palliative care clinic was performed. Forty-three prospective patients were enrolled. Patients had similar quality of life whether or not they were taking antidepressants (p = 0.52). Number of maintenance medications at entry and at final evaluation did not change (p = 0.45). No hospitalizations were caused by discontinuation of maintenance medications. QOL of patients did not decline after coming to the clinic based on the baseline and second FACT-G questionnaires (p = 0.84). Fifty-six patients were included in the retrospective portion of this study. The non-palliative care patients had higher proportions of maintenance medications and rates of hospitalizations when compared to the palliative care patients. Quality of life is essentially the same between palliative care patients, whether they are receiving antidepressants or not. © The Author(s) 2014.

  20. Effect of co-administration of memantine and sertraline on the antidepressant-like activity and brain-derived neurotrophic factor (BDNF) levels in the rat brain.

    Science.gov (United States)

    Amidfar, Meysam; Réus, Gislaine Z; Quevedo, João; Kim, Yong-Ku; Arbabi, Mohammad

    2017-01-01

    A developing body of data has drawn attention to the N-methyl-d-aspartate (NMDA) receptor antagonists as potential drugs for the treatment of major depressive disorder (MDD). We investigated the possibility of synergistic interactions between the antidepressant sertraline with the uncompetitive NMDA receptor antagonist, memantine. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with memantine and sertraline alone or in combination in rats. To this aim, rats were chronically treated with memantine (2.5 and 5mg/kg) and sertraline (5mg/kg) for 14days once a day, and then exposed to the forced swimming test. The brain-derived neurotrophic factor (BDNF) levels were assessed in the hippocampus and prefrontal cortex in all groups by ELISA sandwich assay. Sertraline and memantine (2.5mg/kg) alone did not have effect on the immobility time; however, the effect of sertraline was enhanced by both doses of memantine. Combined treatment with memantine and sertraline produced stronger increases in the BDNF protein levels in the hippocampus and prefrontal cortex. Our results indicate that co-administration of antidepressant memantine with sertraline may induce a more pronounced antidepressant activity than treatment with each antidepressant alone. Antidepressant properties using the combination of memantine and sertraline could be attributed to increased levels of BDNF. This finding may be of particular importance in the case of drug-resistant patients and could suggest a method of obtaining significant antidepressant actions whereas limiting side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

    DEFF Research Database (Denmark)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders

    2010-01-01

    symptom of depression, was assessed by measuring consumption of a palatable solution. Exposure to CUS reduced intake of a palatable solution and this effect was prevented by chronic antidepressant treatment. Moreover, chronic antidepressant treatment decreased depressive-like behavior in a modified forced...... mRNA expression in both the dentate gyrus of the dorsal hippocampus and the CA3 region of the ventral hippocampus indicating that there is no simple link between depression-like behaviors per se and brain BDNF levels in rats. However, a significant increase in BDNF mRNA levels in the dentate gyrus...

  2. Latent change score modeling as a method for analyzing the antidepressant effect of a psychosocial intervention in Alzheimer's disease.

    Science.gov (United States)

    Werheid, Katja; Köhncke, Ylva; Ziegler, Matthias; Kurz, Alexander

    2015-01-01

    Developing and evaluating interventions for patients with age-associated disorders is a rising field in psychotherapy research. Its methodological challenges include the high between-subject variability and the wealth of influencing factors associated with longer lifetime. Latent change score modeling (LCSM), a technique based on structural equation modeling, may be well suited to analyzing longitudinal data sets obtained in clinical trials. Here, we used LCSM to evaluate the antidepressant effect of a combined cognitive behavioral/cognitive rehabilitation (CB/CR) intervention in Alzheimer's disease (AD). LCSM was applied to predict the change in depressive symptoms from baseline as an outcome of the CORDIAL study, a randomized controlled trial involving 201 patients with mild AD. The participants underwent either the CORDIAL CB/CR program or standard treatment. Using LCSM, the model best predicting changes in Geriatric Depression Scale scores was determined based on this data set. The best fit was achieved by a model predicting a decline in depressive symptoms between before and after testing. Assignment to the intervention group as well as female gender revealed significant effects in model fit indices, which remained stable at 6- and 12-month follow-up examinations. The pre-post effect was pronounced for patients with clinically relevant depressive symptoms at baseline. LCSM confirmed the antidepressant effect of the CORDIAL therapy program, which was limited to women. The effect was pronounced in patients with clinically relevant depressive symptoms at baseline. Methodologically, LCSM appears well suited to analyzing longitudinal data from clinical trials in aged populations, by accounting for the high between-subject variability and providing information on the differential indication of the probed intervention.

  3. Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test.

    Science.gov (United States)

    Nazari, Seyedeh Khadijeh; Nikoui, Vahid; Ostadhadi, Sattar; Chegini, Zahra Hadi; Oryan, Shahrbanoo; Bakhtiarian, Azam

    2016-12-01

    Previous study confirmed that the acute treatment with baclofen by inhibition of the l-arginine-nitric oxide (NO) pathway diminished the immobility behavior in the forced swimming test (FST) of mice. Considering the involvement of NO in adenosine triphosphate (ATP)-sensitive potassium channels (KATP), in the present study we investigated the involvement of KATP channels in antidepressant-like effect of baclofen in the forced swimming test (FST). After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of the antidepressant-like activity of baclofen in mice. Baclofen at different doses (0.1, 0.3, and 1mg/kg) and fluoxetine (20mg/kg) were administrated by intraperitoneal (ip) route, 30min before the FST or OFT. To clarify the probable involvement of KATP channels, after determination of sub-effective doses of glibenclamide as a KATP channel blocker and cromakalim, as an opener of these channels, they were co-administrated with the sub-effective and effective doses of baclofen, respectively. Baclofen at dose 1mg/kg significantly decreased the immobility behavior of mice similar to fluoxetine (20mg/kg). Co-administration of gelibenclamide sub-effective dose (1mg/kg) with baclofen (0.1mg/kg) showed a synergistic antidepressant-like effect in the FST. Also, sub-effective dose of cromakalim (0.1mg/kg) inhibited the antidepressant-like effect of baclofen (1mg/kg) in the FST. All aforementioned treatments had not any impact on the locomotor movement of mice in OFT. Our study for the first time revealed that antidepressant-like effect of baclofen on mice is KATP-dependent, and baclofen seems that exert this effect by blocking the KATP channels. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  4. VGF function in depression and antidepressant efficacy.

    Science.gov (United States)

    Jiang, C; Lin, W-J; Sadahiro, M; Labonté, B; Menard, C; Pfau, M L; Tamminga, C A; Turecki, G; Nestler, E J; Russo, S J; Salton, S R

    2017-11-21

    Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes. Mice with reduced VGF levels in the germ line (Vgf+/-) or in dHc (AAV-Cre-injected floxed mice) showed increased susceptibility to CSDS and impaired responses to ketamine treatment in the forced swim test. Floxed mice with conditional pan-neuronal (Synapsin-Cre) but not those with forebrain (αCaMKII-Cre) Vgf ablation displayed increased susceptibility to subthreshold social defeat stress, suggesting that neuronal VGF, expressed in part in inhibitory interneurons, regulates depression-like behavior. Acute antibody-mediated sequestration of VGF-derived C-terminal peptides AQEE-30 and TLQP-62 in dHc induced pro-depressant effects. Conversely, dHc TLQP-62 infusion had rapid antidepressant efficacy, which was reduced in BDNF floxed mice injected in dHc with AAV-Cre, and in NBQX- and rapamycin-pretreated wild-type mice, these compounds blocking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling, respectively. VGF is therefore a critical modulator of depression-like behaviors in dHc and NAc. In hippocampus, the antidepressant response to ketamine is associated with rapid VGF translation, is impaired by reduced VGF expression, and as previously reported, requires coincident, rapid BDNF translation and release.Molecular Psychiatry advance online publication, 21 November

  5. Antidepressants and dementia

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Søndergaard, Lars; Forman, Julie Lyng

    2009-01-01

    BACKGROUND: It has been suggested that antidepressants may have neuroprotective abilities but it has newer been investigated lately whether treatment with antidepressants reduces the risk of dementia. METHOD: Linkage of registers of all prescribed antidepressants and diagnoses of dementia...... in Denmark during a period from 1995 to 2005. RESULTS: Persons who purchased antidepressants once (N=687,552) had an increased rate of dementia compared to persons unexposed to antidepressants (N=779,831). Nevertheless, the rate of dementia changed over time; thus during the initial prescription periods...... the rate increased with the number of prescriptions but continued long-term antidepressants treatment was associated with a reduction in the rate of dementia, however, not to the same level as the rate for the general population. This pattern was found for all classes of antidepressants (SSRIs, newer non...

  6. Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Olsen, G M; Wiborg, O

    2009-01-01

    AChR subtype/s involved remains unknown. In this study, we systematically compared the effects of non-selective and selective nicotinic agonists and antagonists in two different tests for antidepressant effects in mice: the tail suspension test and the forced swim test. Compounds: nicotine, RJR-2403 (alpha4...... compounds were tested in a locomotor activity paradigm to rule out non-specific stimulant effects. The data show that blockade of nAChRs with mecamylamine, or selective antagonism of alpha4beta2 or alpha7 nAChRs with DHbetaE or MLA, respectively, has antidepressant-like effects. These effects were...... not confounded by motor stimulation. Hexamethonium did not show antidepressant-like activity, supporting the involvement of central nAChRs. At the dose levels tested, none of the nAChR agonists displayed antidepressant-like profiles. In conclusion, antagonism of central alpha4beta2 and/or alpha7 nAChRs induced...

  7. Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

    Directory of Open Access Journals (Sweden)

    Cecilia Csölle

    Full Text Available Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7 results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/- displayed decreased immobility in the tail suspension test (TST and an attenuated anhedonia response in the sucrose preference test (SPT following bacterial endotoxin (LPS challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [(3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5. An increased 5-bromo-2-deoxyuridine (BrdU incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [(3H]5-HT and an elevated number of [(3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus.

  8. The effects of anti-depressants on depression symptom scores at 12 months follow-up in patients with cardiometabolic disease: Results from a large primary care cohort

    Directory of Open Access Journals (Sweden)

    Bhautesh Dinesh Jani

    2015-01-01

    Full Text Available Background: Evidence on the long-term usefulness of anti-depressants in managing depression in cardiometabolic disease is limited. Aim: We examined the effects of anti-depressant prescribing on depressive symptoms at 12 months follow-up in patients with cardiometabolic disease and a positive depression screening result at baseline. Design and Setting: We retrospectively reviewed routine UK primary care data for patients with coronary heart disease, diabetes and previous stroke for the year 2008-2009. 35,537 patients with one of the three above diseases underwent depression screening using the Hospital Anxiety and Depression Scale (HADS-D. Of 7080 patients with a positive screening result (HADS-D ≥ 8, 3933 (55.5% patients had a repeat HADS-D recorded at 12 months follow-up. Methods: We compared the change in HADS-D at follow-up and remission rate in those who were prescribed anti-depressants (n = 223 against those who were not (n = 3710. Results: The mean change in HADS-D from baseline, for the nonprescribed group was similar to the reduction observed in patients who were continuously prescribed (n = 93 with anti-depressants during follow-up. Patients who were prescribed intermittently (n = 72 or only one (n = 58 prescription during follow-up had a lower reduction in HADS-D compared to the nonprescribed group. There was no difference in remission rates between continuously prescribed and the nonprescribed group, but remission was lower in patients prescribed intermittently and single prescription. Conclusion: Improvement in depressive symptoms in patients with cardiometabolic disease at 12 months was not any better in patients prescribed with anti-depressants compared to the nonprescribed group. The role of anti-depressants in the management of depression in cardiometabolic disease merits further investigation.

  9. Reduced vasopressin receptors activation mediates the anti-depressant effects of fluoxetine and venlafaxine in bulbectomy model of depression.

    Science.gov (United States)

    Poretti, María Belén; Sawant, Rahul S; Rask-Andersen, Mathias; de Cuneo, Marta Fiol; Schiöth, Helgi B; Perez, Mariela F; Carlini, Valeria Paola

    2016-03-01

    In response to stress, corticotropin releasing hormone (CRH) and vasopressin (AVP) are released from the hypothalamus, activate their receptors (CRHR1, CRHR2 or AVPr1b), and synergistically act to induce adrenocorticotropic hormone (ACTH) release from the anterior pituitary. Overstimulation of this system has been frequently associated with major depression states. The objective of the study is to assess the role of AVP and CRH receptors in fluoxetine and venlafaxine effects on the expression of depression-related behavior. In an animal model of depression (olfactory bulbectomy in mice, OB), we evaluated the effects of fluoxetine or venlafaxine (both 10 mg/kg/day) chronic administration on depression-related behavior in the tail suspension test. Plasma levels of AVP, CRH, and ACTH were determined as well as participation of their receptors in the expression of depression related-behavior and gene expression of AVP and CRH receptors (AVPr1b, CRHR1, and CRHR2) in the pituitary gland. The expression of depressive-like behavior in OB animals was reversed by treatment with both antidepressants. Surprisingly, OB-saline mice exhibited increased AVP and ACTH plasma levels, with no alterations in CRH levels when compared to sham mice. Chronic fluoxetine or venlafaxine reversed these effects. In addition, a significant increase only in AVPr1b gene expression was found in OB-saline. The antidepressant therapy used seems to be more likely related to a reduced activation of AVP rather than CRH receptors, since a positive correlation between AVP levels and depressive-like behavior was observed in OB animals. Furthermore, a full restoration of depressive behavior was observed in OB-fluoxetine- or venlafaxine-treated mice only when AVP was centrally administered but not CRH.

  10. Comparative Effectiveness of Antidepressant Medication versus Psychological Intervention on Depression Symptoms in Women with Infertility and Sexual Dysfunction.

    Science.gov (United States)

    Pasha, Hajar; Basirat, Zahra; Faramarzi, Mahbobeh; Kheirkhah, Farzan

    2018-04-01

    Fertility loss is considered as a challenging experience. This study was conducted to compare the effectiveness of antidepressant medication and psychological intervention on depression symptoms in women with infertility and sexual dysfunctions (SD). This randomized, controlled clinical trial study was completed from December 2014 to June 2015 in Babol, Iran. Of the 485 participants, 93 were randomly assigned in a 1:1:1 ratio to psychosexual therapy (PST), bupropion extended-release (BUP ER) at a dose of 150 mg/d, and control (no intervention) groups. The beck depression inventory (BDI) was completed at the beginning and end of the study. Duration of study was eight weeks. Statistical analyses were performed by using paired-test and analysis of covariance. The mean depression score on the BDI was 22.35 ± 8.70 in all participants. Mean BDI score decreased significantly in both treatment groups (PST: Pinfertility and SD (Registration number: IRCT2015042721955N2).

  11. Clinical application of antidepressants in the treatment of insomnia symptoms

    Directory of Open Access Journals (Sweden)

    WONG Iok-man

    2013-11-01

    Full Text Available Insomnia is one of the common complaints among all clinical departments. In recent years, some studies have demonstrated that insomnia symptoms can be improved or treated by some antidepressants. Based on literature search both at home and abroad, this paper summarized the effect of various antidepressants with different pharmacological properties on sleep, and the progress of clinical application of antidepressants in treating insomnia according to the classification of antidepressant drugs.

  12. Deep brain stimulation in rats: different targets induce similar antidepressant-like effects but influence different circuits.

    Science.gov (United States)

    Hamani, Clement; Amorim, Beatriz O; Wheeler, Anne L; Diwan, Mustansir; Driesslein, Klaus; Covolan, Luciene; Butson, Christopher R; Nobrega, José N

    2014-11-01

    Recent studies in patients with treatment-resistant depression have shown similar results with the use of deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG), ventral capsule/ventral striatum (VC/VS) and nucleus accumbens (Acb). As these brain regions are interconnected, one hypothesis is that by stimulating these targets one would just be influencing different relays in the same circuitry. We investigate behavioral, immediate early gene expression, and functional connectivity changes in rats given DBS in homologous regions, namely the ventromedial prefrontal cortex (vmPFC), white matter fibers of the frontal region (WMF) and nucleus accumbens. We found that DBS delivered to the vmPFC, Acb but not WMF induced significant antidepressant-like effects in the FST (31%, 44%, and 17% reduction in immobility compared to controls). Despite these findings, stimulation applied to these three targets induced distinct patterns of regional activity and functional connectivity. While animals given vmPFC DBS had increased cortical zif268 expression, changes after Acb stimulation were primarily observed in subcortical structures. In animals receiving WMF DBS, both cortical and subcortical structures at a distance from the target were influenced by stimulation. In regard to functional connectivity, DBS in all targets decreased intercorrelations among cortical areas. This is in contrast to the clear differences observed in subcortical connectivity, which was reduced after vmPFC DBS but increased in rats receiving Acb or WMF stimulation. In conclusion, results from our study suggest that, despite similar antidepressant-like effects, stimulation of the vmPFC, WMF and Acb induces distinct changes in regional brain activity and functional connectivity. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Antidepressants in the treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Sindrup, Søren H.; Otto, Marit; Finnerup, Nanna Brix

    2005-01-01

    presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated......Neuropathic pain is due to lesion or dysfunction of the peripheral or central nervous system. Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit...... in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2-3 patients with peripheral...

  14. Appearance of antidepressant-like effect by sildenafil in rats after central muscarinic receptor blockade: evidence from behavioural and neuro-receptor studies.

    Science.gov (United States)

    Brink, C B; Clapton, J D; Eagar, B E; Harvey, B H

    2008-01-01

    The phosphodiesterase (PDE) 5 inhibitor sildenafil has been shown to display psychotropic actions in humans and animals, and has been used for the treatment of antidepressant-associated erectile dysfunction. However, its effects on the neurobiology of depression are unknown. Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) inhibition is anti-depressant in animals, and increasing cGMP with sildenafil is anxiogenic in rodents. Substantial cholinergic-nitrergic interaction exists in the brain, while sildenafil shows modulatory actions on cholinergic transmission. Depression is also associated with increased cholinergic drive. Here we report that sildenafil increases muscarinic acetylcholine receptor (mAChR) signaling in human neuroblastoma cells. We also show that fluoxetine (20 mg/kg/day x 7 days), as well as a combination of sildenafil (10 mg/kg/day x 7 days) plus the antimuscarinic atropine (1 mg/kg/day x 7 days) demonstrates significant, comparable antidepressant-like effects in the rat forced swim test (FST) and also reduces cortical beta-adrenergic receptor (beta-AR) density, while sildenafil or atropine alone did not. Importantly, sildenafil did not modify fluoxetine's response. Sildenafil thus demonstrates antidepressant-like effects but only after central muscarinic receptor blockade, providing evidence for cholinergic-nitrergic interactions in the neurobiology of depression.

  15. [Metabolic safety of antidepressant medicines].

    Science.gov (United States)

    Łężak, Wojciech; Mokros, Łukasz; Karbownik, Michał Seweryn; Witusik, Andrzej; Kosmalski, Marcin; Kowalczyk, Edward; Pietras, Tadeusz

    2017-05-23

    Metabolic syndrome is a very serious health issue, not only from internal medicine's point of view. Patients suffering from overweight, arterial hypertension, lipids and carbohydrates metabolism disorders are also in the circle of interest of other areas of medicine, including psychiatry. Currently, one of key problems of pharmacotherapy is a comorbidity of metabolic syndrome and mental disorder. Depression is more common than schizophrenia. Despite the fact that in everyday clinical practice there are more patients with depression than schizophrenia, there is a bigger interest among scientists for metabolic syndrome after antipsychotic drugs than as an effect of use of antidepressant agents. The aim of an analysis was to review literature committed to influence of depression pharmacotherapy on development of metabolic syndrome. 169 results were provided, including 18 original publications. Final analysis consists of 9 that investigate correlation between antidepressive medicines use and metabolic syndrome development (but not its each individual component). In general, antidepressant pharmacotherapy is associated not only with increased risk of metabolic syndrome occurrence but also their worsening. However, it needs to be emphasized that there is a difference between antidepressants groups - tricyclic antidepressive medicines are the most commonly associated with risk of developing metabolic disorders, but also SNRIs and SSRIs are mentioned as significant contributors. Mechanisms of aforementioned changes are still unclear. However, their influence on histamine and serotonin pathways, which take part in regulation of i.e. food intake, is suggested. The search for mechanisms that are precisely responsible for metabolic changes continues, in hope of finding a way to avoid adverse effects of antidepressant medicines use.

  16. Evidence for the involvement of the serotonergic 5-HT(1A) receptors in the antidepressant-like effect caused by hesperidin in mice.

    Science.gov (United States)

    Souza, Leandro C; de Gomes, Marcelo G; Goes, André T R; Del Fabbro, Lucian; Filho, Carlos B; Boeira, Silvana P; Jesse, Cristiano R

    2013-01-10

    The present study investigated a possible antidepressant-like activity of hesperidin using two predictive tests for antidepressant effect in mice: the forced swimming test (FST) and the tail suspension test (TST). Results demonstrated that hesperidin (0.1, 0.3 and 1 mg/kg, intraperitoneal, i.p.) decreased the immobility time in the FST and TST without affecting the locomotor activity in the open field test. The antidepressant-like effect of hesperidin (0.3 mg/kg) on the TST was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (pCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis) and WAY100635 (0.1 mg/kg, subcutaneous, s.c., a selective 5-HT(1A) receptor antagonist). Pretreatment of mice with prazosin (1 mg/kg, i.p., an α(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α(2)-adrenoceptor antagonist), propranolol (2 mg/kg, i.p., a β-adrenoceptor antagonist), AMPT (100 mg/kg, i.p., an inhibitor of tyrosine hydroxylase), SCH23390 (0.05 mg/kg, s.c., a dopamine D(1) receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D(2) receptor antagonist), ketanserin (1mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist) or MDL72222 (1 mg/kg, i.p., a 5-HT(3) receptor antagonist) did not block the antidepressant-like effect of hesperidin (0.3 mg/kg, i.p.) in the TST. Administration of hesperidin (0.01 mg/kg, i.p.) and fluoxetine (1 mg/kg), at subeffective doses, produced an antidepressant-like effect in the TST. The antidepressant-like effect caused by hesperidin in mice in the TST was dependent on an interaction with the serotonergic 5-HT(1A) receptors. Taken together, these results suggest that hesperidin possesses antidepressant-like property and may be of interest source for therapeutic agent for the treatment of depressive disorders. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  17. Involvement of norepinephrine and serotonin system in antidepressant-like effects of oleoylethanolamide in the mice models of behavior despair.

    Science.gov (United States)

    Yu, Hai-Ling; Sun, Lian-Ping; Li, Miao-Miao; Quan, Zhe-Shan

    2015-04-23

    Oleoylethanolamide (OEA) is an endocannabinoid analogy that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In the present study, we investigated the antidepressant- like potential of OEA in mice in comparison with clomipramine (Cp). 50 mice were randomly divided into 5 groups, and treated with a vehicle (0.3% methyl cellulose, 20 mL/kg, p.o.), OEA (2.5, 5-10mg/kg, p.o.), or Cp (10mg/kg, p.o.) for 7 days. The immobility was used to evaluate depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST). ELISA detected changes in cerebral noradrenaline (NE) and serotonin (5-HT) levels. Likewise, in the drug-induced model of depression, OEA was given once daily at 10mg/kg (p.o.) for 7 consecutive days. Then, the mice received reserpine (4 mg/kg, i.p.) and the rectal temperature was measured at different time points. Consequently, head twitch behavior induced by intraperitoneal injection of 5-hydroxy-tryptophan (5-HTP; 300 mg/kg) were determined. The experimental data showed that OEA (2.5-10mg/kg) treatment significantly decreased the immobility as compared to the control group, and OEA (10mg/kg) treatment significantly increased 5-HTP-induced head twitch behavior and reversed reserpine-induced hypothermia and increased cerebral levels of NE and 5-HT. Thus, the antidepressant effects of OEA may be related to regulating central monoamine neurotransmitters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. The antidepressant-like effect of Ocimum basilicum in an animal model of depression.

    Science.gov (United States)

    Ali, S S; Abd El Wahab, M G; Ayuob, N N; Suliaman, M

    2017-01-01

    We investigated the efficacy of Ocimum basilicum (OB) essential oils for treating depression related behavioral, biochemical and histopathological changes caused by exposure to chronic unpredictable mild stress (CUMS) in mice and to explore the mechanism underlying the pathology. Male albino mice were divided into four groups: controls; CUMS; CUMS plus fluoxetine, the antidepressant administered for pharmacological validation of OB; and CUMS plus OB. Behavioral tests included the forced swim test (FST), elevated plus-maze (EPM) and the open field test (OFT); these tests were performed at the end of the experiment. We assessed serum corticosterone level, protein, gene and immunoexpression of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) as well as immunoexpression of glial fibrillary acidic protein (GFAP), Ki67, caspase-3 in the hippocampus. CUMS caused depression in the mice as evidenced by prolonged immobility in the FST, prolonged time spent in the open arms during the EPM test and reduction of open field activity in the OFT. OB ameliorated the CUMS induced depressive status. OB significantly reduced the corticosterone level and up-regulated protein and gene expressions of BDNF and GR. OB reduced CUMS induced hippocampal neuron atrophy and apoptosis, and increased the number of the astrocytes and new nerve cells. OB significantly increased GFAP-positive cells as well as BDNF and GR immunoexpression in the hippocampus.

  19. A synthetic bioisoster of trimethadione and phenytoin elicits anticonvulsant effect, protects the brain oxidative damage produced by seizures and exerts antidepressant action in mice.

    Science.gov (United States)

    Pastore, Valentina; Wasowski, Cristina; Higgs, Josefina; Mangialavori, Irene C; Bruno-Blanch, Luis E; Marder, Mariel

    2014-08-01

    Epilepsy is recognized as one of the most common and serious neurological disorder affecting 1-2% of the world׳s population. The present study demonstrates that systemic administration of 3-butyl-5,5-dimethyl-1,2,3-oxathiazolidine-4-one-2,2-dioxide (DIOXIDE), a synthetic compound bioisoster of trimethadione and phenytoin (classical anticonvulsants), elicits a dose dependent anticonvulsant response in mice submitted to the subcutaneous pentylenetetrazole seizure test (scPTZ). Among various factors supposed to play role in epilepsy, oxidative stress and reactive species have strongly emerged. The protection exerted by DIOXIDE over the extent of brain oxidative damage produced by PTZ was determined, by measuring the levels of lipid peroxidation and reduced glutathione and the activity of Na(+)/K(+)-ATPase. Psychiatric disorders represent frequent comorbidities in persons with epilepsy. In this report, the potential anxiolytic and antidepressant activities of DIOXIDE were evaluated in several widely used models for assessing anxiolytic and antidepressant activities in rodents. Although DIOXIDE did not evidence anxiolytic activity at the doses tested, it revealed a significant antidepressant-like effect. Preliminary studies of its mechanism of action, by means of its capacity to act via the GABAA receptor (using the [(3)H]flunitrazepam binding assay in vitro and the picrotoxin test in vivo) and the Na(+) channel (using the alkaloid veratrine, a voltage-Na(+) channel agonist) demonstrated that the anticonvulsant effect is not likely related to the GABAergic pathway and the antidepressant-like effect could be due to its Na(+) channel blocking properties. The results for DIOXIDE suggested it as a new anticonvulsant-antioxidant and antidepressant compound that deserves further development. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  20. The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors.

    Science.gov (United States)

    Wang, Rui; Xu, Ying; Wu, Hong-Li; Li, Ying-Bo; Li, Yu-Hua; Guo, Jia-Bin; Li, Xue-Jun

    2008-01-06

    Curcuma longa is a main constituent of many traditional Chinese medicines, such as Xiaoyao-san, used to manage mental disorders effectively. Curcumin is a major active component of C. longa and its antidepressant-like effect has been previously demonstrated in the forced swimming test. The purpose of this study was to explore the possible contribution of serotonin (5-HT) receptors in the behavioral effects induced by curcumin in this animal model of depression. 5-HT was depleted by the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA, 100 mg/kg, i.p.) prior to the administration of curcumin, and the consequent results showed that PCPA blocked the anti-immobility effect of curcumin in forced swimming test, suggesting the involvement of the serotonergic system. Moreover, pre-treatment of pindolol (10 mg/kg, i.p., a beta-adrenoceptors blocker/5-HT(1A/1B) receptor antagonist), 4-(2'-methoxy-phenyl)-1-[2'-(n-2''-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI, 1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (isamoltane, 2.5 mg/kg, i.p., a 5-HT(1B) receptor antagonist) was found to prevent the effect of curcumin (10 mg/kg) in forced swimming test. On the other hand, a sub-effective dose of curcumin (2.5 mg/kg, p.o.) produced a synergistic effect when given jointly with (+)-8-hydroxy-2-(di-n-propylamino)tetralin, (8-OH-DPAT, 1 mg/kg, i.p., a 5-HT(1A) receptor agonist), anpirtoline (0.25 mg/kg, i.p., a 5-HT(1B) receptor agonist) or ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), but not with ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist with higher affinity to 5-HT(2A) receptor) or R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg, i.p., a 5-HT(2A) receptor agonist). Taken together, these results indicate that the antidepressant-like effect of curcumin in the forced swimming test is related to serotonergic system and may be mediated by, at least

  1. Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter--a review of current understanding of its mechanism of action.

    Science.gov (United States)

    Zhong, Huailing; Haddjeri, Nasser; Sánchez, Connie

    2012-01-01

    Escitalopram is a widely used antidepressant for the treatment of patients with major depression. It is the pure S-enantiomer of racemic citalopram. Several clinical trials and meta-analyses indicate that escitalopram is quantitatively more efficacious than many other antidepressants with a faster onset of action. This paper reviews current knowledge about the mechanism of action of escitalopram. The primary target for escitalopram is the serotonin transporter (SERT), which is responsible for serotonin (or 5-hydroxytryptamine [5-HT]) reuptake at the terminals and cell bodies of serotonergic neurons. Escitalopram and selective serotonin reuptake inhibitors bind with high affinity to the 5-HT binding site (orthosteric site) on the transporter. This leads to antidepressant effects by increasing extracellular 5-HT levels which enhance 5-HT neurotransmission. SERT also has one or more allosteric sites, binding to which modulates activity at the orthosteric binding site but does not directly affect 5-HT reuptake by the transporter. In vitro studies have shown that through allosteric binding, escitalopram decreases its own dissociation rate from the orthosteric site on the SERT. R-citalopram, the nontherapeutic enantiomer in citalopram, is also an allosteric modulator of SERT but can inhibit the actions of escitalopram by interfering negatively with its binding. Both nonclinical studies and some clinical investigations have demonstrated the cellular, neurochemical, neuroadaptive, and neuroplastic changes induced by escitalopram with acute and chronic administration. The findings from binding, neurochemical, and neurophysiological studies may provide a mechanistic rationale for the clinical difference observed with escitalopram compared to other antidepressant therapies.

  2. Agomelatine: an antidepressant with new potent hepatoprotective effects on paracetamol-induced liver damage in rats.

    Science.gov (United States)

    Karakus, E; Halici, Z; Albayrak, A; Polat, B; Bayir, Y; Kiki, I; Cadirci, E; Topcu, A; Aksak, S

    2013-08-01

    Paracetamol was shown to induce hepatotoxicity or more severe fatal acute hepatic damage. Agomelatine, commonly known as melatonin receptor agonist, is a new antidepressant, which resynchronizes circadian rhythms with subjective and objective improvements in sleep quality and architecture, as melatonin does. In the present study, it was aimed to evaluate the hepatoprotective activity of agomelatine on paracetamol-induced hepatotoxicity and to understand the relationship between the hepatoprotective mechanism of agomelatine and antioxidant system and proinflammatory cytokines. A total of 42 rats were divided into 7 groups as each composed of 6 rats: (1) intact, (2) 40 mg/kg agomelatine, (3) 140 mg/kg N-acetylcysteine (NAC), (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 20 mg/kg agomelatine, and (7) 2 g/kg paracetamol + 40 mg/kg agomelatine groups. Paracetamol-induced hepatotoxicity was applied and liver and blood samples were analyzed histopathologically and biochemically. There were statistically significant increases in the activities of aspartate aminotransferase, alanine aminotransferase, levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and 8-iso-prostane, and decreases in the activity of superoxide dismutase and level of glutathione in the group treated with paracetamol. Administration of agomelatine and NAC separately reversed these changes significantly. In conclusion, agomelatine administration protects liver cells from paracetamol-induced hepatotoxicity via antioxidant activity and reduced proinflammatory cytokines, such as TNF-α and IL-6.

  3. Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice

    DEFF Research Database (Denmark)

    Refsgaard, Louise Konradsen; Pickering, Darryl S; Andreasen T., Jesper

    2017-01-01

    Evidence suggests that N-methyl-D-aspartate receptor (NMDAR) antagonists could be efficacious in treating depression and anxiety, but side effects constitute a challenge. This study evaluated the antidepressant-like and anxiolytic-like actions, and cognitive and motor side effects of four NMDAR...... antagonists. MK-801, ketamine, S-ketamine, RO 25-6981 and the positive control, citalopram, were tested for antidepressant-like and anxiolytic-like effects in mice using the forced-swim test, the elevated zero maze and the novelty-induced hypophagia test. Side effects were assessed using a locomotor activity...... test, the modified Y-maze and the rotarod test. All compounds increased swim distance in the forced-swim test. In the elevated zero maze, the GluN2B subtype-selective RO 25-6981 affected none of the measured parameters, whereas all other compounds showed anxiolytic-like effects. In the novelty...

  4. Tricyclic Antidepressants and Tetracyclic Antidepressants

    Science.gov (United States)

    ... Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects. http://www.uptodate.com/home. Accessed June 7, 2016. Mental health medication. National Institute of Mental Health. http://www. ...

  5. [Antidepressants in the elderly].

    Science.gov (United States)

    Cortajarena García, M C; Ron Martin, S; Miranda Vicario, E; Ruiz de Vergara Eguino, A; Azpiazu Gomez, P J; Lopez Aldana, J

    2016-10-01

    Depression in the elderly is a changing, difficult and common disorder. At this age, there are more relapses and more long-life treatment is required. The pharmacology approach is a challenge because of concurrent factors that make their treatment more difficult. It is very important to have a basic antidepressant scheme, in order to help treat this disorder with efficiency and success from Primary Care. There are no drugs without side effects, and their characteristics have to be known in order to make the right selection depending on effectiveness, safety and tolerance. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice.

    Science.gov (United States)

    Jia, Lin; Shang, Yuan-Yuan; Li, Yu-Yuan

    2008-07-21

    To investigate the effects of mirtazapine and fluoxetine, representatives of the noradrenergic and specific serotonergic antidepressant (NaSSA) and selective serotonin reuptake inhibitor (SSRI) antidepressant respectively, on body weight, ingestive behavior, locomotor activity and tumor growth of human pancreatic carcinoma xenografts in nude mice. A subcutaneous xenograft model of human pancreatic cancer cell line SW1990 was established in nude mice. The tumor-bearing mice were randomly divided into mirtazapine group (10 mg/kg per day), fluoxetine group (10 mg/kg per day) and control group (an equivalent normal saline solution) (7 mice in each group). Doses of all drugs were administered orally, once a day for 42 d. Tumor volume and body weight were measured biweekly. Food intake was recorded once a week. Locomotor activity was detected weekly using an open field test (OFT). Compared to the fluoxetine, mirtazapine significantly increased food intake from d 14 to 42 and attenuated the rate of weight loss from d 28 to 42 (t = 4.38, P < 0.05). Compared to the control group, food intake was significantly suppressed from d 21 to 42 and weight loss was promoted from d 35 to 42 in the fluoxetine group (t = 2.52, P < 0.05). There was a significant difference in body weight of the mice after removal of tumors among the three groups. The body weight of mice was the heaviest (13.66 +/- 1.55 g) in the mirtazapine group and the lightest (11.39 +/- 1.45 g) in the fluoxetine group (F( (2,12) ) = 11.43, P < 0.01). The behavioral test on d 7 showed that the horizontal and vertical activities were significantly increased in the mirtazapine group compared with the fluoxetine and control groups (F( (2,18) ) = 10.89, P < 0.01). These effects disappeared in the mirtazapine and fluoxetine groups during 2-6 wk. The grooming activity was higher in the mirtazapine group than in the fluoxetine group (10.1 +/- 2.1 vs 7.1 +/- 1.9 ) (t = 2.40, P < 0.05) in the second week. There was no

  7. Differing antidepressant maintenance methodologies.

    Science.gov (United States)

    Safer, Daniel J

    2017-10-01

    The principle evidence that antidepressant medication (ADM) is an effective maintenance treatment for adults with major depressive disorder (MDD) is from placebo substitution trials. These trials enter responders from ADM efficacy trials into randomized, double-blind placebo-controlled (RDBPC) effectiveness trials to measure the rate of MDD relapse over time. However, other randomized maintenance trial methodologies merit consideration and comparison. A systematic review of ADM randomized maintenance trials included research reports from multiple databases. Relapse rate was the main effectiveness outcome assessed. Five ADM randomized maintenance methodologies for MDD responders are described and compared for outcome. These effectiveness trials include: placebo-substitution, ADM/placebo extension, ADM extension, ADM vs. psychotherapy, and treatment as usual. The placebo-substitution trials for those abruptly switched to placebo resulted in unusually high (46%) rates of relapse over 6-12months, twice the continuing ADM rate. These trials were characterized by selective screening, high attrition, an anxious anticipation of a switch to placebo, and a risk of drug withdrawal symptoms. Selectively screened ADM efficacy responders who entered into 4-12month extension trials experienced relapse rates averaging ~10% with a low attrition rate. Non-industry sponsored randomized trials of adults with multiple prior MDD episodes who were treated with ADM maintenance for 1-2years experienced relapse rates averaging 40%. Placebo substitution trial methodology represents only one approach to assess ADM maintenance. Antidepressant maintenance research for adults with MDD should be evaluated for industry sponsorship, attrition, the impact of the switch to placebo, and major relapse differences in MDD subpopulations. Copyright © 2017. Published by Elsevier Inc.

  8. Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A₁ and A2A receptor activation.

    Science.gov (United States)

    Cunha, Mauricio P; Pazini, Francis L; Rosa, Julia M; Ramos-Hryb, Ana B; Oliveira, Ágatha; Kaster, Manuella P; Rodrigues, Ana Lúcia S

    2015-06-01

    The benefits of creatine supplementation have been reported in a broad range of central nervous systems diseases, including depression. A previous study from our group demonstrated that creatine produces an antidepressant-like effect in the tail suspension test (TST), a predictive model of antidepressant activity. Since depression is associated with a dysfunction of the adenosinergic system, we investigated the involvement of adenosine A1 and A2A receptors in the antidepressant-like effect of creatine in the TST. The anti-immobility effect of creatine (1 mg/kg, po) or ketamine (a fast-acting antidepressant, 1 mg/kg, ip) in the TST was prevented by pretreatment of mice with caffeine (3 mg/kg, ip, nonselective adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (2 mg/kg, ip, selective adenosine A1 receptor antagonist), and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)-phenol (ZM241385) (1 mg/kg, ip, selective adenosine A2A receptor antagonist). In addition, the combined administration of subeffective doses of creatine and adenosine (0.1 mg/kg, ip, nonselective adenosine receptor agonist) or inosine (0.1 mg/kg, ip, nucleoside formed by the breakdown of adenosine) reduced immobility time in the TST. Moreover, the administration of subeffective doses of creatine or ketamine combined with N-6-cyclohexyladenosine (CHA) (0.05 mg/kg, ip, selective adenosine A1 receptor agonist), N-6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)ethyl]adenosine (DPMA) (0.1 mg/kg, ip, selective adenosine A2A receptor agonist), or dipyridamole (0.1 μg/mouse, icv, adenosine transporter inhibitor) produced a synergistic antidepressant-like effect in the TST. These results indicate that creatine, similarly to ketamine, exhibits antidepressant-like effect in the TST probably mediated by the activation of both adenosine A1 and A2A receptors, further reinforcing the potential of targeting the purinergic system to the management of mood disorders.

  9. Clinical effectiveness of usual care with or without antidepressant medication for primary care patients with minor or mild-major depression: a randomized equivalence trial

    Directory of Open Access Journals (Sweden)

    van Dyck Richard

    2007-12-01

    Full Text Available Abstract Background Minor and mild-major depression are highly prevalent in primary care. There is insufficient evidence for the effectiveness of antidepressants in the treatment of minor and mild-major depression. We compared the effectiveness of usual primary care treatment, with or without antidepressants, in minor and mild-major depression. Methods A pragmatic patient-randomized equivalence trial with 52 weeks follow-up was conducted in The Netherlands. In total, 59 primary care physicians (PCPs recruited and treated 181 adult patients with minor or mild-major depression. Patients were randomized to four consultations within 3 months of usual care plus antidepressants (UCandAD or usual care alone (UCnoAD. The Montgomery Åsberg Depression Rating Scale (MADRS was used to assess changes in severity of depressive symptoms. The predefined equivalence margin was set at five points. Multilevel analysis was used to analyze the data. Secondary outcome measures were the Short-Form 36 (SF-36, and the Client Satisfaction Questionnaire (CSQ-8. Results Patients received on average 3.0 (SD 1.4 15-min consultations within 3 months with (n = 85 or without paroxetine (n = 96. Equivalence of UCandAD and UCnoAD was demonstrated in the intention-to-treat analyses as well as the per-protocol analysis after 6 weeks, but not at 13, 26 and 52 weeks follow-up. No statistical differences in effectiveness between treatment groups were found in the intention-to-treat analysis. No differences in the physical and mental functioning (SF-36 were found between the treatment groups. Patients allocated to UCandAD were slightly more satisfied with their treatment at 13 weeks follow-up (but not at 52 weeks follow-up than patients allocated to UCnoAD. Preliminary analyses suggested that subgroups such as patients with mild-major (instead of a minor depression might benefit from antidepressant treatment. Patients who were assigned to their preferred treatment (in particular to

  10. Antidepressant short-term and long-term brain effects during self-referential processing in major depression.

    Science.gov (United States)

    Delaveau, Pauline; Jabourian, Maritza; Lemogne, Cédric; Allaïli, Najib; Choucha, Walid; Girault, Nathalie; Lehericy, Stéphane; Laredo, Judith; Fossati, Philippe

    2016-01-30

    Acute depression is associated with impaired self-referential processing. Antidepressant effects on the neural bases of self-referential processing in depression are unknown. This study aimed to assess short- and long-term effects of agomelatine on these neural bases in depressed patients and the association between pre-treatment brain activation and remission of depression 6 months later. We conducted a randomized double-blind, placebo-controlled, functional magnetic resonance imaging (fMRI) study during an emotional self-referential task, including three scanning sessions (baseline, after 1 week, and after 7 weeks). Twenty-five depressed outpatients were included, all treated with agomelatine or placebo for 1 week. Then, all patients received agomelatine for 24 weeks. Fourteen matched healthy volunteers (HV) who received placebo for 1 week were also included. After 7 days, only depressed patients receiving agomelatine significantly deactivated the ventrolateral prefrontal cortex during self-referential processing, as observed in HV at baseline. After 7 weeks, depressed patients significantly increased the activation of the ventral anterior cingulate cortex. Finally dorsomedial prefrontal cortex and precuneus activations at baseline significantly separated remitters from non-remitters at 24 weeks. In depressed patients, agomelatine had short- and long-term effects on brain structures involved in anhedonia and emotional regulation during self-referential processing. Activation of the dorsomedial prefrontal cortex and precuneus could be informative in the development of biomarker-based treatment of major depression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study

    Directory of Open Access Journals (Sweden)

    Gaurav Gupta

    2015-01-01

    Full Text Available The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n=6 for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST; and forced swim test (FST and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p>0.05. Chronic treatment of combination of genistein (10 mg/kg and amitriptyline (5 mg/kg and 10 mg/kg significantly reduced the immobility time as compared to control group (p<0.001 and was comparable to amitriptyline alone (10 mg/kg. However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg and amitriptyline (5 mg/kg were observed. Genistein at its standard dose (10 mg/kg rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg.

  12. Antidepressant-like effects of curcumin in chronic mild stress of rats: involvement of its anti-inflammatory action.

    Science.gov (United States)

    Jiang, Hong; Wang, Zhen; Wang, Yihe; Xie, Kai; Zhang, Qingrui; Luan, Qinsong; Chen, Wenqiang; Liu, Dexiang

    2013-12-02

    Mounting evidence suggests that inflammation may contribute to the pathophysiology of depression. Curcumin, a polyphenol extracted from the plant Curcuma longa, exhibits a number of pharmacological properties, including potent anti-inflammatory action. Hence, the current study aimed to explore the immunomodulatory effects of curcumin in an animal model of chronic mild stress (CMS). Rats were subjected to CMS protocol for a period of 21 days to induce depressive-like behavior. The body weight, sucrose preference and locomotor activity were evaluated. Both RT-PCR and ELISA were used to determine the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the prefrontal cortex and hippocampus. Modulation of nuclear factor-κB (NF-κB) activation was assessed by western blotting. Chronic treatment with curcumin significantly reversed the CMS-induced behavioral abnormalities (reduced sucrose preference and decreased locomotor activity) in stressed rats. Additionally, curcumin effectively inhibited cytokine gene expression at both the mRNA and the protein level and reduced the activation of NF-κB. The study revealed that curcumin exerted antidepressant-like effects in CMS rats, partially due to its anti-inflammatory aptitude. © 2013.

  13. CD4(+) T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes in Rag2(-/-) mice.

    Science.gov (United States)

    Clark, Sarah M; Soroka, Jennifer A; Song, Chang; Li, Xin; Tonelli, Leonardo H

    2016-05-01

    Accumulating evidence supports a role of T cells in behavioral stress responsiveness. Our laboratory previously reported that lymphocyte deficient Rag2(-/-) mice on a BALB/c background display resilience to maladaptive stress responses when compared with immune competent mice in the predator odor exposure (POE) paradigm, while exhibiting similar behavior in a cued fear-conditioning (FC) paradigm. In the present study, Rag2(-/-) mice on a C57BL/6 background were assessed in the same behavioral paradigms, as well as additional tests of anxiety and depressive-like behavior. Furthermore, the effects of naïve CD4(+ ) T cells were evaluated by adoptive transfer of functional cells from nonstressed, wild-type donors to Rag2(-/-) mice. Consistent with our prior results, Rag2(-/-) mice displayed an attenuated startle response after POE. Nevertheless, reconstitution of Rag2(-/-) mice with CD4(+ ) T cells did not modify startle reactivity. Additionally, in contrast with our previous findings, Rag2(-/-) mice showed attenuated fear responses in the FC paradigm compared to wild-type mice and reconstitution with CD4(+ ) T cells promoted fear learning and memory. Notably, reconstitution with CD4(+ ) T cells had anxiolytic and antidepressant-like effects in Rag2(-/-) mice that had not been previously stressed, but had no effect after POE. Taken together, our results support a role of CD4(+ ) T cells in emotionality, but also indicate that they may promote fear responses by enhancing learning and memory processes.

  14. Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice.

    Science.gov (United States)

    Burokas, Aurelijus; Arboleya, Silvia; Moloney, Rachel D; Peterson, Veronica L; Murphy, Kiera; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2017-10-01

    The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior. C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed. Chronic prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS+GOS combination reduced stress-induced corticosterone release. Prebiotics modified specific gene expression in the hippocampus and hypothalamus. Regarding short-chain fatty acid concentrations, prebiotic administration increased cecal acetate and propionate and reduced isobutyrate concentrations, changes that correlated significantly with the positive effects seen on behavior. Moreover, FOS+GOS reduced chronic stress-induced elevations in corticosterone and proinflammatory cytokine levels and depression-like and anxiety-like behavior in addition to normalizing the effects of stress on the microbiota. Taken together, these data strongly suggest a beneficial role of prebiotic treatment for stress-related behaviors. These findings strengthen the evidence base supporting therapeutic targeting of the gut microbiota for brain-gut axis disorders, opening new avenues in the field of nutritional neuropsychopharmacology. Copyright © 2017 Society of Biological Psychiatry. Published by

  15. Ginsenoside Rg3 exerts anti-depressive effect on an NMDA-treated cell model and a chronic mild stress animal model

    Directory of Open Access Journals (Sweden)

    Hualin Zhang

    2017-05-01

    Full Text Available Depression is a common mental disorder and a leading cause of disability. At its most severe, it can lead to suicide. Recently, there has been growing interest in the application of natural herbs for the prevention and treatment of depression. In this report, we found that the ginsenoside active component Rg3 has an apparent antidepressant effect. In N-methyl-d-aspartic acid (NMDA-treated HT22 murine hippocampal neuronal cells, Rg3 recovered proliferation and inhibited apoptosis by altering the cell cycle. More interestingly, Rg3 led to apparent physiological behavior change in a chronic mild stress model as seen in forced swim, tail suspension, and sucrose preference tests. This effect was mediated by the phosphorylation of cAMP response element binding protein (CREB and brain-derived neurotrophic factor (BDNF signaling. This study provides direct evidence to support the antidepressant effects of ginsenoside Rg3, potentially indicating its application in the treatment of clinical depression.

  16. Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants: A Meta-Analysis Following the PRISMA Guidelines.

    Science.gov (United States)

    Li, Dian-Jeng; Tseng, Ping-Tao; Chen, Yen-Wen; Wu, Ching-Kuan; Lin, Pao-Yen

    2016-03-01

    Bupropion is widely used for treating bipolar disorder (BD), and especially those with depressive mood, based on its good treatment effect, safety profile, and lower risk of phase shifting. However, increasing evidence indicates that the safety of bupropion in BD patients may not be as good as previously thought. The aim of this study was to summarize data on the treatment effect and safety profile of bupropion in the treatment of BD via a meta-analysis. Electronic search through PubMed and ClinicalTrials.gov was performed. The inclusion criteria were: (i) studies comparing changes in disease severity before and after bupropion treatment or articles comparing the treatment effect of bupropion in BD patients with those receiving other standard treatments; (ii) articles on clinical trials in humans. The exclusion criteria were (i) case reports/series, and (ii) nonclinical trials. All effect sizes from 10 clinical trials were pooled using a random effects model. We examined the possible confounding variables using meta-regression and subgroup analysis. Bupropion significantly improved the severity of disease in BD patients (P bupropion and those who received other antidepressants. We could not perform a detailed meta-analysis of every category of antidepressant, nor could we rule out the possible confounding effect of concurrent psychotropics or include all drug side effects. Furthermore, the number of studies recruited in the meta-analysis was relatively small. Our findings reconfirm the benefits of bupropion for the treatment of bipolar depression, which are similar to those of other antidepressants. However, the rate of phase shifting with bupropion usage was not as low compared to other antidepressants as previously thought, which should serve to remind clinicians of the risk of phase shifting when prescribing bupropion to BD patients regardless of the suggestions of current clinical practice guidelines.

  17. Antidepressant-like effect of cannabidiol injection into the ventral medial prefrontal cortex-Possible involvement of 5-HT1A and CB1 receptors.

    Science.gov (United States)

    Sartim, A G; Guimarães, F S; Joca, S R L

    2016-04-15

    Systemic administration of cannabidiol (CBD), the main non-psychotomimetic constituent of Cannabis sativa, induces antidepressant-like effects. The mechanism of action of CBD is thought to involve the activation of 5-HT1A receptors and the modulation of endocannabinoid levels with subsequent CB1 activation. The brain regions involved in CBD-induced antidepressant-like effects remain unknown. The ventral medial prefrontal cortex (vmPFC), which includes the infralimbic (IL) and prelimbic (PL) subregions, receives dense serotonergic innervation and plays a significant role in stress responses. To test the hypothesis that the administration of CBD into the IL or PL would induce an antidepressant-like effect through 5-HT1A and CB1 activation. Rats received intra-IL or -PL microinjections of CBD (10-60 nmol/side), 8-OH-DPAT (5-HT1A agonist, 5-10 nmol/side), anandamide (AEA, 0.5 pmol/side) or vehicle (0.2 μl/side) and were submitted to the forced swimming (FST) or to the open field (OFT) tests. Independent CBD-treated groups were pre-treated with WAY100635 (10, 30 nmol/side, 5-HT1A antagonist) or AM251 (10 pmol/side, CB1 antagonist) and submitted to the same tests. An additional group was treated with WAY100635 followed by anandamide. CBD (PL: 10-60 nmol; IL:45-60 nmol) and 8-OH-DPAT (10 nmol) administration significantly reduced the immobility time in the FST, without changing locomotor activity in the OFT. WAY100635 (30 nmol) did not induce effect per se but blocked CBD, 8-OH-DPAT and AEA effects. Additionally, AM251 blocked CBD-effects. administration of CBD into the vmPFC induces antidepressant-like effects possibly through indirect activation of CB1 and 5-HT1A receptors. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Capgras syndrome responding to the antidepressant mirtazapine.

    Science.gov (United States)

    Khouzam, Hani Raoul

    2002-01-01

    A new onset of Capgras syndrome, delusional misidentification, developed in an elderly gentleman. Treatment with the antidepressant mirtazapine led to the remission. Suggestions are made for both dynamic and medical bases for Capgras syndrome and possible antipsychotic effects of mirtazapine.

  19. Placebo and antidepressant treatment for major depression

    DEFF Research Database (Denmark)

    Hougaard, Esben

    2010-01-01

    Antidepressant medication is generally considered the primary treatment for major depressive disorders (MDD), but antidepressant treatment has recently approached a crisis with shrinking specific effects and growing placebo responses in current trials. The aim of the paper is to review the placebo...... problem within antidepressant treatment for MDD, and to draw lines to similar problems within the field of psychotherapy. Although clinicians might profit from the large placebo response in their treatment of MDD, the small differences between active treatment and placebo groups found in controlled...

  20. A retrospective study of predictive factors for effective aripiprazole augmentation of antidepressant therapy in treatment-resistant depression

    Directory of Open Access Journals (Sweden)

    Sugawara H

    2016-05-01

    Full Text Available Hiroko Sugawara,1,2 Kaoru Sakamoto,1 Tsuyoto Harada,3 Satoru Shimizu,4 Jun Ishigooka1 1Department of Psychiatry, Tokyo Women’s Medical University, 2Support Center for Women Health Care Professionals and Researchers, Tokyo Women’s Medical University, Shinjuku-ku, 3Department of Psychiatry, Tokyo Women’s Medical University Medical Center East, Arakawa-ku, 4Department of Research, Medical Research Institute, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan Background: Several studies have evaluated the efficacy and tolerability of aripiprazole for augmentation of antidepressant therapy for treatment-resistant depression (TRD. Here, we investigated the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder and the clinical predictors of treatment efficacy in a Japanese population.  Methods: Eighty-five depressed Japanese patients who underwent aripiprazole augmentation therapy after failing to respond satisfactorily to antidepressant monotherapy were included in the study. Treatment responses were evaluated based on Clinical Global Impression Improvement scores assessed 8 weeks after initiation of aripiprazole administration. We compared demographic and diagnostic variables, psychiatric medication variables, and clinical variables between remission and nonremission groups.  Results: The aripiprazole augmentation remission rate was 36.5%. Multiple logistic regression analysis indicated that aripiprazole augmentation was significantly more effective for bipolar depression than for major depressive disorder, and both absence of comorbid anxiety disorders and current episode duration >3 months were significantly associated with the efficacy of aripiprazole augmentation.  Conclusion: Polarity of depression, comorbidity of anxiety disorders, and current episode duration may predict the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and

  1. Ursolic acid affords antidepressant-like effects in mice through the activation of PKA, PKC, CAMK-II and MEK1/2.

    Science.gov (United States)

    Ramos-Hryb, Ana B; Cunha, Mauricio P; Pazini, Francis L; Lieberknecht, Vicente; Prediger, Rui D S; Kaster, Manuella P; Rodrigues, Ana Lúcia S

    2017-05-24

    Ursolic acid has been shown to display antidepressant-like effects in mice through the modulation of monoaminergic systems. In this study, we sought to investigate the involvement of signaling pathways on the antidepressant-like effects of ursolic acid. Mice were treated orally with ursolic acid (0.1mg/kg) and, 45min later they received the followings inhibitors by intracerebroventricular route: H-89 (PKA inhibitor, 1μg/mouse), KN-62 (CAMK-II inhibitor, 1μg/mouse), chelerythrine (PKC inhibitor, 1μg/mouse), U0126 (MEK1/2 inhibitor, 5μg/mouse), PD98059 (MEK1/2 inhibitor, 5μg/mouse), wortmannin (PI3K irreversible inhibitor, 0.1μg/mouse) or LY294002 (PI3K inhibitor, 10 nmol/mouse). Immobility time of mice was registered in the tail suspension test (TST). The anti-immobility effect of ursolic acid in the TST was abolished by the treatment of mice with H-89, KN-62, chelerythrine, U0126 or PD98059, but not with wortmannin or LY294002. These results suggest that activation of PKA, PKC, CAMK-II, MEK1/2 may underlie the antidepressant-like effects of ursolic acid. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Is nitric oxide signalling involved in the antidepressant action of ketamine?

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Müller, Heidi Kaastrup; Elfving, Betina

    2012-01-01

    Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect in depre......Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect...... in depressed patients following a single intravenous administration that is sustained for ± 7 days. A number of downstream cellular mechanisms appear to mediate the antidepressant action of ketamine, and the majority of evidence point to a rapid activation of protein translation leading to increased synaptic...... receptors, while the uncoupling of the nNOS-NMDA receptor complex prevents NMDA-induced excitotoxicity. Thus, it is possible that the inhibition of nitric oxide (NO) signalling underlies a key upstream mechanism in the antidepressant action of ketamine. Methods: We used a genetic rat model of depression...

  3. EPA and DHA, but not ALA, have antidepressant effects with 17β-estradiol injection via regulation of a neurobiological system in ovariectomized rats.

    Science.gov (United States)

    Choi, Jeong-Eun; Park, Yongsoon

    2017-11-01

    Our previous studies found that n-3 polyunsaturated fatty acids (PUFAs) and estrogen had synergistic antidepressant-like effects. The purpose of the present study was to investigate the hypothesis that three major n-3 PUFAs, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), individually had antidepressant effects combined with 17β-estradiol-3-benzoate (E) through a neurobiological pathway in ovariectomized rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0% n-3 PUFAs and 1% ALA, EPA and DHA relative to total energy intake for 12 weeks and were injected with corn oil or E every 4 days during the last 3 weeks. Supplementation of EPA, DHA and E increased serum concentrations of serotonin and climbing behavior, and decreased immobility during a forced swimming test. Supplementation with EPA, DHA and E also decreased hippocampal expressions of interleukin-6 and tumor necrosis factor-α, and increased cAMP response element binding protein, brain-derived neurotrophic factor (BDNF) and estrogen receptor-α. Immunofluorescence staining consistently showed elevated expressions of BDNF. Magnetic resonance spectroscopy showed that E increased glucose and decreased glutamate, glutamine and myo-inositol concentrations regardless of n-3 PUFA supplementation. In addition, supplementation with EPA, DHA and E decreased levels of nitrite and nitrate. However, ALA had no antidepressant effect. The present study suggested that the antidepressant-like effects of EPA and DHA supplementation and E injection could be due to the regulation of serotonergic neurotransmission and inflammatory cytokines rather than due to the antioxidative system. Supplementation with n-3 PUFA and E had the additional function of modulating neurometabolites in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Role of Bai-Shao towards the antidepressant effect of Chaihu-Shu-Gan-San using metabonomics integrated with chemical fingerprinting.

    Science.gov (United States)

    Chang, Xing; Jia, Hongmei; Zhou, Chao; Zhang, Hongwu; Yu, Meng; Yang, Junshan; Zou, Zhongmei

    2015-12-01

    Chaihu-Shu-Gan-San (CSGS) is a classical traditional Chinese medicine formula for the treatment of depression. As one of the single herbs in CSGS, Bai-Shao displayed antidepressant effect. In order to explore the role of Bai-Shao towards the antidepressant effect of CSGS, the metabolic regulation and chemical profiles of CSGS with and without Bai-Shao (QBS) were investigated using metabonomics integrated with chemical fingerprinting. At first, partial least squares regression (PLSR) analysis was applied to characterize the potential biomarkers associated with chronic unpredictable mild stress (CUMS)-induced depression. Among 46 differential metabolites found in the ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) and (1)H NMR-based urinary metabonomics, 20 were significantly correlated with the preferred sucrose consumption observed in behavior experiments and were considered as biomarkers to evaluate the antidepressant effect of CSGS. Based on differential regulation on CUMS-induced metabolic disturbances with CSGS and QBS treatments, we concluded that Bai-Shao made crucial contribution to CSGS in the improvement of the metabolic deviations of six biomarkers (i.e., glutamate, acetoacetic acid, creatinine, xanthurenic acid, kynurenic acid, and N-acetylserotonin) disturbed in CUMS-induced depression. While the chemical constituents of Bai-Shao contributed to CSGS were paeoniflorin, albiflorin, isomaltopaeoniflorin, and benzoylpaeoniflorin based on the multivariate analysis of the UPLC-Q-TOF/MS chemical profiles from CSGS and QBS extracts. These findings suggested that Bai-Shao played an indispensable role in the antidepressant effect of CSGS. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity.

    Science.gov (United States)

    Li, Qing; Qu, Fa-Lin; Gao, Yue; Jiang, Yi-Ping; Rahman, Khalid; Lee, Kuo-Hsiung; Han, Ting; Qin, Lu-Ping

    2017-03-06

    There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. The results showed that PS extracts (100, 200mg/kg) and PSY (12.5, 25, 50mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  6. Differential effects of antidepressants on glucocorticoid receptors in human primary blood cells and human monocytic U-937 cells.

    Science.gov (United States)

    Heiske, Andreas; Jesberg, Jutta; Krieg, Jürgen-Christian; Vedder, Helmut

    2003-04-01

    A number of data support the assumption that antidepressants (ADs) normalize the altered function of the hypothalamic-pituitary-adrenocortical (HPA) system involved in the pathophysiology of depressive disorder via direct effects on glucocorticoid receptors (GRs). In the present study, we examined the tricyclic ADs desipramine (DESI) and imipramine (IMI), the noradrenaline reuptake inhibitor maprotiline (MAPRO), and the noradrenergic and specific serotonergic AD (NaSSA) mirtazapine (MIR) for their effects on GR expression in primary human leukocytes and in monocytic U-937 cells. Semiquantitative RT-PCR indicated that the ADs exert differential effects on GR-mRNA levels in both primary human leukocytes and U-937 cells: whereas MAPRO and IMI did not induce pronounced changes in GR-mRNA levels, DESI and MIR significantly decreased the amounts of GR-mRNA in both cell systems. Further characterization of the effects of MIR revealed a time dependency of the regulation with an initial increase of GR-mRNA levels above control levels after 2.5 h of treatment and a decrease after 4, 24, and 48 h of incubation. A dose-response analysis demonstrated maximal effects of MIR at a concentration of 10(-7) M. Immunohistochemical studies showed that MIR increased the GR protein levels in a time-dependent manner and that this upregulation appeared earlier by additional treatment with dexamethasone (DEX). A translocation of the GR protein from the cytoplasm to the nucleus was induced between 24 and 48 h of treatment with MIR and MIR/DEX, respectively. Taken together, our data further support the assumption that ADs influence the neuroendocrine and immune system via effects on cellular GRs.

  7. Effect of tricyclic antidepressants on transmitter-stimulated inositol phosphate production in rat brain cortex in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, S.; Enna, S.J.

    1986-03-01

    Tricyclic antidepressants (TCAs) have anticholinergic and ..cap alpha..-adrenergic blocking properties. The present study was undertaken to examine the effects of amitriptyline, imipramine, and desipramine on inositol phosphate accumulation, a brain second messenger system associated with cholinergic and adrenergic receptors. Whereas the TCAs were 28 to 400-fold weaker than atropine as inhibitors of /sup 3/H-QNB binding to brain cholinergic receptors, they were 600 to 2000-fold less active than atropine as inhibitors of carbachol-stimulated IP accumulation in brain. In contrast, the relative potencies of the TCAs and prazosin to inhibit norepinephrine-stimulated IP accumulation and /sup 3/H-prazosin binding appeared to be similar in the two assays. The results suggest pharmacological differences between the cholinergic receptors labeled in the ONB binding assay and those mediating the IP response, whereas the ..cap alpha../sub 1/-adrenergic receptors appear to be similar in the two systems. Since atropine is considered a nonselective muscarinic antagonist, it is possible that the TCAs may differentiate between cholinergic receptor subtypes, which may be an important component of their clinical response.

  8. Antidepressant medication use and breast cancer risk.

    Science.gov (United States)

    Wernli, Karen J; Hampton, John M; Trentham-Dietz, Amy; Newcomb, Polly A

    2009-04-01

    Most epidemiologic studies have detected no association between prior use of antidepressant medications and breast cancer risk. Despite the uniform conclusion, there is a continuous rise in the proportion of women using antidepressants, lending support to further monitoring of disease effects. We conducted a population-based case-control study among 2908 incident breast cancer cases diagnosed from 2003 to 2006, and 2927 control women from Wisconsin. Associations between antidepressant use and breast cancer risk were evaluated using multivariable logistic regression. The association between use of antidepressant medications and breast cancer risk was null (OR = 0.89, 95%CI 0.78-1.01). When stratified by type of antidepressant, use of selective-serotonin reuptake inhibitors (SSRIs) resulted in a similar risk overall (OR = 0.85, 95%CI 0.72-1.00) and among former and currents users. There were no associations between other types of antidepressant classes and breast cancer risk. In assessing risks among the five most commonly used antidepressants, we detected no association with fluoxetine, sertraline, venlafaxine, or buproprion hydrochloride. There was a reduction in breast cancer risk of 36% (OR = 0.64, 95%CI 0.45-0.92) among users of paroxetine hydrochloride. When stratified by body mass index, there was a reduction in risk associated with antidepressant users who were not overweight (OR = 0.73, 95% CI 0.60-0.90), but this association was null in overweight women (p-interaction = 0.04). Surveillance of health risks associated with antidepressant medications continues to be of public health importance, though these medications are not likely to be associated with breast cancer risk.

  9. The effect of combined treatment with risperidone and antidepressants on the MK-801-induced deficits in the social interaction test in rats.

    Science.gov (United States)

    Kamińska, Katarzyna; Rogóż, Zofia

    2015-12-01

    Several clinical reports have suggested that augmentation of atypical antipsychotics' activity by antidepressants may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. The aim of the present study was to investigate the effect of antidepressant mirtazapine or escitalopram and risperidone (an atypical antipsychotic), given separately or jointly, on the MK-801-induced deficits in the social interaction test in rats. Antidepressants and risperidone were given 60 and 30 min before the test, respectively. The social interaction of male Wistar rats was measured for 10 min, starting 4 h after MK-801 (0.1 mg/kg) administration. In the social interaction test, MK-801-induced deficits in the parameters studied, i.e. the number of episodes and the time of interactions. Risperidone at a higher dose (0.1 mg/kg) reversed that effect. Co-treatment with an ineffective dose of risperidone (0.01 mg/kg) and mirtazapine (2.5 or 5 mg/kg) or escitalopram only at a dose of 5 mg/kg (but not 2.5 and 10 mg/kg) abolished the deficits evoked by MK-801. The obtained results suggest that especially mirtazapine, and to a smaller degree escitalopram may enhance the antipsychotic-like effect of risperidone in the animal test modeling some negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. Involvement of PKA, PKC, CAMK-II and MEK1/2 in the acute antidepressant-like effect of creatine in mice.

    Science.gov (United States)

    Cunha, Mauricio P; Budni, Josiane; Pazini, Francis L; Oliveira, Ágatha; Rosa, Julia M; Lopes, Mark W; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

    2014-08-01

    The aim of this study was to investigate the involvement of signaling pathways on the creatine antidepressant-like effect in the tail suspension test (TST) in mice. The TST was used to assess the antidepressant-like properties of creatine. The anti-immobility effect of creatine (1mg/kg, p.o.) in the TST was blocked by i.c.v. pretreatment with H-89 (1μg/site, PKA inhibitor), KN-62 (1μg/site, CAMK-II inhibitor), chelerythrine (1μg/site, PKC inhibitor), U0126 (5μg/site, MEK1/2 inhibitor) or PD09058 (5μg/site, MEK1/2 inhibitor). These results suggest that the antidepressant-like effect of creatine is dependent on PKA, CaMK-II, PKC and MEK 1/2 activation. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Multiple antidepressant potential modes of action of curcumin: a review of its anti-inflammatory, monoaminergic, antioxidant, immune-modulating and neuroprotective effects.

    Science.gov (United States)

    Lopresti, Adrian L; Hood, Sean D; Drummond, Peter D

    2012-12-01

    Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus-pituitary-adrenal disturbances, lowering inflammation and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.

  12. Antidepressant-like Effect of l-perillaldehyde in Stress-induced Depression-like Model Mice through Regulation of the Olfactory Nervous System

    Directory of Open Access Journals (Sweden)

    N. Ito

    2011-01-01

    Full Text Available Perillae Herba (a leaf of Perilla frutescens has been prescribed as one of the component herbs in certain Kampo (Japanese herbal medicines that are used clinically for the improvement of depressive mood. l-Perillaldehyde (PAH is a major component in the essential oil containing in Perillae Herba, but its antidepressant-like effect has not been reported. To clarify the antidepressant-like effect of PAH, the inhaled effect of PAH on stress-induced depression-like model mice prepared by subjection to a combination of forced swimming and chronic mild stresses was investigated. The degree of the depression-like state was measured by the animal's duration of immobility using a forced swimming test. Inhalation of PAH (0.0965 and 0.965 mg/mouse/day, 9 days significantly shortened the duration of immobility of the depression-like model mice and did not affect locomotor activity. However, another odor substance, cinnamaldehyde containing in Cinnamomi Cortex, exhibited no reduction in the immobility. The reduction in the immobility induced by the inhalation of PAH was prevented on anosmia-induced mice prepared by intranasal irrigation with zinc sulfate. These results suggest that the inhalation of PAH shows antidepressant-like activity through the olfactory nervous function.

  13. Antidepressant-like effect of bis-eugenol in the mice forced swimming test: evidence for the involvement of the monoaminergic system.

    Science.gov (United States)

    do Amaral, Jeferson Falcão; Silva, Maria Izabel Gomes; de Aquino Neto, Manuel Rufino; Moura, Brinell Arcanjo; de Carvalho, Alyne Mara Rodrigues; Vasconcelos, Patrícia Freire; Barbosa Filho, José Maria; Gutierrez, Stanley Juan Chavez; Vasconcelos, Silvânia Maria Mendes; Macêdo, Danielle Silveira; de Sousa, Francisca Cléa Florenço

    2013-10-01

    Dehydrodieugenol, known as bis-eugenol, is a eugenol ortho dimer, and both compounds were able to exhibit anti-inflammatory and antioxidant activities in previous studies. Furthermore, eugenol showed antidepressant-like effect; however, the biological actions of bis-eugenol on experimental models for screening antidepressant activity are still unknown. The present study investigated a possible antidepressant-like activity of bis-eugenol in the forced swimming test (FST) and tail suspension test (TST) in mice and the involvement in the monoaminergic system in this effect. In addition, a neurochemical analysis on brain monoamines of mice acutely treated with bis-eugenol was also conducted. Bis-eugenol decreased the immobility time in the FST and TST without accompanying changes in ambulation in the open field test at 10 mg/kg, i.p.. Nevertheless, it induced ambulation at 25 and 50 mg/kg doses. The anti-immobility effect of bis-eugenol (10 and 50 mg/kg, i.p.) was prevented by pretreatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), SCH23390 (15 μg/kg, s.c., a dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist). Monoamines analysis using high-performance liquid chromatograph revealed significant increase in the 5-HT, NE and DA levels in brain striatum. The present study indicates that bis-eugenol possesses antidepressant-like activity in FST and TST by altering dopaminergic, serotonergic and noradrenergic systems function. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  14. Use of Antidepressants

    Science.gov (United States)

    Kalali, Amir H.; Thase, Michael E.

    2007-01-01

    We investigated antidepressant prescriptions and reasons for use. According to our data, the top 10 molecules represent ∼95% of total antidepressant prescriptions for both primary care physicians (PCPs) and psychiatrists. The primary difference between PCPs and psychiatrists was the increased use of buproprion and tricyclics/tetracyclics by psychiatrists. The selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants such as venlafaxine (Effexor) and buproprion (Wellbutrin) are used to treat depression, anxiety, and bipolar disorders. The noted exception is duloxetine (Cymbalta), which looks like a blend between the newer agents and the tricyclics where there is use beyond the traditional central nervous system (CNS) disorders into pain and migraine. PMID:20436760

  15. Hesperidin exerts antidepressant-like effects in acute and chronic treatments in mice: possible role of l-arginine-NO-cGMP pathway and BDNF levels.

    Science.gov (United States)

    Donato, Franciele; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Filho, Carlos Borges; Del Fabbro, Lucian; Antunes, Michelle S; Souza, Leandro Cattelan; Boeira, Silvana Peterini; Jesse, Cristiano Ricardo

    2014-05-01

    Hesperidin (4'-methoxy-7-O-rutinosyl-3',5-dihydroxyflavanone), a naturally occurring flavanone glycoside, was previously shown to produce an antidepressant-like effect with modultation of the serotonergic 5-HT1A and kappa-opioid receptors. In this study, the signaling mechanisms underlying their antidepressant-like effects were further evaluated by investigating in acute and chronic treatments. Results showed that chronic treatment of hesperidin or hesperitin (0.1, 0.3 and 1mg/kg, intraperitoneal, i.p.) have an antidepressant-like effect in the mouse tail suspension test (TST) without modified the locomotor activity in the open field test. Pretreatment with l-arginine (a nitric oxide (NO) precursor), sildenafil (a phosphodiesterase 5 inhibitor) or S-nitroso-N-acetyl-penicillamine (a NO donor) significantly reversed the reduction in immobility time elicited by acute treatment with hesperidin (0.3mg/kg) in the TST. Hesperidin (0.01mg/kg, a sub-effective dose in acute treatment) produced an additive antidepressant-like effect with N(G)-nitro-l-arginine (an inhibitor of nitric oxide synthase (NOS)) or 7-nitroindazole (a neuronal NOS inhibitor) in the TST. Pretreatment of animals with methylene blue (an inhibitor of NOS/soluble guanylate cyclase (sGC)) or ODQ (a specific inhibitor sGS) caused an additive effect with hesperidin in the TST. Hesperidin in the acute (1mg/kg) and chronic (0.1, 0.3 and 1mg/kg) treatments caused a significant decrease in nitrate/nitrite (NOX) levels in the hippocampus of mice. Chronic treatment with hesperidin (0.3 and 1mg/kg) also resulted in an increase in hippocampal brain-derived neurotrophic factor (BDNF) levels. These results demonstrated that the antidepressant-like effect of hesperidin is likely mediated by inhibition of l-arginine-NO-cGMP pathway and by increased of the BDNF levels in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Anti-anxiety and Anti-depressant Like Effects of Murraya koenigii in Experimental Models of Anxiety and Depression

    Science.gov (United States)

    Sharma, Snigdha; Handu, Shailendra; Dubey, Ashok Kumar; Sharma, Prashant; Mediratta, Pramod; Ahmed, Qazi Mushtaq

    2017-01-01

    Background: Presence of free radical scavenging activity in Murraya koenigii, commonly known as Curry leaves, has been shown in previous studies. Oxidative stress plays an important role in the development of various neurobehavioral disorders including anxiety and depression. Aim: The present study aimed to evaluate the effects of Murraya koenigii in animal models of depression and anxiety. Materials and Methods: The effect of incremental doses of Murraya koenigii aqueous leaf extract was evaluated on spontaneous motor activity (SMA), open arm incursions in elevated plus maze, and despair behaviour in forced swim (FST) and tail suspension (TST) tests as compared to control groups in Swiss albino mice. Results: Murraya koenigii 300 mg/kg, p.o. (MK300) and 400 mg/kg, p.o. (MK400) reduced the SMA count from 754 ± 64.9 to 540 ± 29 and 295 ± 34 respectively, which was statistically significant. MK300 and MK400 reduced significantly the open arm count from 29 ± 8.6 to 16 ± 7 and 10 ± 3.9, respectively. On FST, MK400 reduced the duration of immobility from 145.5 ± 29 to 91 ± 17.3, which was statistically significant. On TST, MK produced a dose-dependent decrease in the duration of immobility; however, it was statistically significant only with MK400. Conclusion: Murraya koenigii aqueous leaf extract reduced the despair behavior in experimental animal models, suggesting an anti-depressant like activity. Murraya koenigii extract also reduced spontaneous locomotor activity in a dose-dependent manner suggesting a sedative and/or anxiolytic effect though there wasn’t any anxiolytic effect in the elevated plus maze test. PMID:29269974

  17. Anti-anxiety and Anti-depressant Like Effects ofMurraya koenigiiin Experimental Models of Anxiety and Depression.

    Science.gov (United States)

    Sharma, Snigdha; Handu, Shailendra; Dubey, Ashok Kumar; Sharma, Prashant; Mediratta, Pramod; Ahmed, Qazi Mushtaq

    2017-01-01

    Presence of free radical scavenging activity in Murraya koenigii , commonly known as Curry leaves, has been shown in previous studies. Oxidative stress plays an important role in the development of various neurobehavioral disorders including anxiety and depression. The present study aimed to evaluate the effects of Murraya koenigii in animal models of depression and anxiety. The effect of incremental doses of Murraya koenigii aqueous leaf extract was evaluated on spontaneous motor activity (SMA), open arm incursions in elevated plus maze, and despair behaviour in forced swim (FST) and tail suspension (TST) tests as compared to control groups in Swiss albino mice. Murraya koenigii 300 mg/kg, p.o. (MK300) and 400 mg/kg, p.o. (MK400) reduced the SMA count from 754 ± 64.9 to 540 ± 29 and 295 ± 34 respectively, which was statistically significant. MK300 and MK400 reduced significantly the open arm count from 29 ± 8.6 to 16 ± 7 and 10 ± 3.9, respectively. On FST, MK400 reduced the duration of immobility from 145.5 ± 29 to 91 ± 17.3, which was statistically significant. On TST, MK produced a dose-dependent decrease in the duration of immobility; however, it was statistically significant only with MK400. Murraya koenigii aqueous leaf extract reduced the despair behavior in experimental animal models, suggesting an anti-depressant like activity. Murraya koenigii extract also reduced spontaneous locomotor activity in a dose-dependent manner suggesting a sedative and/or anxiolytic effect though there wasn't any anxiolytic effect in the elevated plus maze test.

  18. Anti-anxiety and anti-depressant like effects of murraya koenigii in experimental models of anxiety and depression

    Directory of Open Access Journals (Sweden)

    Snigdha Sharma

    2017-01-01

    Full Text Available Background: Presence of free radical scavenging activity in Murraya koenigii, commonly known as Curry leaves, has been shown in previous studies. Oxidative stress plays an important role in the development of various neurobehavioral disorders including anxiety and depression. Aim: The present study aimed to evaluate the effects of Murraya koenigii in animal models of depression and anxiety. Materials and Methods: The effect of incremental doses of Murraya koenigii aqueous leaf extract was evaluated on spontaneous motor activity (SMA, open arm incursions in elevated plus maze, and despair behaviour in forced swim (FST and tail suspension (TST tests as compared to control groups in Swiss albino mice. Results: Murraya koenigii 300 mg/kg, p.o. (MK300 and 400 mg/kg, p.o. (MK400 reduced the SMA count from 754 ± 64.9 to 540 ± 29 and 295 ± 34 respectively, which was statistically significant. MK300 and MK400 reduced significantly the open arm count from 29 ± 8.6 to 16 ± 7 and 10 ± 3.9, respectively. On FST, MK400 reduced the duration of immobility from 145.5 ± 29 to 91 ± 17.3, which was statistically significant. On TST, MK produced a dose-dependent decrease in the duration of immobility; however, it was statistically significant only with MK400. Conclusion: Murraya koenigii aqueous leaf extract reduced the despair behavior in experimental animal models, suggesting an anti-depressant like activity. Murraya koenigii extract also reduced spontaneous locomotor activity in a dose-dependent manner suggesting a sedative and/or anxiolytic effect though there wasn't any anxiolytic effect in the elevated plus maze test.

  19. A selective inhibitor of protein kinase A induces behavioural and neurological antidepressant-like effect in rats

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Müller, Heidi Kaastrup; Elfving, Betina

    2011-01-01

    demonstrated antidepressant-like activity following the direct activation of PKA [3]. In this project we critically evaluate this notion by investigating the mood-altering actions of a PKA inhibitor, Rp-8-Br-cAMPS, in the rat forced swim test (FST) while correlating these results with the cAMP concentration...... such as the activation of exchange protein directly activated by cAMP (Epac) 1 and 2 that subsequently activates Rap-1, a member of the Ras family of small GTPases with a variety of important physiological functions. Nonetheless, the data from this study challenge the general notion that the antidepressant-like activity...

  20. Role of the amygdala in antidepressant effects on hippocampal cell proliferation and survival and on depression-like behavior in the rat.

    Directory of Open Access Journals (Sweden)

    Jorge E Castro

    Full Text Available The stimulation of adult hippocampal neurogenesis by antidepressants has been associated with multiple molecular pathways, but the potential influence exerted by other brain areas has received much less attention. The basolateral complex of the amygdala (BLA, a region involved in anxiety and a site of action of antidepressants, has been implicated in both basal and stress-induced changes in neural plasticity in the dentate gyrus. We investigated here whether the BLA modulates the effects of the SSRI antidepressant fluoxetine on hippocampal cell proliferation and survival in relation to a behavioral index of depression-like behavior (forced swim test. We used a lesion approach targeting the BLA along with a chronic treatment with fluoxetine, and monitored basal anxiety levels given the important role of this behavioral trait in the progress of depression. Chronic fluoxetine treatment had a positive effect on hippocampal cell survival only when the BLA was lesioned. Anxiety was related to hippocampal cell survival in opposite ways in sham- and BLA-lesioned animals (i.e., negatively in sham- and positively in BLA-lesioned animals. Both BLA lesions and low anxiety were critical factors to enable a negative relationship between cell proliferation and depression-like behavior. Therefore, our study highlights a role for the amygdala on fluoxetine-stimulated cell survival and on the establishment of a link between cell proliferation and depression-like behavior. It also reveals an important modulatory role for anxiety on cell proliferation involving both BLA-dependent and -independent mechanisms. Our findings underscore the amygdala as a potential target to modulate antidepressants' action in hippocampal neurogenesis and in their link to depression-like behaviors.

  1. Effect of Part D coverage restrictions for antidepressants, antipsychotics, and cholinesterase inhibitors on related nursing home resident outcomes.

    Science.gov (United States)

    Stevenson, David G; O'Malley, A James; Dusetzina, Stacie B; Mitchell, Susan L; Zarowitz, Barbara J; Chernew, Michael E; Newhouse, Joseph P; Huskamp, Haiden A

    2014-09-01

    In 2006, Medicare Part D transitioned prescription drug coverage for dual-eligible nursing home residents from Medicaid to Medicare and randomly assigned them to Part D prescription drug plans (PDPs). Because PDPs may differ in coverage, plans may be more or less generous for drugs that an individual is taking. Taking advantage of the fact that randomization mitigates potential selection bias common in observational studies, this study sought to assess the effect of PDP coverage on resident outcomes for three medication classes--antidepressants, antipsychotics, and cholinesterase inhibitors. Retrospective cohort study to examine the effect of coverage restrictions--including noncoverage and coverage with restrictions--on depression, hallucinations and delusions, aggressive behaviors, cognitive performance, and activities of daily living for dual-eligible nursing home residents randomized to PDPs in 2006 to 2008. The analyses further adjusted for baseline health status to address any residual imbalances in the comparison groups. Linked data from Medicare claims, Minimum Data Set assessments, pharmacy claims, and PDP formulary information. Dual-eligible nursing home residents aged 65 and older living in facilities that contracted with a single pharmacy provider. PDP coverage restrictions in three medication classes of interest were not significantly associated with the resident outcomes examined. Although cholinesterase inhibitor users facing coverage restrictions had a 0.04-point lower depression rating score than residents facing no restrictions, this difference was not statistically significant after adjusting for multiple comparisons. The findings suggest that exogenous changes in coverage for three commonly used medication classes had no detectable effect on nursing home resident outcomes in 2006 to 2008. There are several possible explanations for this lack of association, including the role of policy protections for dual-eligible nursing home residents and the

  2. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline.

    Science.gov (United States)

    Waldinger, M D; Hengeveld, M W; Zwinderman, A H; Olivier, B

    1998-08-01

    Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p IELT IELT > 1 minute) to investigate whether data about SSRI-induced delayed ejaculation in men with rapid ejaculation may be extrapolated to men with less-rapid ejaculation. After measurement of IELT at home (using a stopwatch) during a 1-month baseline assessment, 32 men with an IELT of 1 minute or less (group 1) or more than 1 minute (group 2) were randomly assigned to receive paroxetine 20 mg/day or placebo for 6 weeks in a double-blind manner. Patients continued to measure their IELTs at home during the 6 weeks of the study. At baseline, 24 patients consistently had IELTs of one minute or less (group 1), and eight patients

  3. Antidepressant-Induced Sleep Bruxism: Prevalence, Incidence, and Related Factors.

    Science.gov (United States)

    Uca, Ali Ulvi; Uğuz, Faruk; Kozak, Hasan Hüseyin; Gümüş, Haluk; Aksoy, Fadime; Seyithanoğlu, Abdullah; Kurt, Hatice Güncü

    2015-01-01

    The relationship between sleep bruxism and antidepressant drugs in patients remains unclear. In this study, we aimed to investigate the incidence rate of antidepressant-related bruxism and to examine whether antidepressant use is associated with this adverse effect in the patients. The study sample was gathered from 2 hospitals. A total of 807 patients who met the inclusion criteria were included in the study. The sample was divided into 2 groups: the antidepressant group (n = 506) and the control group (n = 301). Sleep bruxism was established with reports from the study participants on the basis of the International Classification of Sleep Disorders: Diagnosis and Coding Manual Second Edition. The prevalence of bruxism was significantly higher in the antidepressant group (24.3%) than in the control group (15.3%). The incidence of antidepressant-induced bruxism was 14.0%. The antidepressants most associated with bruxism were paroxetine, venlafaxine, and duloxetine. The patients experiencing antidepressant-induced bruxism had higher age compared with those who did not experience this adverse effect. The results of the present study suggest that bruxism is frequently observed in women taking antidepressants and that it seems to be associated with antidepressant use at least in some patients.

  4. Single treatments that have lasting effects: some thoughts on the antidepressant effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin.

    Science.gov (United States)

    Young, Simon N

    2013-03-01

    Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research with animal models of depression suggesting that glutamate may be involved in depression, the N-methyl-D-aspartate antagonist ketamine has been tested in several trials. A single dose decreased depression for up to a week. The reported effects of the use of mushrooms containing psilocybin by a number of cultures around the world has stimulated several trials showing beneficial effects of a single dose of psilocybin for over a year in healthy people, and for up to 3 months in patients with anxiety disorders who have advanced cancer. This article discusses these studies, their rationale, their possible mechanisms of action, the future clinical research required to establish these therapies and the basic research required to optimize single treatments that have lasting effects.

  5. Antidepressants but not antipsychotics have antiepileptogenic effects with limited effects on comorbid depressive-like behaviour in the WAG/Rij rat model of absence epilepsy.

    Science.gov (United States)

    Citraro, Rita; Leo, Antonio; De Fazio, Pasquale; De Sarro, Giovambattista; Russo, Emilio

    2015-06-01

    Two of the most relevant unmet needs in epilepsy are represented by the development of disease-modifying drugs able to affect epileptogenesis and/or the study of related neuropsychiatric comorbidities. No systematic study has investigated the effects of chronic treatment with antipsychotics or antidepressants on epileptogenesis. However, such drugs are known to influence seizure threshold. We evaluated the effects of an early long-term treatment (ELTT; 17 weeks), started before seizure onset (P45), with fluoxetine (selective 5-HT-reuptake inhibitor), duloxetine (dual-acting 5-HT-noradrenaline reuptake inhibitor), haloperidol (typical antipsychotic drug), risperidone and quetiapine (atypical antipsychotic drugs) on the development of absence seizures and comorbid depressive-like behaviour in the WAG/Rij rat model. Furthermore, we studied the effects of these drugs on established absence seizures in adult (6-month-old) rats after a chronic 7 weeks treatment. ELTT with all antipsychotics did not affect the development of seizures, whereas, both ELTT haloperidol (1 mg · kg(-1) day(-1)) and risperidone (0.5 mg · kg(-1) day(-1)) increased immobility time in the forced swimming test and increased absence seizures only in adult rats (7 weeks treatment). In contrast, both fluoxetine (30 mg · kg(-1) day(-1)) and duloxetine (10-30 mg · kg(-1) day(-1)) exhibited clear antiepileptogenic effects. Duloxetine decreased and fluoxetine increased absence seizures in adult rats. Duloxetine did not affect immobility time; fluoxetine 30 mg · kg(-1) day(-1) reduced immobility time while at 10 mg · kg(-1) day(-1) an increase was observed. In this animal model, antipsychotics had no antiepileptogenic effects and might worsen depressive-like comorbidity, while antidepressants have potential antiepileptogenic effects even though they have limited effects on comorbid depressive-like behaviour. © 2015 The British Pharmacological Society.

  6. Effects of eliminating drug caps on racial differences in antidepressant use among dual enrollees with diabetes and depression.

    Science.gov (United States)

    Adams, Alyce S; Soumerai, Stephen B; Zhang, Fang; Gilden, Daniel; Burns, Marguerite; Huskamp, Haiden A; Trinacty, Connie; Alegria, Margarita; LeCates, Robert F; Griggs, Jennifer J; Ross-Degnan, Dennis; Madden, Jeanne M

    2015-03-01

    Black patients with diabetes are at greater risk of underuse of antidepressants even when they have equal access to health insurance. This study aimed to evaluate the impact of removing a significant financial barrier to prescription medications (drug caps) on existing black-white disparities in antidepressant treatment rates among patients with diabetes and comorbid depression. We used an interrupted time series with comparison series design and a 5% representative sample of all fee-for-service Medicare and Medicaid dual enrollees to evaluate the removal of drug caps on monthly antidepressant treatment rates. We evaluated the impact of drug cap removal on racial gaps in treatment by modeling the month-to-month white-black difference in use within age strata (younger than 65 years of age or 65 years of age or older). We compared adult dual enrollees with diabetes and comorbid depression living in states with strict drug caps (n = 221) and those without drug caps (n = 1133) before the policy change. Our primary outcome measures were the proportion of patients with any antidepressant use per month and the mean standardized monthly doses (SMDs) of antidepressants per month. The removal of drug caps in strict drug cap states was associated with a sudden increase in the proportion of patients treated for depression (4 percentage points; 95% CI, 0.03-0.05, P < 0.0001) and in the intensity of antidepressant use (SMD: 0.05; 95% CI, 0.03-0.07, P < 0.001). Although antidepressant treatment rates increased for both white and black patients, the white-black treatment gap increased immediately after Part D (0.04 percentage points; 95% CI, 0.01-0.08) and grew over time (0.04 percentage points per month; 95% CI, 0.002-0.01; P < 0.001). Policies that remove financial barriers to medications may increase depression treatment rates among patients with diabetes overall while exacerbating treatment disparities. Tailored outreach may be needed to address nonfinancial barriers to mental

  7. Duality of Antidepressants and Neuroprotectants.

    Science.gov (United States)

    Tizabi, Yousef

    2016-07-01

    The co-morbidity of neuropsychiatric disorders, particularly major depressive disorder (MDD) with neurodegenerative diseases, in particular Parkinson's disease (PD) is now well recognized. Indeed, it is suggested that depressive disorders, especially in late life, may be an indication of latent neurodegeneration. Thus, it is not unreasonable to expect that deterrents of MDD may also deter the onset and/or progression of the neurodegenerative diseases including PD. In this review, examples of neuroprotective efficacy of established as well as prospective antidepressants are provided. Conversely, mood-regulating effects of some neuroprotective drugs are also presented. Thus, in addition to currently used antidepressants, ketamine, nicotine, curcumin, and resveratrol are discussed for their dual efficacy. In addition, potential neurobiological substrates for their actions are presented. It is concluded that pharmacological developments of mood-regulating or neuroprotective drugs can have cross benefit in co-morbid conditions of neuropsychiatric and neurodegenerative disorders and that inflammatory and neurotrophic factors play important roles in both conditions.

  8. Effects of Antidepressants, but not Psychopathology, on Cardiac Sympathetic Control : A Longitudinal Study

    NARCIS (Netherlands)

    Licht, Carmilla M. M.; Penninx, Brenda W. J. H.; de Geus, Eco J. C.

    2012-01-01

    Increased sympathetic activity has been hypothesized to have a role in the elevated somatic disease risk in persons with depressive or anxiety disorders. However, it remains unclear whether increased sympathetic activity reflects a direct effect of anxiety or depression or an indirect effect of

  9. Apatia multimodal iatrogênica Multimodal apathy: a unique effect of antidepressant therapy at the neurological-psychiatric interface

    Directory of Open Access Journals (Sweden)

    Ricardo de Oliveira-Souza

    1996-06-01

    Full Text Available O presente trabalho documenta um efeito peculiar dos antidepressivos em 5 pacientes - a apatia -, definida pela incapacidade de experimentar emoções. O reconhecimento da apatia no curso de tratamento antidepressivo deve levantar a possibilidade de iatrogenia e suspensão do antidepressivo em uso. Frizamos que a apatia deve ser diferenciada da abulia e da avolição, com as quais é comumente contundida. Documentamos que a indiferença emocional pode se confinar a um domínio sensorial ("apatia unimodal" ou, como em nossos casos, a mais de uma modalidade ("apatia multimodal". Circuitos anterobasais, centrados na amígdala e no pólo temporal, são fortes candidatos para integrar a experiência emocional às imagens mentais e percepções multimodais do ambiente, uma vez que para eles convergem os principais sistemas de projeção do prosencéfalo, ao mesmo tempo em que se situam em pontos estratégicos para modular o córtex pré-frontal e parieto-têmporo-occipital. O fato de que a apatia foi produzida por classes quimicamente distintas, como ISRSs (inibidores seletivos de recaptação da serotonina, IMAOs (inibidores reversíveis da monoamino oxidase e tricíclicos, indica que a fisiopatologia em jogo se deve a alguma ação compartilhada por essas drogas no plano subneuronal. A intervenção em circuitos serotoninérgicos cerebrais parece o mecanismo mais adequado para explicar tal efeito.The present paper reports on five patients who developed apathy as a peculiar side effect of antidepressants. Their behavioral and psychopathological changes were primarily due to the near-absence of emotional experience, a key characteristic that distinguishes apathy from avolition and abulia. The emergence of apathy in the course of an antidepressant treatment should raise the suspicion of an adverse effect of the drug and lead to its prompt withdrawal. A sample of the relevant clinical evidence favoring the distinction of apathy confined to a single

  10. Women's experiences of coping with the sexual side effects of antidepressant medication.

    Science.gov (United States)

    O'Mullan, Cathy; Doherty, Maryanne; Coates, Rosemary; Tilley, P J Matt

    2014-01-01

    A growing body of evidence has highlighted the sexual side effects of selective serotonin reuptake inhibitor (SSRI) medication. Whilst most of the research has focused on the prevalence and treatment of sexual difficulties, little is known about how patients cope with the SSRI-related sexual side effects. The objective of this study was to explore women's experiences of coping with the sexual side effects of SSRI medication and interpretative phenomenological analysis was employed for an in-depth exploratory study of a sample of 10 women. Four broad themes emerged which are discussed under the following headings: searching, suffering in silence, trying to resolve and accepting what is. The themes provide an insight into the different strategies used by women to cope with the sexual side effects of SSRI medication and highlight the importance of contextualising these difficulties as part of an overall approach to improve the management and treatment of SSRI-related sexual side effects.

  11. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

    Directory of Open Access Journals (Sweden)

    Li-Li Wu

    2016-01-01

    Full Text Available The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA and water-EtOH soluble fraction (Fraction B, FB prepared from the Danzhi-xiaoyao-san (DZXYS by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  12. Comparative Effectiveness of Antidepressant Medication versus Psychological Intervention on Depression Symptoms in Women with Infertility and Sexual Dysfunction

    Directory of Open Access Journals (Sweden)

    Hajar Pasha

    2018-01-01

    Full Text Available Background Fertility loss is considered as a challenging experience. This study was conducted to compare the effectiveness of antidepressant medication and psychological intervention on depression symptoms in women with infertility and sexual dysfunctions (SD. Materials and Methods This randomized, controlled clinical trial study was completed from December 2014 to June 2015 in Babol, Iran. Of the 485 participants, 93 were randomly assigned in a 1:1:1 ratio to psychosexual therapy (PST, bupropion extended-release (BUP ER at a dose of 150 mg/d, and control (no intervention groups. The Beck Depression Inventory (BDI was completed at the beginning and end of the study. Duration of study was eight weeks. Statistical analyses were performed by using paired-test and analysis of covariance. Results The mean depression score on the BDI was 22.35 ± 8.70 in all participants. Mean BDI score decreased significantly in both treatment groups (PST: P<0.0001, BUP: P<0.002 from baseline to end of the study, whereas intra-individual changes in BDI score were not significant in the control group. The decrease in mean BDI score was greater with PST compared to BUP treatment (P<0.005 and the control group (P<0.0001. The PST group showed greater improvement in depression levels (severe to moderate, moderate to mild in comparison with the two other groups (P<0.001. Drug treatment was well tolerated by the participants in the BUP group. Conclusion PST can be a reliable alternative to BUP ER for relieving depression symptoms in an Iranian population of women with infertility and SD (Registration number: IRCT2015042721955N2.

  13. Antidepressant effects of standardized extract of Commiphora mukul Engl. in olfactory bulbectomized rats

    Directory of Open Access Journals (Sweden)

    Padmaja Bhimashankar Kalshetti

    2015-02-01

    Full Text Available The objective of this work was to evaluate the effects of standardized hydroalcholic extract of Commiphora mukul (HECM in animal model of chronic stress medicated depression, namely olfactory bulbectomy (OBX model in rats. Effects of 14-day (subacute oral pretreatment of HECM (50, 100 and 200 mg/kg were evaluated on depression and stress related parameters on OBX rats. Separate groups for sham control, OBX control and positive controls namely imipramine (20 mg/kg, fluoxetine (30 mg/kg and desipramine (15 mg/kg were also maintained. Behavioral and physiological parameters in open field and elevated plus maze were recorded. HECM showed dose-dependent reversal of OBX-induced physiological effects such as reduction of body weight, body temperature, heart rate and serum sodium concentration. HECM also showed reversal effects on OBX induced food intake increase and hyperactivity in open field and elevated plus maze paradigm. In conclusion, HECM demonstrated restorative effects in OBX induced depression model in rats probably due to stress reliving mechanisms.

  14. Sleep deprivation in bright and dim light : antidepressant effects on major depressive disorder

    NARCIS (Netherlands)

    Burg, W. van den; Bouhuys, A.L.; Hoofdakker, R.H. van den; Beersma, D.G.M.

    Twenty-three patients with a major depressive disorder were deprived of a night’s sleep twice weekly, one week staying up in the dimly lit living room of the ward (< 60 lux), and one week in a brightly lit room (> 2000 lux). Immediate, but transient beneficial effects of sleep deprivation were

  15. Anti-depressant effect of Paeonia lactiflora Pall extract in rats | Yu ...

    African Journals Online (AJOL)

    Neither PLPE nor fluoxetine, at the doses tested, produced significant effects on locomotor activity. Conclusion: The results suggest that Paeonia lactiflora Pall is a potential agent for the treatment of depression in humans. Keywords: Paeonia lactiflora, Depression, Tail suspension test, Forced swimming test ...

  16. Antiepileptic, behavioral, and antidepressant effects of adjuvant lamotrigine therapy in drug-resistant epilepsy

    Directory of Open Access Journals (Sweden)

    Martinović Žarko J.

    2004-01-01

    Full Text Available Aim. To evaluate the behavioral effects of lamotrigine as add-on therapy in treatment-resistant epilepsy. Methods. An open, prospective, long-term study of lamotrigine as adjuvant therapy was performed in 56 patients with drug-resistant epilepsy (female/male ratio 35/21, age range 16-51 years. All the patients kept seizure diaries, and electroencephalograms were recorded at baseline and during 24 months of the treatment. Quality of life questionnaire, Hamilton depression scale (HMD, Beck depression scale (BDI, and Hamilton anxiety scale (HMA were used before and during lamotrigine therapy. Comparative assessments were made in an age- and sex-matched control group treated with other antiepileptic drugs. Results. Overall, seizure control was improved in 55.3% of the patients, remained unchanged in 39.3%, and deteriorated in 5.4%. Improvement in some quality of life measures occurred in 50% of the patients. The HMD subscales and BDI scale showed significant improvement in lamotrigine treated patients compared to the control group (ANOVA, p < 0.01. Negative behavioral effects occurred in 10.7% of the patients. Conclusion. Lamotrigine demonstrated significant antiepileptic long-term efficacy, and its positive effects on the mood and quality of life, which surpassed the negative behavioral effects, and contributed highly to the favorable treatment outcome.

  17. Effects of antidepressant drugs on the activity of cytochrome P-450 measured by caffeine oxidation in rat liver microsomes.

    Science.gov (United States)

    Danie, W A; Syrek, M; Ryłko, Z; Wójcikowski, J

    2001-01-01

    Caffeine is a marker drug for testing the activity of CYP1A2 (3-N-demethylation) in humans and rats. Moreover, it is also a relatively specific substrate of CYP3A (8-hydroxylation). In the case of 1-N- and in particular 7-N-demethylation of caffeine, apart from CYP1A2, other cytochrome P-450 isoenzymes play a considerable role. The aim of the present study was to investigate the influence of imipramine, amitriptyline and fluoxetine on cytochrome P-450 activity measured by caffeine oxidation in rat liver microsomes. The obtained results showed that imipramine exerted a most potent inhibitory effect on caffeine metabolism. Imipramine decreased the rate of 3-N-, 1-N- and 7-N-demethylations, and 8-hydroxylation of caffeine, the effect on 3-N-demethylation being most pronounced (Ki = 33 microM). Amitriptyline showed distinct inhibition of 3-N- and 1-N-demethylation of caffeine, though its effect was less potent than in the case of imipramine (Ki = 57 and 61 pM, respectively). The influence of amitriptyline on 8-hydroxylation and especially on 7-N-demethylation of caffeine was weaker (Ki = 108 and 190 pM, respectively) than on 3-N- or 1-N-demethylation, suggesting a narrower spectrum of cytochrome P-450 inhibition by amitriptyline than by imipramine, involving mainly the subfamily CYP1A2, and--to a lesser degree--CYP3A. In contrast to the tested tricyclic antidepressants, fluoxetine did not exert any considerable effect on the 3-N- or 1-N-demethylation of caffeine (Ki = 152 and 196 microM, respectively), which indicates its low affinity for CYP1A2. However, fluoxetine displayed a clear inhibitory effect on caffeine 7-N-demethylation (Ki = 72 microM), the reaction which is catalyzed mainly by other than CYP1A2 isoenzymes. Fluoxetine diminished markedly the 8-hydroxylation of the marker drug; as reflected by Ki values, the potency of inhibition of rat CYP3A by fluoxetine was similar to that of imipramine (Ki = 40 and 45 microM, respectively). In summary, CYP1A2 was

  18. Therapeutic alliance in antidepressant treatment: cause or effect of symptomatic levels?

    Science.gov (United States)

    Zilcha-Mano, Sigal; Roose, Steven P; Barber, Jacques P; Rutherford, Bret R

    2015-01-01

    Previous studies have shown that in psychotherapy alliance is a predictor of symptomatic change, even while accounting for the temporal precedence between alliance and symptoms. However, the extent to which alliance predicts outcomes in psychopharmacology is yet to be fully investigated considering the fact that alliance can be the result, rather than the cause, of symptomatic change. The current prospective study examined whether the alliance predicts outcomes in psychopharmacology, while controlling for previous symptomatic change throughout the course of treatment. Data from a psychopharmacological randomized controlled trial for the treatment of adult major depression (n = 42), including the patients' rating of the alliance with the physicians, were analyzed. Multilevel models controlling for autoregressive lag of the dependent variable were used in all analyses to examine the effect of alliance on outcome. The effect of alliance on outcome, while controlling for prior symptomatic levels, was significant and restricted to the middle phase of treatment (week 4, p = 0.005), when most of the reductions in symptoms were observed. Exploratory analyses of the differences between placebo and medication conditions suggest that the differences between the patients in their average alliance levels predicted a greater reduction in symptoms in the placebo compared to the medication conditions (p = 0.008). The main limitation is the small cohort size. The findings suggest an effect of alliance on outcome in psychopharmacology, which is not merely the result of previous symptomatic levels. This effect may be more robust in conditions that do not include active treatment (placebo), possibly serving as a compensatory effect.

  19. Combined α7 nicotinic acetylcholine receptor agonism and partial serotonin transporter inhibition produce antidepressant-like effects in the mouse forced swim and tail suspension tests

    DEFF Research Database (Denmark)

    Andreasen, Jesper T; Redrobe, John P; Nielsen, Elsebet Ø

    2012-01-01

    Emerging evidence points to an involvement of nicotinic acetylcholine receptors (nAChRs) in major depression. Nicotine improves symptoms of depression in humans and shows antidepressant-like effects in rodents. Monoamine release is facilitated by nAChR stimulation, and nicotine-evoked serotonin (5...... represents a compound displaying the synergistic effect of α7 nAChR agonism combined with partial 5-HT reuptake inhibition previously described. The addition of α7 nAChR agonism to classical monoamine-based mechanisms may represent a novel option for the improved treatment of major depression....

  20. Synergistic antidepressant-like effects between a kappa opioid antagonist (LY2444296) and a delta opioid agonist (ADL5859) in the mouse forced swim test.

    Science.gov (United States)

    Huang, Peng; Tunis, Julia; Parry, Christopher; Tallarida, Ronald; Liu-Chen, Lee-Yuan

    2016-06-15

    Kappa opioid (KOP) receptor antagonists and delta opioid (DOP) receptor agonists have antidepressant-like effects in animal tests and may be useful for treatment-resistant depression in humans. In this study, we examined whether the combination of a KOP receptor antagonist and a DOP receptor agonist would produce a better than additive effect (i.e. synergy). LY2444296 is a short-acting selective nonpeptide KOP receptor antagonist. ADL5859 is a selective nonpeptide DOP receptor agonist which does not produce seizures and EEG disturbances. Each compound and combinations of the two were examined in the forced swim test (FST) one h post injection, a screening test for antidepressant-like effect, in male adult C57BL/6J mice (Jackson Lab). LY2444296 [subcutaneous (s.c.) injection] at 10 and 30mg/kg, but not 3mg/kg, significantly decreased immobility time in a dose-dependent manner. Intraperitoneal (i.p.) injections of ADL5859 also reduced immobility time dose-dependently at doses of 3 and 10mg/kg, but not at 1mg/kg. An analysis was conducted using the method of Tallarida and Raffa (2010), which employed dose equivalence. The relative potency of the drugs was determined to be LY2444296: ADL5859=1:0.28, which was the dose ratio for combination studies. Six combinations of the two compounds were tested in mice at a fixed dose ratio. We found that LY2444296 and ADL5859 yielded significant synergistic effects for the antidepressant-like effect at the combined dose ranging from 3.84mg/kg to 9.0mg/kg. ADL5859 (10mg/kg), LY2444296 (30mg/kg) and their combined dose (3.84mg/kg) had no effects on locomotor activities. Since the two drugs have distinct pharmacological profiles, such a synergism will allow use of lower doses of both drugs to achieve desired antidepressant effects with fewer side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Differential effects of perinatal exposure to antidepressants on learning and memory, acoustic startle, anxiety, and open-field activity in Sprague-Dawley rats.

    Science.gov (United States)

    Sprowles, Jenna L N; Hufgard, Jillian R; Gutierrez, Arnold; Bailey, Rebecca A; Jablonski, Sarah A; Williams, Michael T; Vorhees, Charles V

    2017-10-01

    Most antidepressants inhibit monoamine reuptake. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) act on the 5-HT transporter (SERT) whereas norepinephrine-dopamine reuptake inhibitors (NDRIs) act on the norepinephrine and dopamine transporters. Epidemiological reports link SSRI use during pregnancy to an increased prevalence of autism spectrum disorder (ASD). We previously showed that perinatal exposure to the SSRI citalopram (CIT) results in rodent offspring that exhibit a number of behaviors consistent with an ASD-like phenotype. The present study examined the effect of perinatal exposure to CIT (at a lower dose), another SSRI, fluoxetine (FLX), and an NDRI, bupropion (BUP). Gravid Sprague-Dawley rats were subcutaneously injected twice per day (6h apart) with 5mg/kg CIT, 5mg/kg FLX, 15mg/kg BUP, or saline (SAL) from embryonic day (E) 6-21, and directly to the pups from postnatal day (P) 1-20. As adults, one male/female from each litter was given one of a series of tests. Both SSRI-exposed groups showed spatial learning deficits in Morris and radial water mazes, increased marble burying, increased acoustic startle, hypoactivity, and attenuated activity to the stimulating effect of the NMDA-R antagonist MK-801. The BUP-exposed group showed a reduction in elevated zero-maze quadrant entries and increased stimulated open-field activity following (+)-amphetamine challenge. These results reinforce concern about the use of antidepressants during pregnancy and highlight how the two classes of drugs produce different constellations of effects with more effects associated with the SSRIs. Further investigation into how antidepressants alter brain development leading to enduring adverse neurobehavioral effects is warranted. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  2. Amphetamine and antidepressant drug effects on GABA- and NMDA-related seizures.

    Science.gov (United States)

    Borowski, T B; Kirkby, R D; Kokkinidis, L

    1993-01-01

    Research has shown a synergistic relationship between amphetamine sensitization and limbic system kindling. To explore the role of GABA and NMDA receptor activity in modulating the positive effects of amphetamine on epileptogenesis, alterations in GABA- and NMDA-related convulsions were examined after acute and chronic amphetamine administration. A single injection of d-amphetamine (7.5 mg/kg) significantly decreased latencies to generalized motor seizures induced 12 h later by the noncompetitive GABAA receptor antagonist picrotoxin (10 mg/kg). The increased sensitivity to clonus was specific to acute amphetamine treatment and was not evident following withdrawal from chronic drug exposure. Seizures induced by NMDLA (1,000 mg/kg), on the other hand, were not modified by acute amphetamine injection; however, the latency to clonus was reduced substantially after NMDLA injection to mice chronically preexposed to amphetamine. The short- and long-term amphetamine effects on GABA- and NMDA-associated convulsive activity were not paralleled by similar drug treatment schedules involving acute (20 mg/kg) and chronic administration of desipramine, zimelidine, and buproprion. These results suggest that amphetamine may be acting on inhibitory and excitatory amino acid systems independently of its monoaminergic properties. The implications of these findings were discussed in relation to amphetamine sensitization of mesolimbic functioning.

  3. Antidepressant-like effect of Kyllinga brevifolia rhizomes in male mice and chemical characterization of the components of the active ethyl acetate fraction.

    Science.gov (United States)

    Hellión-Ibarrola, M C; Montalbetti, Y; Heinichen, O Y; Kennedy, M L; Campuzano, M A; Alvarenga, N; Ibarrola, D A

    2016-12-24

    Kyllinga brevifolia rhizomes (Cyperaceae) are used in Paraguayan traditional medicine as a refreshing beverage, and is claimed to own digestive, diuretic, sedative, tonic, antispasmodic and sudorific properties. We have previously reported that its hydro- ethanolic rhizome extract possess sedative, anxiolytic and anti-aggressive-like effects in mice. However, information on its potential for treatment of syndromes associated with mood disorders is scarce. The purpose of this study is to characterize the putative antidepressant-like effects of the hydro-ethanolic extract (CEKb) and the ethyl acetate fraction (KbF-ethyl-ac) obtained from the rhizome of K. brevifolia (Rottb) on male mice exposed to forced swimming test. Also, chemical characterization of the components of the active ethyl acetate fraction was described. The antidepressant-like effects of CEKb and KbF-ethyl-ac were measured using the forced swimming test (FST) performance of male mice in single (acute), short-term and chronic modalities. Treatments in all modalities were made 1h before swimming test. The KbF-ethyl-ac was analyzed by LC-DAD-ESI-MS and LC-ESI-MS/MS in order to identify the active components. A single doses (1.0, 10.0 and 100.0mg/kg, p.o; pethyl-ac in male mice, a significant reduction of the immobility time were provoked. Likewise, short-term treatment (7 days) with 1.0, and 10.0mg/kg (pethyl-ac in male mice, a statistically significant reduction of the immobility time, were observed. Imipramine 32mg/kg/days, i.p, induced a statistically significant reduction of immobility time and was used as positive control to validate the method employed. Moreover, it was noted important differences in the onset of the antidepressant-like effect in the FST, depending on the modality of treatment with CEKb or KbF-ethyl-ac (acute, short-term or chronic). Both, efficacy and potency were higher when repeated administration of CEKb was used, and surprisingly the efficacy of 1.0mg/kg of KbF-ethyl-ac (14

  4. The role of patient expectancy in placebo and nocebo effects in antidepressant trials.

    Science.gov (United States)

    Rutherford, Bret R; Wall, Melanie M; Glass, Andrew; Stewart, Jonathan W

    2014-10-01

    To determine whether patient expectancy plays a role in observed placebo and nocebo effects in 2 clinical trials. Data were reanalyzed from 2 fluoxetine-discontinuation studies conducted from March 1990 to September 1992 and from May 1997 to December 2002. The 673 outpatients included were aged 18-65 years with DSM-III-R major depressive disorder (MDD), responded to 12-week duration open treatment, and were randomized to continued fluoxetine or placebo for an additional year. Participants in 1 of the included studies received a fixed dose of fluoxetine 20 mg daily, while the second study utilized flexible fluoxetine doses up to 60 mg daily. Mixed effects longitudinal models determined whether the possible randomization to placebo at 12 weeks resulted in significant depressive symptom worsening across treatments. Correlations were computed between early symptom change (weeks 1-3 of open treatment) and postrandomization symptom change (weeks 13-16 following randomization). Participants continuing to receive fluoxetine and those switched to placebo had significantly higher mean Hamilton Depression Rating Scale (HDRS) scores immediately postrandomization compared to the final weeks of open treatment (P placebo-treated patients). In both studies, early HDRS change was significantly correlated with postrandomization HDRS change for patients receiving fluoxetine (r = -0.46, P placebo (r = -0.48, P placebo following 12 weeks of open fluoxetine was associated with significant symptom worsening in 2 large fluoxetine discontinuation studies. Worsening depression scores following randomization were significantly associated with the degree of improvement participants experienced during weeks 1-3 of open treatment. These results suggest that treatment changes influence patients' expectations of improvement, which, in turn, affect their depressive symptoms. © Copyright 2014 Physicians Postgraduate Press, Inc.

  5. Pharmacogenetics of antidepressants

    Directory of Open Access Journals (Sweden)

    Concetta eCrisafulli

    2011-02-01

    Full Text Available Up to 60% of depressed patients do not respond completely to antidepressants (AD and up to 30% do not respond at all. Genetic factors contribute for about 50% of the AD response. During the recent years the possible influence of a set of candidate genes as genetic predictors of AD response efficacy was investigated by us and others. They include the cytochrome P450 (CYP superfamily, the P-glycoprotein (ABCB1, the tryptophan hydroxylase (TPH, the catechol-O-methyltransferase (COMT, the monoamine oxidase A (MAOA, the serotonin transporter (5-HTTLPR, the norepinephrine transporter (NET, the dopamine transporter (DAT, variants in the 5HT1A, 2A , 3A, 3B and 6 receptors, adrenoreceptor beta-1 (ADRB1 and alpha-2 (ADRA2A, the dopamine receptors (D2, the G-protein beta3-subunit (GNB3, the corticotropin releasing hormone (CRH receptors (CRHR1 and CRHR2, the glucocorticoid receptors (GR, the c-AMP response-element binding (CREB and the brain-derived neurotrophic factor (BDNF. Marginal associations were reported for angiotensin I converting enzyme (ACE, circadian locomoter output cycles kaput protein (CLOCK, glutamatergic system, nitric oxide synthase (NOS and interleukin 1-beta (IL-1beta gene. In conclusion, gene variants seem to influence human behavior, liability to disorders and treatment response. Nonetheless, gene x enviroment interactions have been hypothesized to modulate several of these effects.

  6. Modulation of Neurogenesis through the Promotion of Energy Production Activity Is behind the Antidepressant-Like Effect of Colonial Green Alga, Botryococcus braunii.

    Science.gov (United States)

    Sasaki, Kazunori; Othman, Mahmoud B; Demura, Mikihide; Watanabe, Makoto; Isoda, Hiroko

    2017-01-01

    Algae have been recognized as important resources providing functional components due to their capacity to exert beneficial effects on health. Therefore, there is increasing interest in investigating the biological activity of algae. In this study, we evaluated the antidepressant-like effect of the administration of 100 mg/kg/day of the ethanol extract of colonial green alga Botryococcus braunii (EEB) for 14 consecutive days in the forced swimming test (FST)-induced depression in imprinting control region (ICR) mice. Imipramine, a commercial antidepressant drug, was used as a positive control. In addition, we investigated the molecular mechanisms underlying the effect of EEB by measuring ATP production and by assessing any change in gene expression at the end of the treatment using real-time polymerase chain reaction (PCR) and microarray assays. We showed that the immobility time in the water-administered control (FST stress) group gradually increased from day 1 to day 14. However, treatment with EEB caused a significant decrease of immobility time in the FST compared with that in the FST stress group. Microarray and real-time PCR results revealed that EEB treatment induced variation in the expression of several genes associated with neurogenesis, energy metabolism, and dopamine synthesis. Interestingly, we revealed that only EEB treatment enhanced the promotion of energy production, while treatment with imipramine was ineffective. Our study provides the first evidence that B. braunii enhances energy production, which may contribute to the modulation of neurogenesis and to the enhancement of dopaminergic function, in turn potentially underlying the antistress- and antidepressant-like effects that we observed.

  7. Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system.

    Science.gov (United States)

    Machado, Daniele G; Kaster, Manuella P; Binfaré, Ricardo W; Dias, Munique; Santos, Adair R S; Pizzolatti, Moacir G; Brighente, Inês M C; Rodrigues, Ana Lúcia S

    2007-03-30

    Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.

  8. Dual aminergic regulation of central beta adrenoceptors. Effect of atypical antidepressants and 5-hydroxytryptophan

    Energy Technology Data Exchange (ETDEWEB)

    Manier, D.H.; Gillespie, D.D.; Sulser, F.

    1989-06-01

    Nonlinear regression analysis of agonist competition binding curves reveals that the (/sup 3/H)-dihydroalprenolol-labeled receptor population with low affinity for isoproterenol is increased by p-chlorophenylalanine (PCPA) and this increase is abolished by 5-hydroxytryptophan (5-HTP) in vivo. Desipramine (DMI) decreased the beta adrenoceptor population with high agonist affinity to the same degree in PCPA-treated animals as in control animals, thus explaining the reported discrepancy between beta adrenoceptor number and responsiveness of the beta adrenoceptor-coupled adenylate cyclase system. Mianserin also selectively reduced the beta adrenoceptor population with high agonist affinity in membrane preparations of normal animals, whereas fluoxetine selectively abolished the upregulation of the low affinity sites in reserpinized animals and had no effect on either receptor population from brain of normal animals. The results emphasize the importance of nonlinear regression analysis of agonist competition binding for the interpretation of drug action and encourage the pursuit of the molecular neurobiology of the serotonin (5-HT)/norepinephrine (NE) link in brain.

  9. A network meta-analysis comparing effects of various antidepressant classes on the Digit Symbol substitution test (DSST) as a measure of cognitive dysfunction in patients with major depressive disorder.

    Science.gov (United States)

    Baune, Bernhard T; Brignone, Mélanie; Larsen, Klaus Groes

    2017-10-19

    Major depressive disorder (MDD) is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis (NMA) were carried out to assess the relative effect of antidepressants on cognitive dysfunction in MDD. MEDLINE ®, Embase ®, Cochrane, CDSR, PsychINFO ® databases, clinical trial registries, and relevant conference abstracts were searched for randomised controlled trials (RCTs) assessing the effects of antidepressants/placebo on cognition. An NMA comparing antidepressants was conducted using a random effects model. The database search retrieved 11,337 citations of which 72 RCTs from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test (DSST), which targets multiple domains of cognition and is recognised as being sensitive to change, was the only test that was used across 12 of the included RCTs and that allowed the construction of a stable network suitable for the NMA. The interventions assessed included selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and other non-SSRI/SNRIs. The NMA using the DSST showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the DSST versus placebo (standardised mean difference: 0.325 (95% CI=[0.120; 0.529], p=0.009). When comparing to other antidepressants, Vortioxetine was statistically more efficacious on the DSST versus escitalopram, nortriptyline, and the SSRI and TCA classes. This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the DSST indicate differential effects of various antidepressants on improving cognitive function in patients with MDD.

  10. Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT₁A and 5-HT₇ Antagonists in Animal Models.

    Directory of Open Access Journals (Sweden)

    Karolina Pytka

    Full Text Available The aim of this study was to further characterize pharmacological properties of two phenylpiperazine derivatives: 1-{2-[2-(2,6-dimethlphenoxyethoxy]ethyl}-4-(2-methoxyphenylpiperazynine hydrochloride (HBK-14 and 2-[2-(2-chloro-6-methylphenoxyethoxy]ethyl-4-(2- methoxyphenylpiperazynine dihydrochloride (HBK-15 in radioligand binding and functional in vitro assays as well as in vivo models. Antidepressant-like properties were investigated in the forced swim test (FST in mice and rats. Anxiolytic-like activity was evaluated in the four-plate test in mice and elevated plus maze test (EPM in rats. Imipramine and escitalopram were used as reference drugs in the FST, and diazepam was used as a standard anxiolytic drug in animal models of anxiety. Our results indicate that HBK-14 and HBK-15 possess high or moderate affinity for serotonergic 5-HT2, adrenergic α1, and dopaminergic D2 receptors as well as being full 5-HT1A and 5-HT7 receptor antagonists. We also present their potent antidepressant-like activity (HBK-14-FST mice: 2.5 and 5 mg/kg; FST rats: 5 mg/kg and (HBK-15-FST mice: 1.25, 2.5 and 5 mg/kg; FST rats: 1.25 and 2.5 mg/kg. We show that HBK-14 (four-plate test: 2.5 and 5 mg/kg; EPM: 2.5 mg/kg and HBK-15 (four-plate test: 2.5 and 5 mg/kg; EPM: 5 mg/kg possess anxiolytic-like properties. Among the two, HBK-15 has stronger antidepressant-like properties, and HBK-14 displays greater anxiolytic-like activity. Lastly, we demonstrate the involvement of serotonergic system, particularly 5-HT1A receptor, in the antidepressant- and anxiolytic-like actions of investigated compounds.

  11. Neuromodulation by soy diets or equol: Anti-depressive & anti-obesity-like influences, age- & hormone-dependent effects

    Directory of Open Access Journals (Sweden)

    Lund Trent D

    2011-03-01

    . Conclusions Consumption of dietary isoflavones or equol exposure in rats has body weight controlling effects and equol specifically may have antidepressant potential dependent upon diet initiation and/or dosage of treatments. The current study demonstrates that equol is able to decrease body weight, abdominal WAT, and depressive-related behavior. While other factors and mechanisms may play a role, in part, the present results provide a greater understanding of how isoflavonoid molecules modulate the brain's influence on behavior.

  12. A multivariate approach linking reported side effects of clinical antidepressant and antipsychotic trials to in vitro binding affinities.

    Science.gov (United States)

    Michl, Johanna; Scharinger, Christian; Zauner, Miriam; Kasper, Siegfried; Freissmuth, Michael; Sitte, Harald H; Ecker, Gerhard F; Pezawas, Lukas

    2014-09-01

    The vast majority of approved antidepressants and antipsychotics exhibit a complex pharmacology. The mechanistic understanding of how these psychotropic medications are related to adverse drug reactions (ADRs) is crucial for the development of novel drug candidates and patient adherence. This study aims to associate in vitro assessed binding affinity profiles (39 compounds, 24 molecular drug targets) and ADRs (n=22) reported in clinical trials of antidepressants and antipsychotics (n>59.000 patients) by the use of robust multivariate statistics. Orthogonal projection to latent structures (O-PLS) regression models with reasonable predictability were found for several frequent ADRs such as nausea, diarrhea, hypotension, dizziness, headache, insomnia, sedation, sleepiness, increased sweating, and weight gain. Results of the present study support many well-known pharmacological principles such as the association of hypotension and dizziness with α1-receptor or sedation with H1-receptor antagonism. Moreover, the analyses revealed novel or hardly investigated mechanisms for common ADRs including the potential involvement of 5-HT6-antagonism in weight gain, muscarinic receptor antagonism in dizziness, or 5-HT7-antagonism in sedation. To summarize, the presented study underlines the feasibility and value of a multivariate data mining approach in psychopharmacological development of antidepressants and antipsychotics. Copyright © 2014. Published by Elsevier B.V.

  13. Antidepressant Therapy in Severe Depression May Have Different Effects on Ego-Dystonic and Ego-Syntonic Suicidal Ideation

    Directory of Open Access Journals (Sweden)

    Louise Brådvik

    2011-01-01

    Full Text Available The objective of the present study was to investigate whether ego-dystonic and ego-syntonic suicidal ideation occurred at different frequencies during antidepressant therapy. A blind evaluation has been performed on records of 100 suicides with a primary severe depression and 100 matched controls, admitted to the Department of Psychiatry, Lund, Sweden. Ego-dystonic suicidal ideation was more commonly reported during adequate treatment as compared to ego-syntonic ideation (P=.004. Men who committed suicide during adequate antidepressant therapy more often reported ego-dystonic suicidal ideation earlier in their lives compared with those who were not treated (P=.0377. This may indicate that treatment failure for ego-dystonic ideation was a precursor of their suicides. Consequently, ego-dystonic ideation seems to show a poorer response to antidepressant therapy as compared to ego-syntonic ideation, which may be more directly related to depression. Ego-dystonic ideation is proposed to be related to depressive psychosis.

  14. Curcumin as an add-on to antidepressive treatment: a randomized, double-blind, placebo-controlled, pilot clinical study.

    Science.gov (United States)

    Bergman, Joseph; Miodownik, Chanoch; Bersudsky, Yuly; Sokolik, Shmuel; Lerner, Paul P; Kreinin, Anatoly; Polakiewicz, Jacob; Lerner, Vladimir

    2013-01-01

    Depression is a widespread mental disorder in which nearly half of the affected people have recurrent symptoms. Drug combinations may produce cumulative adverse effects, especially in elderly and physically ill patients. It was demonstrated that curcumin possesses antidepressive activity in various animal models of depression, and a combination of curcumin with some antidepressants potentiates the antidepressive effect of these agents. We sought to evaluate the efficacy of curcumin as an antidepressive agent in a combination with other antidepressants in patients with major depression. Forty patients with a first episode of depression participated in a 5-week, double-blind, randomized, placebo-controlled study. The subjects were treated with either 500-mg/d curcumin or placebo together with antidepressants (escitalopram or venlafaxine) during August 2010 until June 2011. The outcome measures were Clinical Global Impression-Severity Scale, Hamilton Depression Rating Scale, and Montgomery-Asberg Depression Rating Scale. Analysis of variance showed significant positive changes in both groups from baseline to the end of the study in all scales of measurement. These changes became significant from the first visit after 7 days of treatment. There was no difference between curcumin and placebo, which means negative results. However, the patients in the curcumin group demonstrated a trend to a more rapid relief of depressive symptoms in comparison to those in the placebo group. None of the patients complained of any adverse effect during the study. Although there is no definitive proof that curcumin can induce an earlier beneficial effect of antidepressive agents, it seems like an extended study is needed to prove it, using higher therapeutic doses of curcumin.

  15. L-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters.

    Science.gov (United States)

    Xue, Jinsong; Li, Hongyan; Deng, Xueyang; Ma, Zhanqiang; Fu, Qiang; Ma, Shiping

    2015-07-01

    L-Menthone (MTN) is a Chinese old remedy extracted from the genus Mentha. It has been widely used as a cooling agent and a counterirritant for pain relief, although its antidepressant-like effects have not yet been reported. The present study was designed to investigate whether MTN confers an antidepressant-like effect in mice exposed to unpredictable chronic mild stress (UCMS) and to explore its potential mechanisms. The effects of MTN on mouse behavioral changes were investigated in our study. We determined the levels of the nucleotide binding, oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, inflammatory cytokines and neurotransmitters in the hippocampus of mice. Behavioral tests, including the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) revealed that MTN (15 and 30mg/kg) treatments for 3weeks alleviated the depression symptoms of UCMS in mice. Mice receiving MTN treatments exhibited reduced levels of NLRP3 and caspase-1. Moreover, MTN treatments reversed the UCMS-induced alterations in the concentrations of neurotransmitter norepinephrine (NE) and serotonin (5-HT) and inhibited the expression of pro-inflammatory cytokines (PIC) interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus of mice. Taken together, our findings suggested that MTN may play a potential antidepressant-like role in the UCMS mouse model by regulating the NLRP3 inflammasome and mediating inflammatory cytokines and central neurotransmitters, which together provide insight towards the development of novel therapeutic treatments for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Double blinding requirement for validity claims in cognitive-behavioral therapy intervention trials for major depressive disorder. Analysis of Hollon S,  et al., Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial

    National Research Council Canada - National Science Library

    Berger, Douglas

    2015-01-01

    .... A study by Hollon et al. published in JAMA Psychiatry that compared an antidepressant medication-only arm with a combined CBT/antidepressant arm concluded that the cognitive therapy/antidepressant combination enhanced...

  17. Escitalopram versus other antidepressive agents for depression

    Science.gov (United States)

    Cipriani, Andrea; Santilli, Claudio; Furukawa, Toshi A; Signoretti, Alessandra; Nakagawa, Atsuo; McGuire, Hugh; Churchill, Rachel; Barbui, Corrado

    2014-01-01

    Background Although pharmacological and psychological interventions are both effective for major depression, antidepressant drugs remain the mainstay of treatment in primary and secondary care settings. During the last 20 years, antidepressant prescribing has risen dramatically in western countries, mainly because of the increasing consumption of selective serotonin reuptake inhibitors (SSRIs) and newer antidepressants, which have progressively become the most commonly prescribed antidepressants. Escitalopram is the pure S-enantiomer of the racemic citalopram. Objectives To assess the evidence for the efficacy, acceptability and tolerability of escitalopram in comparison with tricyclics, other SSRIs, heterocyclics and newer agents in the acute-phase treatment of major depression. Search methods Electronic databases were searched up to July 2008. Trial databases of drug-approving agencies were hand-searched for published, unpublished and ongoing controlled trials. Selection criteria All randomised controlled trials comparing escitalopram against any other antidepressant (including non-conventional agents such as hypericum) for patients with major depressive disorder (regardless of the diagnostic criteria used). Data collection and analysis Data were entered by two review authors (double data entry). Responders and remitters to treatment were calculated on an intention-to-treat basis. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI). Continuous data were analysed using standardised mean differences (with 95% CI) using the random effects model. Main results Fourteen trials compared escitalopram with another SSRI and eight compared escitalopram with a newer antidepressive agent (venlafaxine, bupropion and duloxetine). Escitalopram was shown to be significantly more effective than citalopram in achieving acute response (OR 0.67, 95% CI 0.50 to 0.87). Escitalopram was also more effective than citalopram in terms of remission (OR

  18. Evaluation of the Effectiveness of a Psychoeducational Intervention in Treatment-Naïve Patients with Antidepressant Medication in Primary Care: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    R. Casañas

    2015-01-01

    Full Text Available Background. There is evidence supporting the effectiveness of psychoeducation (PE in patients with symptoms of depression in primary care (PC, but very few studies have assessed this intervention in antidepressant-naïve patients. The aim of this study is to assess the effectiveness of a PE program in these patients, since the use of antidepressant (AD medication may interfere with the effects of the intervention. Methods. 106 participants were included, 50 from the PE program (12 weekly 1.5-hour sessions and 56 from the control group (CG that received the usual care. Patients were assessed at baseline and at 3, 6, and 9 months. The main outcome measures were the Beck Depression Inventory (BDI and remission based on the BDI. The analysis was carried out on an intention-to-treat basis. Results. The PE program group showed remission of symptoms of 40% (P=0.001 posttreatment and 42% (P=0.012 at 6 months. The analysis only showed significant differences in the BDI score posttreatment (P=0.008; effect size Cohen’s d′=0.55. Conclusions. The PE intervention is an effective treatment in the depressive population not treated with AD medication. Before taking an AD, psychoeducational intervention should be considered.

  19. Evaluation of the Effectiveness of a Psychoeducational Intervention in Treatment-Naïve Patients with Antidepressant Medication in Primary Care: A Randomized Controlled Trial

    Science.gov (United States)

    Casañas, R.; Catalán, R.; Penadés, R.; Real, J.; Valero, S.; Muñoz, MA.; Lalucat-Jo, LL.; Casas, M.

    2015-01-01

    Background. There is evidence supporting the effectiveness of psychoeducation (PE) in patients with symptoms of depression in primary care (PC), but very few studies have assessed this intervention in antidepressant-naïve patients. The aim of this study is to assess the effectiveness of a PE program in these patients, since the use of antidepressant (AD) medication may interfere with the effects of the intervention. Methods. 106 participants were included, 50 from the PE program (12 weekly 1.5-hour sessions) and 56 from the control group (CG) that received the usual care. Patients were assessed at baseline and at 3, 6, and 9 months. The main outcome measures were the Beck Depression Inventory (BDI) and remission based on the BDI. The analysis was carried out on an intention-to-treat basis. Results. The PE program group showed remission of symptoms of 40% (P = 0.001) posttreatment and 42% (P = 0.012) at 6 months. The analysis only showed significant differences in the BDI score posttreatment (P = 0.008; effect size Cohen's d′ = 0.55). Conclusions. The PE intervention is an effective treatment in the depressive population not treated with AD medication. Before taking an AD, psychoeducational intervention should be considered. PMID:26380366

  20. Genetic predictors of antidepressant side effects: a grouped candidate gene approach in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study.

    Science.gov (United States)

    Hodgson, Karen; Uher, Rudolf; Crawford, Andrew A; Lewis, Glyn; O'Donovan, Michael C; Keers, Robert; Dernovsek, Mojca Z; Mors, Ole; Hauser, Joanna; Souery, Daniel; Maier, Wolfgang; Henigsberg, Neven; Rietschel, Marcella; Placentino, Anna; Aitchison, Katherine; Farmer, Anne; Davis, Oliver; McGuffin, Peter

    2014-02-01

    The unwanted side effects associated with antidepressants are key determinants of treatment adherence in depression; propensity to experience these adverse drug reactions (ADRs) may be influenced by genetic variation. However, previous work attempting to ascertain the genetic variants involved has had limited success, in part due to the range of ADRs reported with antidepressants. ADRs reported with antidepressant treatment were categorised using their likely pharmacological basis; adrenergic, cholinergic, serotonergic and histaminergic. To identify genetic predictors of susceptibility to each group of ADRs, a candidate gene analysis was performed with data from 431 depressed patients (from a total sample size of 811 patients) enrolled in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, who were randomly allocated to receive treatment with escitalopram or nortriptyline. Data from 474 patients treated with citalopram or reboxetine in the GenPod project (total sample of 601 patients) were used for replication of significant findings. We found no significant predictors of presumed adrenergic, cholinergic and histaminergic ADRs. Putative serotonergic ADRs were significantly associated with variation in the gene encoding the serotonin 2C receptor (HTR2C, rs6644093, odds ratio (OR)=1.72, 95% confidence interval (CI)=1.31-2.25, p=7.43×10(-5)) in GENDEP. However, this finding was not replicated in GenPod. The association between serotonergic side effects and variation in the HTR2C gene in the GENDEP sample supports the hypothesis that serotonin receptor-mediated mechanisms underlie these adverse reactions, however this finding was not replicated in GenPod.

  1. Potentials of curcumin as an antidepressant.

    Science.gov (United States)

    Kulkarni, Shrinivas; Dhir, Ashish; Akula, Kiran Kumar

    2009-11-01

    Major depression, a debilitating psychiatric disorder, is predicted to be the second most prevalent human illness by the year 2020. Various antidepressants, ranging from monoamine oxidase inhibitors to recently developed dual reuptake inhibitors, are prescribed for alleviating the symptoms of depression. Despite the availability of these blockbuster molecules, approximately 30% of depressed patients do not respond to the existing drug therapies and the remaining 70% fails to achieve complete remission. Moreover, antidepressants are associated with a plethora of side effects and drug-drug/drug-food interactions. In this context, novel approaches are being tried to find more efficacious and safer drugs for the treatment of major depression. Curcumin is one such molecule that has shown promising efficacy in various animal models of major depression. Although the mechanism of the antidepressant effect of curcumin is not fully understood, it is hypothesized to act through inhibiting the monoamine oxidase enzyme and modulating the release of serotonin and dopamine. Moreover, evidences have shown that curcumin enhances neurogenesis, notably in the frontal cortex and hippocampal regions of the brain. The use of curcumin in clinics for the treatment of major depression is limited due to its poor gastrointestinal absorption. The present review attempts to discuss the pharmacological profile along with molecular mechanisms of the antidepressant effect of curcumin in animal models of depression. A need for clinical trials in order to explore the antidepressant efficacy and safety profile of curcumin is emphasized.

  2. Potentials of Curcumin as an Antidepressant

    Directory of Open Access Journals (Sweden)

    S.K. Kulkarni

    2009-01-01

    Full Text Available Major depression, a debilitating psychiatric disorder, is predicted to be the second most prevalent human illness by the year 2020. Various antidepressants, ranging from monoamine oxidase inhibitors to recently developed dual reuptake inhibitors, are prescribed for alleviating the symptoms of depression. Despite the availability of these blockbuster molecules, approximately 30% of depressed patients do not respond to the existing drug therapies and the remaining 70% fails to achieve complete remission. Moreover, antidepressants are associated with a plethora of side effects and drug-drug/drug-food interactions. In this context, novel approaches are being tried to find more efficacious and safer drugs for the treatment of major depression. Curcumin is one such molecule that has shown promising efficacy in various animal models of major depression. Although the mechanism of the antidepressant effect of curcumin is not fully understood, it is hypothesized to act through inhibiting the monoamine oxidase enzyme and modulating the release of serotonin and dopamine. Moreover, evidences have shown that curcumin enhances neurogenesis, notably in the frontal cortex and hippocampal regions of the brain. The use of curcumin in clinics for the treatment of major depression is limited due to its poor gastrointestinal absorption. The present review attempts to discuss the pharmacological profile along with molecular mechanisms of the antidepressant effect of curcumin in animal models of depression. A need for clinical trials in order to explore the antidepressant efficacy and safety profile of curcumin is emphasized.

  3. Investigation of the Anxiolytic and Antidepressant Effects of Curcumin, a Compound From Turmeric (Curcuma longa), in the Adult Male Sprague-Dawley Rat.

    Science.gov (United States)

    Ceremuga, Tomás Eduardo; Helmrick, Katie; Kufahl, Zachary; Kelley, Jesse; Keller, Brian; Philippe, Fabiola; Golder, James; Padrón, Gina

    As the use of herbal medications continues to increase in America, the potential interaction between herbal and prescription medications necessitates the discovery of their mechanisms of action. The purpose of this study was to investigate the anxiolytic and antidepressant effects of curcumin, a compound from turmeric (Curcuma longa), and its effects on the benzodiazepine site of the γ-aminobutyric acid receptor A (GABAA) receptor. Utilizing a prospective, between-subjects group design, 55 male Sprague-Dawley rats were randomly assigned to 1 of the 5 intraperitoneally injected treatment groups: vehicle, curcumin, curcumin + flumazenil, midazolam, and midazolam + curcumin. Behavioral testing was performed using the elevated plus maze, open field test, and forced swim test. A 2-tailed multivariate analysis of variance and least significant difference post hoc tests were used for data analysis. In our models, curcumin did not demonstrate anxiolytic effects or changes in behavioral despair. An interaction of curcumin at the benzodiazepine site of the GABAA receptor was also not observed. Additional studies are recommended that examine the anxiolytic and antidepressant effects of curcumin through alternate dosing regimens, modulation of other subunits on the GABAA receptor, and interactions with other central nervous system neurotransmitter systems.

  4. High-Speed Imaging Reveals Opposing Effects of Chronic Stress and Antidepressants on Neuronal Activity Propagation through the Hippocampal Trisynaptic Circuit

    Directory of Open Access Journals (Sweden)

    Jens eStepan

    2015-11-01

    Full Text Available Antidepressants (ADs are used as first-line treatment for most stress-related psychiatric disorders. The alterations in brain circuit dynamics that can arise from stress exposure and underlie therapeutic actions of ADs remain, however, poorly understood. Here, enabled by a recently developed voltage-sensitive dye imaging assay in mouse brain slices, we examined the impact of chronic stress and concentration-dependent effects of eight clinically used ADs (belonging to different chemical/functional classes on evoked neuronal activity propagations through the hippocampal trisynaptic circuitry (HTC: perforant path - dentate gyrus - area CA3 - area CA1. Exposure of mice to chronic social defeat stress led to markedly weakened activity propagations (HTC-Waves. In contrast, at concentrations in the low micromolar range, all ADs, which were bath applied to slices, caused an amplification of HTC-Waves in CA regions (invariably in area CA1. The fast-acting antidepressant ketamine, the mood stabilizer lithium, and brain-derived neurotrophic factor (BDNF exerted comparable enhancing effects, whereas the antipsychotic haloperidol and the anxiolytic diazepam attenuated HTC-Waves. Collectively, we provide direct experimental evidence that chronic stress can depress neuronal signal flow through the HTC and demonstrate shared opposing effects of ADs. Thus, our study points to a circuit-level mechanism of ADs to counteract stress-induced impairment of hippocampal network function. However, the observed effects of ADs are impossible to depend on enhanced neurogenesis.

  5. The Antidepressant Effect of Angelica sinensis Extracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Jun Shen

    2016-01-01

    Full Text Available Angelica sinensis (AS, a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS- induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF and the phosphorylation of cAMP-response element binding protein (CREB and extracellular signal-regulated protein kinase (ERK 1/2 were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB were upregulated in the hippocampus.

  6. Rapid activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway by electroconvulsive shock in the rat prefrontal cortex is not associated with TrkB neurotrophin receptor activation

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Rantamäki, Tomi P J; Larsen, Marianne Hald

    2007-01-01

    , are important pathways triggered by TrkB autophosphorylation. 2. We have previously observed that chemical antidepressants induce a rapid activation of TrkB signaling in the rodent prefrontal cortex (PFC), which is likely a consequence of the stimulatory effect of antidepressants on BDNF synthesis. However...

  7. The role of nitrergic system in antidepressant effects of acute administration of zinc, magnesium and thiamine on progesterone induced postpartum depression in mice

    Directory of Open Access Journals (Sweden)

    Nikseresht S

    2010-08-01

    Full Text Available "nBackground: Postpartum depression is a mood disorder that has harmful effects on mothers, infants, family and relationships. Acute decrease of progesterone after delivery has been proposed as a cause for postpartum depression. This hormone can affect neurotransmitters' function. Zinc (Zn and magnesium (Mg as trace elements exert their antidepressant effects through neurotransmitter pathways. On the other hand, thiamin (Vit B1 deficiency leads to depression in animal models. The aim of this study was to evaluate effects of combination of zinc, magnesium and thiamine on postpartum depression and role of nitrergic system. "n"nMethods: One hundred ten female mice in five groups were used. Postpartum depression was conducted using progesterone injections. Combinations of Zinc chloride, magnesium chloride and thiamine HCL were administered 30 minutes before open field and forced swimming test (FST. In order to investigate role of nitrergic system, L-arginine and LNAME were administered. "n"nResults: All treatment groups spent less immobility time than the control group (p< 0.05. Combined administration of Zn+ Mg+ Vit B1 caused the most reduction in immobility time. Administration of L-NAME in Zn+ Mg+ Vit B1 group caused reduction in immobility time while administration of L-arginine caused increase in immobility time in the same group. "nConclusion: Zinc, magnesium and thiamine can improve depressive symptoms by nitrergic pathway. These elements as supplement compounds could be alternatives for antidepressants in postpartum period.

  8. Involvement of Normalized Glial Fibrillary Acidic Protein Expression in the Hippocampi in Antidepressant-Like Effects of Xiaoyaosan on Chronically Stressed Mice

    Directory of Open Access Journals (Sweden)

    Xiu-Fang Ding

    2017-01-01

    Full Text Available The research has only yielded a partial comprehension of MDD and the mechanisms underlying the antidepressant-like effects of XYS. Therefore, in this study, we aimed to explore the effects of XYS on chronic unpredictable mild stress- (CUMS- induced changes in the neuronal and the astrocytic markers in the mouse hippocampus. The physical states and depressive-like behaviors in mice with CUMS were recorded. The serum contents of brain-derived neurotrophic factor (BDNF and glial cell line-derived neurotrophic factor (GDNF were measured. The protein and mRNA expressions and the immunoreactivities of glial fibrillary acidic protein (GFAP and neuronal nuclei (NeuN in mouse hippocampus were detected using a Western blot, qRT-PCR, and immunohistochemical staining, respectively. XYS treatment markedly improved the physical state and depressive-like behaviors in mice subjected to CUMS compared with the model group, and the serum contents of BDNF and GDNF were significantly upregulated. XYS treatment also elevated the protein and mRNA levels, as well as the immunoreactivity of GFAP in the hippocampus. However, CUMS did not influence NeuN expression. In conclusion, these results reveal that chronic administration of XYS elicits antidepressant-like effects in a mouse model of depression and may normalize glial fibrillary acidic protein expression in the hippocampi of mice with CUMS.

  9. Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang; Jin, Wenwen

    2014-05-01

    Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain.

  10. Antidepressant effects of curcumin and HU-211 coencapsulated solid lipid nanoparticles against corticosterone-induced cellular and animal models of major depression.

    Science.gov (United States)

    He, Xiaolie; Zhu, Yanjing; Wang, Mei; Jing, Guoxin; Zhu, Rongrong; Wang, Shilong

    Major depression is a complex neuropsychiatric disorder with few treatment approaches. The use of nontargeted antidepressants induced many side effects with their low efficacy. A more precise targeting strategy is to develop nanotechnology-based drug delivery systems; hence, we employed solid lipid nanoparticles (SLNs) to encapsulate HU-211 and curcumin (Cur). The antidepressant effects of the dual-drug nanoparticles (Cur/SLNs-HU-211) for major depression treatment were investigated in corticosterone-induced cellular and animal models of major depression. Cur/SLNs-HU-211 can effectively protect PC12 cells from corticosterone-induced apoptosis and can release more dopamine, which may be associated with the higher uptake of Cur/SLNs-HU-211 shown by cellular uptake behavior analysis. Additionally, Cur/SLNs-HU-211 significantly reduced the immobility time in forced swim test, enhanced fall latency in rotarod test, and improved the level of dopamine in mice blood. Cur/SLNs-HU-211 can deliver more Cur to the brain and thus produce a significant increase in neurotransmitters level in brain tissue, especially in the hippocampus and striatum. The results of Western blot and immunofluorescence revealed that Cur/SLNs-HU-211 can significantly enhance the expression of CB1, p-MEK1, and p-ERK1/2. Our study suggests that Cur/SLNs-HU-211 may have great potential for major depression treatment.

  11. Involvement of the Cerebral Monoamine Neurotransmitters System in Antidepressant-Like Effects of a Chinese Herbal Decoction, Baihe Dihuang Tang, in Mice Model

    Directory of Open Access Journals (Sweden)

    Meng-Li Chen

    2012-01-01

    Full Text Available Baihe Dihuang Tang (BDT is a renowned Chinese herbal formula which is commonly used for treating patients with mental instability, absentmindedness, insomnia, deficient dysphoria, and other psychological diseases. These major symptoms closely associated with the depressive disorders. BDT was widely popular use for treating emotion-thought disorders for many years in China. In the present study, the antidepressant-like effect of BDT in mice was investigated by using the forced swim test (FST and the tail suspension test (TST. The underlying mechanism was explored by determining the effect of BDT on the level of cerebral monoamine neurotransmitters. BDT (9 and 18 g/kg, p.o. for 14 days administration significantly reduced the immobility time in both the FST and the TST without changing locomotion in the open field-test (OFT. Moreover, BDT treatment at the dose of 18 g/kg inhibited reserpine-induced ptosis. Meanwhile, BDT enhanced 5-HT and NA levels in mouse cerebrum as well as decreased the ratio of 5-HT compared to its metabolite, 5-HIAA, (turnover, 5-HIAA/5-HT after TST. The results demonstrated that the antidepressant-like effect of BDT is mediated, at least partially, via the central monoaminergic neurotransmitter system.

  12. Adherence to antidepressants

    Directory of Open Access Journals (Sweden)

    Abimbola Farinde

    2013-01-01

    Full Text Available While major depression is considered a frequent mental illness there are ongoing reports of high non-adherence to antidepressant medications which places suffers at high risk for relapse, recurrence, or greater impairment,. The World Health Organization (WHO defines adherence as the extent to which a person′s behavior (e.g. taking medications can align with the agreed recommendations of a health care provider. Unfortunately while patient may recognize the importance of adherence to antidepressant medications the majority of patients do not adhere to their prescribed antidepressants. Some of the factors that may contribute to or lead to non-adherence include knowingly or unknowingly missing doses, taking extra doses, delaying administration times, or taking drug holidays. Pharmacists have the unique ability to deter non-adherence through the performance of continuous assessment and monitoring of adherence in this population given these accessibility. Additionally, pharmacists are able to develop therapeutic alliances with patients that can help to increase the likelihood of achieving positive patient outcomes. Antidepressant non-adherence can be viewed as a significant public health concern so it is important for patients to be educated about the importance of adherence, and health care professionals should be aware of factors or patient characteristics that can serve as barriers to non-adherence.

  13. Factors associated with the prescription of antidepressive medication to breast cancer patients

    DEFF Research Database (Denmark)

    Suppli, Nis P; Deltour, Isabelle; Damkjaer, Lars H

    2011-01-01

    We evaluated factors associated with use of antidepressant medication subsequent to a diagnosis of breast cancer. We also evaluated the effect of participation in a cancer rehabilitation program on use of antidepressants.......We evaluated factors associated with use of antidepressant medication subsequent to a diagnosis of breast cancer. We also evaluated the effect of participation in a cancer rehabilitation program on use of antidepressants....

  14. Rapid quenching effects in PVC films

    Science.gov (United States)

    Lee, H. D.; Mandell, J. F.; Mcgarry, F. J.

    1981-01-01

    Using a specially constructed microbalance for hydrostatic weighing, density changes in PVC thin films (with no additives, 30-100 micrometers thick), due to rapid quenching (approximately 300 C/sec) through the glass transition temperature, have been observed. The more severe the quench, the greater is the free volume content. Isobaric volume recovery of PVC has also been studied by volume dilatometry. Both show aging of relaxing molecular rearrangements takes place as a linear function of logarithmic aging time at room temperature. Distribution of retardation times and Primak's distributed activation energy spectra have been applied to the volume recovery data. The concomitant changes in mechanical properties of PVC after quenching have been monitored by tensile creep and stress-strain to failure. All reflect the presence of excess free volume content, due to rapid quenching.

  15. Nitric Oxide Synthase Inhibitors as Antidepressants

    DEFF Research Database (Denmark)

    Wegener, Gregers; Volke, Vallo

    2010-01-01

    Affective and anxiety disorders are widely distributed disorders with severe social and economic effects. Evidence is emphatic that effective treatment helps to restore function and quality of life. Due to the action of most modern antidepressant drugs, serotonergic mechanisms have traditionally...... as in prophylaxis. This paper reviews the effect of drugs modulating NO synthesis in anxiety and depression....

  16. Impact of antidepressant treatment: a study from The Netherlands

    Directory of Open Access Journals (Sweden)

    van Dongen N

    2012-07-01

    Full Text Available Nadine van Dongen,1 Scott Mason21PIP Health Ltd, London, United Kingdom; 2London Metropolitan University, London, United KingdomBackground: The purpose of the study was to identify the extent and severity of treatment-related side effects experienced by patients with depression. The study was designed to identify the extent of the different antidepressant side effects to gain an understanding of their impact on the lives of patients suffering from depression.Methods: A total of 303 patients from The Netherlands with physician-diagnosed depression completed an online questionnaire. All participating patients were receiving antidepressants and were members of the Patient Intelligence Panel (PIP. Participants answered questions about their antidepressant medication, degree of personal research into antidepressant medication, and about any side effects they had experienced as a result of their current antidepressant therapy, the severity of any such side effects, and the impact on their daily lives.Results: Over two-thirds (69% of patients were receiving antidepressant therapy for the first time. Forty-two percent (42% of patients felt it took 2–6 weeks of antidepressant therapy before their depressive mood improved. More than half of participating patients (60% had experienced side effects from their antidepressant therapy, the most common being ‘somnolence, drowsiness, or fatigue’ (14%. Of the 60% of patients who had experienced side effects, 46% admitted to absenteeism as a consequence.Conclusion: Central to the effective management of depression is an understanding of the effects of antidepressant therapy on patients’ lives. Treatment-related side effects, and their potential influence on treatment discontinuation, need to be recognized and assessed on an individual patient basis to optimize management and minimize potential relapse.Keywords: depression, antidepressants, SSRI, side effects, The Netherlands

  17. Possible Involvement of µ Opioid Receptor in the Antidepressant-Like Effect of Shuyu Formula in Restraint Stress-Induced Depression-Like Rats

    Directory of Open Access Journals (Sweden)

    Fu-rong Wang

    2015-01-01

    Full Text Available Recently μ opioid receptor (MOR has been shown to be closely associated with depression. Here we investigated the action of Shuyu, a Chinese herbal prescription, on repeated restraint stress induced depression-like rats, with specific attention to the role of MOR and the related signal cascade. Our results showed that repeated restraint stress caused significant depressive-like behaviors, as evidenced by reduced body weight gain, prolonged duration of immobility in forced swimming test, and decreased number of square-crossings and rearings in open field test. The stress-induced depression-like behaviors were relieved by Shuyu, which was accompanied by decreased expression of MOR in hippocampus. Furthermore, Shuyu upregulated BDNF protein expression, restored the activity of CREB, and stimulated MEK and ERK phosphorylation in hippocampus of stressed rats. More importantly, MOR is involved in the effects of Shuyu on these depression-related signals, as they can be strengthened by MOR antagonist CTAP. Collectively, these data indicated that the antidepressant-like properties of Shuyu are associated with MOR and the corresponding CREB, BDNF, MEK, and ERK signal pathway. Our study supports clinical use of Shuyu as an effective treatment of depression and also suggests that MOR might be a target for treatment of depression and developing novel antidepressants.

  18. [Modification of sexual functions by antidepressants].

    Science.gov (United States)

    Baier, D; Philipp, M

    1994-01-01

    Sexual dysfunctions appear to be frequently occurring adverse events in treatment with antidepressants. Due to methodological reasons, a reliable estimation of the frequency of such events is currently not yet possible. There is evidence, that antidepressants could be differentiated with respect to their potency and specificity for disturbances of certain sexual subfunctions according to their pharmacological profile. With SSRIs in particular impaired functions of orgasm and ejaculation can be observed. No deteriorations are reported for buproprion and an improvement of sexual dysfunctions within the course of treatment for moclobemide. Viloxazine and trazodone appear to possess marked stimulating effects on libido and erectile functions. Generally the incidence of sexual adverse events is underestimated, although there is a pronounced impact on patient compliance. Taking into account this well documented side effect, sexual impairments should be monitored carefully within antidepressive treatment.

  19. Poisoining with Tricyclic Antidepressants and Current Treatment

    Directory of Open Access Journals (Sweden)

    Muge Gulen

    2016-12-01

    Full Text Available Poisoning with tricyclic antidepressants is one of the main causes of morbidity and mortality compared to all the antidepressants. Main toxic effects are on the cardiovascular system and central nervous system and manifests itself as anticholinergic symptoms. There is no antidote known to be used in the treatment. But sodium bicarbonate treatment is effective in preventing ventricular arrhythmias and hypotension, and resolving metabolic acidosis. There are some treatments that has been used for relief of symptoms and some of them still are in research stage. The drugs that are used can be customized according to the patients symptoms. [Archives Medical Review Journal 2016; 25(4.000: 608-621

  20. Screening of the Antidepressant-like Activity of Two Hypericum ...

    African Journals Online (AJOL)

    The widespread use of Hypericum perforatum for the treatment of mild to moderate depression has prompted screening of the antidepressant-like effect of other species of the genus. The present study was designed to assess the antidepressant-like activity of the 80% methanol extract of Hypericum quartinianum and ...

  1. Efficacy of antidepressants on orofacial pain: a systematic review

    NARCIS (Netherlands)

    Martin, W.J.J.M.; Perez, R.S.G.M.; Tuinzing, D.B.; Forouzanfar, T.

    2012-01-01

    Orofacial pain is a common complaint with multiple diagnoses. There is controversy about the effectiveness of antidepressants for the management of orofacial pain disorders. In order to be able to make a best evidence choice between available antidepressants for the treatment of orofacial pain, a

  2. Antidepressant-like effects of ginsenosides: A comparison of ginsenoside Rb3 and its four deglycosylated derivatives, Rg3, Rh2, compound K, and 20(S)-protopanaxadiol in mice models of despair.

    Science.gov (United States)

    Zhang, Hualin; Li, Zhong; Zhou, Zhongliu; Yang, Hongyan; Zhong, Zhiyong; Lou, Caixia

    2016-01-01

    Ginsenoside Rb3 has been proved to have antidepressant-like effects, which possesses 1 xylose and 3 glucose moieties with 20(S)-protopanaxadiol (PPD) as the aglycone. However, it is commonly accepted that orally ingested ginsenosides can be deglycosylated or partially deglycosylated into active derivatives by the intestinal bacteria. To identify potential antidepressant drug candidates, we compared the antidepressant-like activities between ginsenoside Rb3 and its four deglycosylated derivatives, Rg3, Rh2, compound K (C-K), and PPD. Effects of acute (1-day), short chronic (7-days), and longer chronic treatments (14-days) with these ginsenosides (50 and 100mg/kg, p.o.) on the behavioral changes in the forced swim test (FST), tail suspension test (TST) and open field test were investigated. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels and mouse brain monoamine neurotransmitters 5-HT, NA and DA levels were measured using commercially available competitive enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, C-K showed antidepressant-like activities similar to that of Rb3, and Rg3 displayed antidepressant-like effects at lower dosage and faster time, indicating it has better effects than Rb3, whereas Rh2 and PPD failed to show any effect. Our results also showed, unlike the positive control fluoxetine, Rb3, Rg3 and C-K significantly increased the NA levels in the brain regions of mice exposed to FST but did not affect the 5-HT and DA levels. Moreover, treatment with Rg3 could reverse swim stress-induced increased levels of serum ACTH and corticosterone. These results suggest that C-K and Rg3 are the active deglycosylated derivatives, especially the latter compound, which is more potent than Rb3 and exerts antidepressant-like effects by regulating NA, ACTH and corticosterone levels. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. The α2C-adrenoceptor antagonist, ORM-10921, exerts antidepressant-like effects in the Flinders Sensitive Line rat.

    Science.gov (United States)

    Uys, Madeleine M; Shahid, Mohammed; Sallinen, Jukka; Harvey, Brian H

    2017-02-01

    Depression involves deficits in monoaminergic neurotransmission. Differential roles for α2A, B and C subtypes of the α2-adrenoceptor (AR) are evident, with selective α2C-AR antagonists purported to have antidepressant and procognitive properties. However, this has not been demonstrated in a genetic animal model of depression. The role of the α2C-AR in modulating two key depression-related behaviours in the Flinders Sensitive Line (FSL) rat was studied using a dose-response analysis following subcutaneous administration with the selective α2C-AR antagonist ORM-10921 (0.03; 0.3 mg/kg), the nonselective α2-AR antagonist idazoxan (3 mg/kg), or vehicle once daily for 14 days. Behaviour in the novel object recognition test, forced swim test (FST) and locomotor activity test was assessed. To ratify the validity of the FSL model, the reference tricyclic antidepressant imipramine (15 mg/kg, intraperitoneally) was used as a comparator drug in the FST. FSL rats demonstrated significantly increased immobility and recognition memory deficits versus Flinders Resistant Line controls, with imipramine significantly reversing said immobility. Similarly, ORM-10921 at both doses but not idazoxan significantly reversed immobility in the FST as well as attenuated cognitive deficits in FSL animals. We conclude that selective α2C-AR antagonism has potential as a novel therapeutic strategy in the treatment of depression and cognitive dysfunction.

  4. Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice.

    Science.gov (United States)

    Zheng, Xiao; Ma, Sijing; Kang, An; Wu, Mengqiu; Wang, Lin; Wang, Qiong; Wang, Guangji; Hao, Haiping

    2016-01-19

    The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals.

  5. The bio-distribution of the antidepressant clomipramine is modulated by chronic stress in mice: Effects on behavior

    Directory of Open Access Journals (Sweden)

    Georgia eBalsevich

    2015-01-01

    Full Text Available Major depression is one of the most common psychiatric disorders, severely affecting the quality of life of millions of people worldwide. Despite the availability of several classes of antidepressants, treatment efficacy is still very variable and many patients do not respond to the treatment. Clomipramine (CMI, a classical and widely used antidepressant, shows widespread interindividual variability of efficacy, while the environmental factors contributing to such variability remain unclear. We investigated whether chronic stress modulates the bio-distribution of CMI, and as a result the behavioral response to CMI treatment in a mouse model of chronic social defeat stress. Our results show that stress exposure increased anxiety-like and depressive-like behaviors and altered the stress response. Chronic defeat stress furthermore significantly altered CMI bio-distribution. Interestingly, CMI bio-distribution highly correlated with anxiety-like and depressive-like behaviors only under basal conditions. Taken together, we provide first evidence demonstrating that chronic stress exposure modulates CMI bio-distribution and behavioral responses. This may contribute to CMI’s broad interindividual variability, and is especially relevant in clinical practice.

  6. Suicidality: risk factors and the effects of antidepressants. The example of parallel reduction of suicidality and other depressive symptoms during treatment with the SNRI, milnacipran

    Directory of Open Access Journals (Sweden)

    Philippe Courtet

    2010-08-01

    Full Text Available Philippe CourtetCHRU Montpellier, Inserm U888, University of Montpellier I, Montpellier, FranceAbstract: Suicidal behavior (SB represents a major public health issue. Clinical and basic research suggests that SB is a specific entity in psychiatric nosology involving a combination of personality traits, genetic factors, childhood abuse and neuroanatomical abnormalities. The principal risk factor for suicide is depression. More than 60% of patients who complete suicide are depressed at the time of suicide, most of them untreated. There has been a controversy concerning a possible increased risk of SB in some depressed patients treated with antidepressants. Most recent evidence suggests, however, that treatment of depressed patients is associated with a favorable benefit-risk ratio. A recent study has determined the effects of 6 weeks of antidepressant treatment with the serotonin and norepinephrine reuptake inhibitor, milnacipran, on suicidality in a cohort of 30 patients with mild to moderate depression. At baseline, mild suicidal thoughts were present in 46.7% of patients. Suicidal thoughts decreased progressively throughout the study in parallel with other depressive symptoms and were essentially absent at the end of the study. At no time during treatment was there any indication of an increased suicidal risk. Retardation and psychic anxiety decreased in parallel possibly explaining the lack of any “activation syndrome” in this study.Keywords: suicide, milnacipran, SNRI, activation syndrome

  7. Antidepressants versus interpersonal psychotherapy in treating ...

    African Journals Online (AJOL)

    Both pharmacotherapy and psychotherapy may be equally effective in the treatment of depression in HIV-positive patients. The choice of treatment will be influenced by factors such as adverse effects of antidepressants and adding another medication to an already complex antiretroviral regimen. In such cases, IPT may be ...

  8. Potential Antidepressant Constituents of Nigella sativa Seeds.

    Science.gov (United States)

    Elkhayat, Ehab S; Alorainy, Mohammad S; El-Ashmawy, Ibrahim M; Fat'hi, Shawkat

    2016-01-01

    Nigella sativa Linn. is well known seed in the Middle East, Asia, and the Far East as a natural remedy for many ailments and as a flavoring agent proclaimed medicinal usage dating back to the ancient Egyptians, Greeks, and Romans. An authentic saying of the Prophet Muhammad (Peace Be Upon Him) about black seed is also quoted in Al-Bukhari. This study was carried out to evaluate the antidepressant effect and isolate the potential antidepressant constituents of the polar extract of N. sativa seeds. The antidepressant effect was evaluated through the immobility duration in tail suspension and forced swim tests (FSTs). Albino mice were orally treated with N. sativa polar extract and its RP-18 column chromatography fractions (50 and 100 mg/kg,). The polar extract and two of its sub-fractions were significantly able to decrease the immobility time of mice when subjected to both tail suspension and FSTs, the effects are comparable to standard drug (Sertraline, 5 mg/kg). However, these treatments did not affect the number of crossings and rearing in the open field test. Phytochemical investigation of the two active fractions led to the isolation of quercetin-3-O-α-L-rhamnopyranoside 1, quercetin-7-O-β-D-gluco- pyranoside 2, tauroside E 3, and sapindoside B as the potential antidepressant constituents. Phytochemical and biological evaluation the antidepressant constituents in Nigella sativa using the tail suspension and forced swim methods afforded the isolation and identification of quercetin-3-O-α-L rhamnopyranoside, quercetin-7-O-β-D gluco pyranoside, tauroside E, and sapindoside B as the potential antidepressant constituents in the polar extract of N. sativa. The isolated compounds were identified through extensive NMR analysis (1D, 2D, ESI MS). Abbreviations used: TST: Tail suspension test, FST: Forced swim test, OFT: An Open field test.

  9. Prevalence and patterns of antidepressant drug use during pregnancy.

    Science.gov (United States)

    Ververs, Tessa; Kaasenbrood, Hans; Visser, Gerard; Schobben, Fred; de Jong-van den Berg, Lolkje; Egberts, Toine

    2006-10-01

    The aim of this study was to determine the extent and patterns of antidepressant use before, during and after pregnancy in a large population in The Netherlands. Health care records and prescription data from one of the largest Dutch health insurance companies were analysed. The study cohort consisted of 29,005 women who had live births in the period between January 2000 and July 2003. Antidepressant drug use during a specified period was defined as there being a record of a prescription during that period. During the first trimester of pregnancy 2% of all pregnant women of the study cohort were found to have taken antidepressants; in the second and third trimesters, this figure had dropped to 1.8% of all pregnancies. Antidepressant use before as well as during pregnancy was almost twofold higher in women over 35 years of age than in those under 35 years. Almost 60% of the women who used antidepressants before pregnancy stopped taking them in the first trimester, and a smaller number stopped thereafter. Of all women using antidepressants during pregnancy, one third started this medication during gestation. In the 3 months following delivery, the prevalence of antidepressant use was the same as before pregnancy (2.9%). There was no shift to benzodiazepines in the group of women who stopped taking antidepressants during pregnancy. Although paroxetine and fluoxetine were the most frequently used antidepressants among the study group, all modern antidepressants were used. A considerable number of women are being exposed to antidepressants throughout pregnancy up until delivery. One consequence of this is that their newborns need special care and supervision during the first days of life. However, women who stop taking the medication may risk a relapse of their illness, and this may also have a negative effect on the child.

  10. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design.

    Directory of Open Access Journals (Sweden)

    Jean Mazella

    2010-04-01

    Full Text Available Current antidepressant treatments are inadequate for many individuals, and when they are effective, they require several weeks of administration before a therapeutic effect can be observed. Improving the treatment of depression is challenging. Recently, the two-pore domain potassium channel TREK-1 has been identified as a new target in depression, and its antagonists might become effective antidepressants. In mice, deletion of the TREK-1 gene results in a depression-resistant phenotype that mimics antidepressant treatments. Here, we validate in mice the antidepressant effects of spadin, a secreted peptide derived from the propeptide generated by the maturation of the neurotensin receptor 3 (NTSR3/Sortilin and acting through TREK-1 inhibition. NTSR3/Sortilin interacted with the TREK-1 channel, as shown by immunoprecipitation of TREK-1 and NTSR3/Sortilin from COS-7 cells and cortical neurons co-expressing both proteins. TREK-1 and NTSR3/Sortilin were colocalized in mouse cortical neurons. Spadin bound specifically to TREK-1 with an affinity of 10 nM. Electrophysiological studies showed that spadin efficiently blocked the TREK-1 activity in COS-7 cells, cultured hippocampal pyramidal neurons, and CA3 hippocampal neurons in brain slices. Spadin also induced in vivo an increase of the 5-HT neuron firing rate in the Dorsal Raphe Nucleus. In five behavioral tests predicting an antidepressant response, spadin-treated mice showed a resistance to depression as found in TREK-1 deficient mice. More importantly, an intravenous 4-d treatment with spadin not only induced a strong antidepressant effect but also enhanced hippocampal phosphorylation of CREB protein and neurogenesis, considered to be key markers of antidepressant action after chronic treatment with selective serotonin reuptake inhibitors. This work also shows the development of a reliable method for dosing the propeptide in serum of mice by using AlphaScreen technology. These findings point out

  11. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design.

    Science.gov (United States)

    Mazella, Jean; Pétrault, Olivier; Lucas, Guillaume; Deval, Emmanuel; Béraud-Dufour, Sophie; Gandin, Carine; El-Yacoubi, Malika; Widmann, Catherine; Guyon, Alice; Chevet, Eric; Taouji, Said; Conductier, Grégory; Corinus, Alain; Coppola, Thierry; Gobbi, Gabriella; Nahon, Jean-Louis; Heurteaux, Catherine; Borsotto, Marc

    2010-04-13

    Current antidepressant treatments are inadequate for many individuals, and when they are effective, they require several weeks of administration before a therapeutic effect can be observed. Improving the treatment of depression is challenging. Recently, the two-pore domain potassium channel TREK-1 has been identified as a new target in depression, and its antagonists might become effective antidepressants. In mice, deletion of the TREK-1 gene results in a depression-resistant phenotype that mimics antidepressant treatments. Here, we validate in mice the antidepressant effects of spadin, a secreted peptide derived from the propeptide generated by the maturation of the neurotensin receptor 3 (NTSR3/Sortilin) and acting through TREK-1 inhibition. NTSR3/Sortilin interacted with the TREK-1 channel, as shown by immunoprecipitation of TREK-1 and NTSR3/Sortilin from COS-7 cells and cortical neurons co-expressing both proteins. TREK-1 and NTSR3/Sortilin were colocalized in mouse cortical neurons. Spadin bound specifically to TREK-1 with an affinity of 10 nM. Electrophysiological studies showed that spadin efficiently blocked the TREK-1 activity in COS-7 cells, cultured hippocampal pyramidal neurons, and CA3 hippocampal neurons in brain slices. Spadin also induced in vivo an increase of the 5-HT neuron firing rate in the Dorsal Raphe Nucleus. In five behavioral tests predicting an antidepressant response, spadin-treated mice showed a resistance to depression as found in TREK-1 deficient mice. More importantly, an intravenous 4-d treatment with spadin not only induced a strong antidepressant effect but also enhanced hippocampal phosphorylation of CREB protein and neurogenesis, considered to be key markers of antidepressant action after chronic treatment with selective serotonin reuptake inhibitors. This work also shows the development of a reliable method for dosing the propeptide in serum of mice by using AlphaScreen technology. These findings point out spadin as a putative

  12. Antidepressant-like effect of bright light is potentiated by L-serine administration in a mouse model of seasonal affective disorder.

    Science.gov (United States)

    Kawai, Misato; Goda, Ryosei; Otsuka, Tsuyoshi; Iwamoto, Ayaka; Uotsu, Nobuo; Furuse, Mitsuhiro; Yasuo, Shinobu

    2015-09-01

    Bright light therapy is used as the primary treatment for seasonal affective disorder; however, the mechanisms underlying its antidepressant effect are not fully understood. Previously, we found that C57BL/6J mice exhibit increased depression-like behavior during a short-day condition (SD) and have lowered brain serotonin (5-HT) content. This study analyzed the effect of bright light on depression-like behaviors and the brain serotonergic system using the C57BL/6J mice. In the mice maintained under SD, bright light treatment (1000 lx, daily 1 h exposure) for 1 week reduced immobility time in the forced swimming test and increased intake of saccharin solution in a saccharin intake test. However, the light treatment did not modify 5-HT content and selective 5-HT uptake in the amygdala, or temporal patterns of core body temperature and wheel-running activity throughout a day. In the next experiment, we attempted to enhance the effect of bright light by using L-serine, a precursor of D-serine that acts as an N-methyl-D-aspartic acid receptor coagonist. Daily subcutaneous injection of L-serine for 2 weeks prior to the bright light strongly reduced the immobility time in the forced swimming test, suggesting a synergistic effect of light and L-serine. Furthermore, bright light increased the total number of 5-HT-immunoreactive cells and cells that had colocalized 5-HT and c-Fos immunosignals in several subregions of the raphe nuclei. These effects were potentiated by prior injection of L-serine. These data suggest that the bright light may elicit an antidepressant-like effect via enhanced 5-HT signals in the brain and L-serine can enhance these effects. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Nicotine, but not mecamylamine, enhances antidepressant-like effects of citalopram and reboxetine in the mouse forced swim and tail suspension tests

    DEFF Research Database (Denmark)

    Andreasen T., Jesper; Redrobe, John P

    2009-01-01

    activity and facilitates serotonin and noradrenaline release. Thus, we hypothesise that nicotine may enhance the behavioural effects of serotonin (e.g., citalopram) and/or noradrenaline (e.g., reboxetine) reuptake inhibitors. Here, we tested if nicotine enhanced the activity of citalopram or reboxetine...... in the mouse forced swim test (mFST) and the mouse tail suspension test (mTST). The potential for mecamylamine to augment antidepressant drug action was also investigated. Sub-threshold and threshold doses of citalopram (3 and 10mg/kg) or reboxetine (3, 10 and 20mg/kg) were tested alone and in combination...... and 10mg/kg citalopram and 3 and 10mg/kg reboxetine in the mTST. No concomitant locomotor stimulation was observed at the tested dose combinations. Mecamylamine was effective on its own in some tests, but did not augment the effects of citalopram or reboxetine at the doses tested. The data show...

  14. Acute reversible inactivation of the bed nucleus of stria terminalis induces antidepressant-like effect in the rat forced swimming test

    Directory of Open Access Journals (Sweden)

    Joca Sâmia RL

    2010-06-01

    Full Text Available Abstract Background The bed nucleus of stria terminalis (BNST is a limbic forebrain structure involved in hypothalamo-pituitary-adrenal axis regulation and stress adaptation. Inappropriate adaptation to stress is thought to compromise the organism's coping mechanisms, which have been implicated in the neurobiology of depression. However, the studies aimed at investigating BNST involvement in depression pathophysiology have yielded contradictory results. Therefore, the objective of the present study was to investigate the effects of temporary acute inactivation of synaptic transmission in the BNST by local microinjection of cobalt chloride (CoCl2 in rats subjected to the forced swimming test (FST. Methods Rats implanted with cannulae aimed at the BNST were submitted to 15 min of forced swimming (pretest. Twenty-four hours later immobility time was registered in a new 5 min forced swimming session (test. Independent groups of rats received bilateral microinjections of CoCl2 (1 mM/100 nL before or immediately after pretest or before the test session. Additional groups received the same treatment and were submitted to the open field test to control for unspecific effects on locomotor behavior. Results CoCl2 injection into the BNST before either the pretest or test sessions reduced immobility in the FST, suggesting an antidepressant-like effect. No significant effect of CoCl2 was observed when it was injected into the BNST immediately after pretest. In addition, no effect of BNST inactivation was observed in the open field test. Conclusion These results suggest that acute reversible inactivation of synaptic transmission in the BNST facilitates adaptation to stress and induces antidepressant-like effects.

  15. The effect of flexible cognitive-behavioural therapy and medical treatment, including antidepressants on post-traumatic stress disorder and depression in traumatised refugees: pragmatic randomised controlled clinical trial.

    Science.gov (United States)

    Buhmann, Caecilie Böck; Nordentoft, Merete; Ekstroem, Morten; Carlsson, Jessica; Mortensen, Erik Lykke

    2016-03-01

    Little evidence exists on the treatment of traumatised refugees. To estimate treatment effects of flexible cognitive-behavioural therapy (CBT) and antidepressants (sertraline and mianserin) in traumatised refugees. Randomised controlled clinical trial with 2 × 2 factorial design (registered with Clinicaltrials.gov, NCT00917397, EUDRACT no. 2008-006714-15). Participants were refugees with war-related traumatic experiences, post-traumatic stress disorder (PTSD) and without psychotic disorder. Treatment was weekly sessions with a physician and/or psychologist over 6 months. A total of 217 of 280 patients completed treatment (78%). There was no effect on PTSD symptoms, no effect of psychotherapy and no interaction between psychotherapy and medicine. A small but significant effect of treatment with antidepressants was found on depression. In a pragmatic clinical setting, there was no effect of flexible CBT and antidepressants on PTSD, and there was a small-to-moderate effect of antidepressants and psychoeducation on depression in traumatised refugees. © The Royal College of Psychiatrists 2016.

  16. Banana fruit pulp and peel involved in antianxiety and antidepressant effects while invigorate memory performance in male mice: Possible role of potential antioxidants.

    Science.gov (United States)

    Samad, Noreen; Muneer, Aqsa; Ullah, Najeeb; Zaman, Aqal; Ayaz, M Mazhar; Ahmad, Ijaz

    2017-05-01

    The present study was aimed to investigate the anti-stress and memory enhancing effects of banana (Musa sapientum L.) fruit pulp and peel extract in male mice. Locally bred albino Wistar mice were divided into control and 2 test groups (n=10). Control rats received drinking water while test groups were treated with banana fruit pulp (600 mg/kg; oral administration) and extract of banana peel (400mg/kg; oral administration). Behavioral activities of animals were monitored 14 days post administration of banana pulp and peel extract. Depression-like symptoms were measured by forced swimming test (FST). Anxiety like behavior was monitored using light-dark activity (LDA) test and plus maze activity (PMA) test and memory functions of rats were assessed by morris water maze (MWM) test. Following 2 weeks animals were decapitated and brain was removed for estimation of antioxidant enzymes such as catalase (CAT), super oxide dismutase (SOD) and reduced glutathione (GSH). In the present study both banana peel and pulp increased the time spent in light box and open arm, suggesting anxiolytic effects. A significant decrease in immobility time was observed in FST in both banana pulp and peel treated animals suggesting antidepressant like effects. Moreover, learning and memory assessed by MWM showed decrease in time to reach platform in both short term and long term memory test suggested increased memory function in both banana pulp and peel treated animals as compared to control animals. The activities of all antioxidant enzymes were significantly (ppeel treated animals than control. It is concluded that both banana pulp and peel have anti-anxiety, antidepressant effect as well as strengthen the memory possibly via its antioxidant mechanism. Therefore, it is recommended that supplementation of banana could be taken a vital role in stress (anxiety and depression) relief and increased in memory function possibly by phyto-antioxidants.

  17. Antidepressant-like effects of curcumin on serotonergic receptor-coupled AC-cAMP pathway in chronic unpredictable mild stress of rats.

    Science.gov (United States)

    Li, Yu-Cheng; Wang, Fu-Meng; Pan, Ying; Qiang, Li-Qin; Cheng, Guang; Zhang, Wei-Yun; Kong, Ling-Dong

    2009-04-30

    Serotonergic receptors take their physiologic effects by affecting adenylyl cyclase (AC) catalytic activity and cyclic adenosine monophosphate (cAMP) concentration. AC-cAMP second messenger pathway has been recently suggested to play an important role in depression. Therefore, the compound that regulates the signal pathway may have potential as antidepressant. Curcumin is the main component of Curcuma longa L, a well-known indigenous herb with comprehensive bioactivities. In the present study, we investigated the effects of chronic unpredictable mild stress (CUMS) and curcumin on behaviours and serotonergic receptor-coupled AC-cAMP signal pathway in rats. Curcumin produced beneficial effects on the stressed rats by effectively improving CUMS-induced low sucrose consumption and reducing serum corticosterone levels in rats. Moreover, curcumin enhanced AC activity and cAMP levels in platelet and various brain regions, and up-regulated mRNA expressions of AC subtypes AC 2, AC 8 and cAMP response element binding protein (CREB) in the hippocampus, cortex and hypothalamus of the CUMS rats. Curcumin also attenuated CUMS-induced reductions of 5-hydroxytryptamine (5-HT) levels and high expressions of central 5-HT(1A/1B/7) receptors in rats. These results suggested that the potent antidepressant property of curcumin might be attributed to its improvement of AC-cAMP pathway as well as CREB via suppressing central 5-HT(1A/1B/7) receptors in the CUMS rats. Our findings provided a basis for examining the interaction of serotonergic receptors and AC-cAMP pathway in depression and curcumin treatment.

  18. Gastroprotective and antidepressant effects of a new zinc(II)-curcumin complex in rodent models of gastric ulcer and depression induced by stresses.

    Science.gov (United States)

    Mei, Xueting; Xu, Donghui; Xu, Sika; Zheng, Yanping; Xu, Shibo

    2011-07-01

    Curcumin, a yellow pigment found in the rhizome of Curcuma loga, has been used to treat a variety of digestive and neuropsychiatric disorders since ancient times in China. Curcumin can chelate various metal ions to form metallocomplexes of curcumin which show greater effects than curcumin alone. This study investigated the antiulcerogenic and antidepressant effects of a Zn(II)-curcumin complex on cold-restraint stress (CRS)-induced gastric ulcers in rats, and on the forced swimming test (FST), tail suspension test (TST) and 5-hydroxy-l-tryptophan (5-HTP)-induced head twitch test in mice. CRS disrupted the rat mucosal barrier and induced gastric ulcers by decreasing the activities of the antioxidant enzymes, and increasing H(+)-K(+)-ATPase activity and malondialdehyde (MDA) level. Pretreatment with Zn(II)-curcumin (12, 24, and 48mg/kg) dose-dependently reversed these trends, reduced gastric lesions and H(+)-K(+)-ATPase activity, and increased antioxidant activities compared with control groups. Zn(II)-curcumin significantly increased HSP70 mRNA, and attenuated increased iNOS mRNA in the mucosa. Zn(II)-curcumin (17, 34, and 68mg/kg) also significantly decreased immobility time in the FST and TST, and enhanced 5-HTP-induced head twitches in mice. These results demonstrate that the Zn(II)-curcumin complex showed significant gastroprotective and antidepressant effects compared with curcumin alone via a synergistic effect between curcumin and zinc. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  19. Mind your state: Insights into antidepressant nonadherence ...

    African Journals Online (AJOL)

    Major depressive disorder (MDD) is an insidious disease and affects up to 15% of the global population. Although MDD responds to a wide range of pharmacological treatment options, a number of factors, i.e. not adhering to treatment for at least 4–12 months, contribute to antidepressants not being highly effective.

  20. Depression, antidepressants, and sexual function.

    Science.gov (United States)

    Victor, B S

    1995-08-01

    Recent studies have suggested that serotonin reuptake inhibitors (SSRI's), prescribed for the relief of depression, can cause sexual dysfunction in up to fifty percent of those taking them. The SSRI's--including fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)--affect mood stabilization by promoting the transmission of the neurotransmitter serotonin, although enhancing serotonergic function can decrease libido or lead to erectile difficulties. As an alternative to lowering antidepressant dosages and risking losing therapeutic gains, administering serotonin-blockers, such as cyproheptadine (Periactin) and yohimbine (Yocon), has been shown to restore sexual function. However, the serotonin antagonist, cyproheptadine, causes sedation and can reverse the antidepressant or anti-obsessive effect of the SSRI. Yohimbine enhances transmission of the neurotransmitter epinephrine, increasing the flow of blood to erectile tissue and stimulating sexual desire by activating the cerebral cortex. Its drawbacks are increased levels of panic attacks and higher required dosages. Other potential biochemical stratagems are: amantadine (Symmetrel), bromcriptine (Parlodel), and buspirone (Buspar), which enhance dopamine and serotonin transmission; and bethanecol (Urechline), which enhances choline transmission. One study indicates improved sexual response when the nonserotonergic, mildly dopamine-enhancing buproprion (Welbutrin) is substituted for fluoxetine.

  1. Limb-effect of rapidly rotating stars

    Directory of Open Access Journals (Sweden)

    A.B. Morcos

    2013-06-01

    Full Text Available Kerr metric is used to study the limb-effect phenomenon for axially rotating massive stars. The limb-effect phenomenon is concerned by the variation of the red-shift from the center to the limb of star. This phenomenon has been studied before for the sun. The solar gravitational field is assumed to be given by Schwarzschild and Lense-Thirring fields. In this trial, a study of the limb-effect for a massive axially symmetric rotating star is done. The line of site of inclination and the motion of the observer are taken into consideration to interpret a formula for this phenomenon using a general relativistic red-shift formula. A comparison between the obtained formula and previous formulae is given.

  2. Liquid-Phase Microextraction and Gas Chromatographic-Mass Spectrometric Analysis of Antidepressants in Vitreous Humor: Study of Matrix Effect of Human and Bovine Vitreous and Saline Solution.

    Science.gov (United States)

    dos Santos, Marcelo Filonzi; Yamada, Adrian; Seulin, Saskia Carolina; Leyton, Vilma; Pasqualucci, Carlos Augusto Gonçalves; Muñoz, Daniel Romero; Yonamine, Mauricio

    2016-04-01

    In forensic bioanalytical methods, there is a general agreement that calibrators should be prepared by fortifying analytes in matrix-based blank samples (matrix-based). However, in the case of vitreous humor (VH), the collection of blank samples for the validation and for routine analysis would require the availability of many cadavers. Besides the difficulty of obtaining enough blank VH, this procedure could also represent an ethical issue. Here, a study of matrix effect was performed taking into consideration human and bovine vitreous and saline solution (SS) (NaCl 0.9%). Tricyclic antidepressants [amitriptyline (AMI), nortriptyline (NTR), imipramine (IMI) and desipramine (DES)] were used as model analytes and were extracted from samples by means of liquid-phase microextraction and detected by gas chromatography-mass spectrometry. Samples of human and bovine VH and SS were prepared in six different concentrations of antidepressants (5, 40, 80, 120, 160 and 200 ng/mL) and were analyzed. Relative matrix effect was evaluated by applying a two-tailed homoscedastic Student's t-test, comparing the results obtained with the set of data obtained with human VH and bovine VH and SS. No significant matrix effect was found for AMI and NTR in the three evaluated matrices. However, a great variability was observed for IMI and DES for all matrices. Once compatibilities among the matrices were demonstrated, the method was fully validated for AMI and NTR in SS. The method was applied to six VH samples deriving from real cases whose femoral whole blood (FWB) was analyzed by a previously published method. An average ratio (VH/FWB) of ∼ 0.1 was found for both compounds. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Effects of the triple monoamine uptake inhibitor DOV 102,677 on alcohol-motivated responding and antidepressant activity in alcohol-preferring (P) rats.

    Science.gov (United States)

    Yang, Andrew R S T; Yi, Heon S; Warnock, Kaitlin T; Mamczarz, Jacek; June, Harry L; Mallick, Nikhil; Krieter, Philip A; Tonelli, Leonardo; Skolnick, Phil; Basile, Anthony S; June, Harry L

    2012-05-01

      Concurrent inhibitors of dopamine, norepinephrine, and serotonin uptake have been proposed as novel antidepressants. Given the high comorbidity between alcoholism and depression, we evaluated the activity of DOV 102,677 (DOV) on alcohol-maintained responding and performance in the forced swim test (FST), a model of antidepressant (AD) activity, using alcohol-preferring (P) rats.   Following training to lever press for either alcohol (10% v/v) or sucrose (3, 2%, w/v) on a fixed-ratio 4 (FR4) schedule, DOV (1.56 to 50 mg/kg; PO) was given 25 minutes or 24 hours prior to evaluation. The effects of DOV (12.5 to 50 mg/kg; PO) in the FST were evaluated 25 minutes posttreatment.   DOV (6.25 to 50 mg/kg) dose-dependently reduced alcohol-maintained responding by 59 to 88% at 25 minutes posttreatment, without significantly altering sucrose responding. The reduction in alcohol responding (44% at 50 mg/kg) was sustained for up to 120 hours after a single dose. Administration of a single dose of DOV (25, 50 mg/kg) 24 hours before testing suppressed alcohol responding for 48 hours by 59 to 62%. DOV (12.5 to 50 mg/kg) also dose-dependently reduced immobility of P rats in the FST.   DOV produces both prolonged and selective reductions of alcohol-motivated behaviors in P rats. The elimination kinetics of DOV suggests that its long duration of action may be due to an active metabolite. DOV also produced robust AD-like effects in P rats. We propose that DOV may be useful in treating comorbid alcoholism and depression in humans. Copyright © 2011 by the Research Society on Alcoholism.

  4. Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin.

    Science.gov (United States)

    Wang, X; Zhang, D; Lu, X-Y

    2015-04-01

    Compelling evidence supports the important role of the glutamatergic system in the pathophysiology of major depression and also as a target for rapid-acting antidepressants. However, the functional role of glutamate release/transmission in behavioral processes related to depression and antidepressant efficacy remains to be elucidated. In this study, glutamate release and behavioral responses to tail suspension, a procedure commonly used for inducing behavioral despair, were simultaneously monitored in real time. The onset of tail suspension stress evoked a rapid increase in glutamate release in hippocampal field CA3, which declined gradually after its offset. Blockade of N-methyl-D-aspartic acid (NMDA) receptors by intra-CA3 infusion of MK-801, a non-competitive NMDA receptor antagonist, reversed behavioral despair. A subpopulation of granule neurons that innervated the CA3 region expressed leptin receptors and these cells were not activated by stress. Leptin treatment dampened tail suspension-evoked glutamate release in CA3. On the other hand, intra-CA3 infusion of NMDA blocked the antidepressant-like effect of leptin in reversing behavioral despair in both the tail suspension and forced swim tests, which involved activation of Akt signaling in DG. Taken together, these results suggest that the DG-CA3 glutamatergic pathway is critical for mediating behavioral despair and antidepressant-like responses to leptin.

  5. Dentate gyrus–CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin

    Science.gov (United States)

    Wang, Xuezhen; Zhang, Di; Lu, Xin-Yun

    2014-01-01

    Compelling evidence supports the important role of the glutamatergic system in the pathophysiology of major depression and also as a target for rapid-acting antidepressants. However, the functional role of glutamate release/transmission in behavioral processes related to depression and antidepressant efficacy remains to be elucidated. In this study, glutamate release and behavioral responses to tail suspension, a procedure commonly used for inducing behavioral despair, were simultaneously monitored in real time. The onset of tail suspension stress evoked a rapid increase in glutamate release in hippocampal field CA3, which declined gradually after its offset. Blockade of NMDA receptors by intra-CA3 infusion of MK-801, a non-competitive NMDA receptor antagonist, reversed behavioral despair. The CA3 was innervated by granule neurons expressing the leptin receptor (LepRb) in the dentate gyrus (DG), representing a subpopulation of granule neurons that were devoid of stress-induced activation. Leptin treatment dampened tail suspension-evoked glutamate release in CA3. On the other hand, intra-CA3 infusion of NMDA blocked the antidepressant-like effect of leptin in reversing behavioral despair in both the tail suspension and forced swim tests, which involved activation of Akt signaling in DG. Together, these results suggest that the DG-CA3 glutamatergic pathway is critical for mediating behavioral despair and antidepressant-like responses to leptin. PMID:25092243

  6. Impact of drug tolerability on the selection of antidepressant treatment in patients with major depressive disorder.

    Science.gov (United States)

    Ginsberg, Lawrence D

    2009-12-01

    Despite significant progress in the development of antidepressant therapies, tolerability remains an important factor associated with the selection of appropriate antidepressant treatment. Side effects commonly reported by depressed patients taking antidepressants include weight gain, sexual dysfunction, and gastrointestinal effects.Tolerability issues associated with antidepressants can negatively impact treatment outcomes for patients with major depressive disorder. In addition, a drug's tolerability profile substantially influences a physician's choice of specific antidepressant therapy, Despite the availability of many antidepressants, empirical clinical evidence to guide physicians in making the best choice is limited and not always clear.Thus, it is key for clinicians to understand the short- and long-term outcomes and side effect profiles of the available antidepressants.

  7. Antidepressants in social anxiety disorder

    Directory of Open Access Journals (Sweden)

    Nardi Antonio E.

    2001-01-01

    Full Text Available Social anxiety disorder (SAD is a marked and persistent fear of doing almost everything in front of people due to concerns about being judge by others. An up-to-date review is needed in order to reach a practical judgement of all psychopharmacological data. Case reports, open and double-blind trials with SAD were described and commented upon from a clinical point of view. The MEDLINE system was searched from 1975 to 2001. The references from the selected papers were also used as a source. MAOIs (fenelzine, tranylcypromine, reversible monoamino oxidase-A inhibitors (moclobemide, brofaromine, SSRIs (paroxetine, sertraline, fluoxetine, fluvoxamine and some other antidepressants (venlafaxine, nefazodone have proven effective in several studies with various methodologies. The MAOIs have more serious adverse effects and the SSRIs have the best tolerance. SSRIs are efficacious and the first choice of treatment.

  8. A selective inhibitor of protein kinase A induces behavioural and neurological antidepressant-like effects in rats

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Müller, Heidi Kaastrup; Elfving, Betina

    2011-01-01

    Background: It is well established that cyclic adenosine monophosphate (AMP) signalling via cAMP-dependent protein kinase (PKA) within neurons plays an important role in depression and antidepressant treatment. However, the importance of several newly discovered targets that function independently...... from PKA, such as exchange protein activated by cAMP (Epac), remains unexplored in this regard. Objectives: In this study we used a cAMP analogue that inhibits PKA but not Epac (Rp-8-Br-cAMPS), to explore the modifying actions of these two targets on immobility in the forced swim test (FST...... to the right lateral ventricle and were allowed 7 days for recovery. Animals were subjected to a 15 minute pre-swim followed by a 5 min test swim 24 hours later. Three 5 μl infusions of vehicle (Ringer’s solution) or drug solution (Rp-8-Br-cAMPS (100 nmol), Rp-8-Br-PET-cGMPS (1 nmol) or both) were administered...

  9. Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep Disturbances, and Antidepressant Treatments

    Directory of Open Access Journals (Sweden)

    Meng-Qi Zhang

    2017-01-01

    Full Text Available Depression, which is characterized by a pervasive and persistent low mood and anhedonia, greatly impacts patients, their families, and society. The associated and recurring sleep disturbances further reduce patient’s quality of life. However, therapeutic sleep deprivation has been regarded as a rapid and robust antidepressant treatment for several decades, which suggests a complicated role of sleep in development of depression. Changes in neural plasticity are observed during physiological sleep, therapeutic sleep deprivation, and depression. This correlation might help us to understand better the mechanism underlying development of depression and the role of sleep. In this review, we first introduce the structure of sleep and the facilitated neural plasticity caused by physiological sleep. Then, we introduce sleep disturbances and changes in plasticity in patients with depression. Finally, the effects and mechanisms of antidepressants and therapeutic sleep deprivation on neural plasticity are discussed.

  10. Neural Plasticity Is Involved in Physiological Sleep, Depressive Sleep Disturbances, and Antidepressant Treatments.

    Science.gov (United States)

    Zhang, Meng-Qi; Li, Rui; Wang, Yi-Qun; Huang, Zhi-Li

    2017-01-01

    Depression, which is characterized by a pervasive and persistent low mood and anhedonia, greatly impacts patients, their families, and society. The associated and recurring sleep disturbances further reduce patient's quality of life. However, therapeutic sleep deprivation has been regarded as a rapid and robust antidepressant treatment for several decades, which suggests a complicated role of sleep in development of depression. Changes in neural plasticity are observed during physiological sleep, therapeutic sleep deprivation, and depression. This correlation might help us to understand better the mechanism underlying development of depression and the role of sleep. In this review, we first introduce the structure of sleep and the facilitated neural plasticity caused by physiological sleep. Then, we introduce sleep disturbances and changes in plasticity in patients with depression. Finally, the effects and mechanisms of antidepressants and therapeutic sleep deprivation on neural plasticity are discussed.

  11. Antidepressants in Inflammatory Bowel Disease: A Systematic Review.

    Science.gov (United States)

    Macer, Benjamin J D; Prady, Stephanie L; Mikocka-Walus, Antonina

    2017-04-01

    Antidepressants are commonly used to treat symptoms of anxiety and depression in inflammatory bowel disease (IBD). Recent studies suggest a link between IBD activity and an individual's emotional state which raises the possibility that antidepressants may potentially modify the disease course of IBD. This systematic review thus primarily aims to evaluate the efficacy of antidepressants on IBD activity, and secondarily, on anxiety and depression. MEDLINE, EMBASE, Cochrane (IBD Group), CINAHL, AMED, PsycINFO, and OpenGrey were searched from 1990 onward with no restrictions on study design. A quality appraisal was conducted using several scales as appropriate for each study design. A narrative synthesis was also conducted. Fifteen eligible studies included in the review (1 randomized controlled trial, 2 cohorts, 1 case-control, 1 cross-sectional survey, 1 qualitative, 2 audits, 1 case series, and 6 case reports) examined a range of antidepressants. Twelve studies suggested that antidepressants have a positive impact on IBD course. Nine studies reported anxiety and depression as an outcome, of these 8 reported beneficial effects of antidepressants. Most of the studies were deemed to be at low risk of bias, apart from the case reports, which were at high risk of bias. This research indicates that antidepressants may have a beneficial effect on IBD course. However, it is currently not possible to determine their efficacy for certain because of the lack of randomized trials. Further trials using objective measures of IBD activity, longer follow-up periods, and larger sample sizes are needed.

  12. Treatment Course With Antidepressant Therapy in Late-Life Depression

    National Research Council Canada - National Science Library

    Sheline, Yvette I; Disabato, Brianne M; Hranilovich, Jennifer; Morris, Carrie; D’Angelo, Gina; Pieper, Carl; Toffanin, Tommaso; Taylor, Warren D; MacFall, James R; Wilkins, Consuelo; Barch, Deanna M; Welsh-Bohmer, Kathleen A; Steffens, David C; Krishnan, Ranga R; Doraiswamy, P. Murali

    2012-01-01

    ObjectiveIn order to assess the effect of gray matter volumes and cortical thickness on antidepressant treatment response in late-life depression, the authors examined the relationship between brain...

  13. Antidepressant-Resistant Depression and Antidepressant-Associated Suicidal Behaviour: The Role of Underlying Bipolarity

    OpenAIRE

    Rihmer, Zoltan; Gonda, Xenia

    2011-01-01

    The complex relationship between the use of antidepressants and suicidal behaviour is one of the hottest topics of our contemporary psychiatry. Based on the literature, this paper summarizes the author's view on antidepressant-resistant depression and antidepressant-associated suicidal behaviour. Antidepressant-resistance, antidepressant-induced worsening of depression, antidepressant-associated (hypo)manic switches, mixed depressive episode, and antidepressant-associated suicidality among d...

  14. Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT1A and 5-HT7 Antagonists in Animal Models: e0142499

    National Research Council Canada - National Science Library

    Karolina Pytka; Anna Partyka; Magdalena Jastrzebska-Wiesek; Agata Siwek; Monika Gluch-Lutwin; Barbara Mordyl; Grzegorz Kazek; Anna Rapacz; Adrian Olczyk; Adam Galuszka; Marian Blachuta; Anna Waszkielewicz; Henryk Marona; Jacek Sapa; Barbara Filipek

    2015-01-01

    .... Antidepressant-like properties were investigated in the forced swim test (FST) in mice and rats. Anxiolytic-like activity was evaluated in the four-plate test in mice and elevated plus maze test...

  15. Rapid, cost-effective liquid chromatograghic method for the ...

    African Journals Online (AJOL)

    GRACE

    2006-07-03

    Jul 3, 2006 ... 1Department of Medicinal Chemistry and Quality Control, National Institute for Pharmaceutical Research and Development, Abuja,. Nigeria. ... A rapid and cost effective method for the analysis of metronidazole in biological samples was ... effective HPLC method of assaying metronidazole both in.

  16. Refining cost-effectiveness analyses using the net benefit approach and econometric methods: an example from a trial of anti-depressant treatment.

    Science.gov (United States)

    Sabes-Figuera, Ramon; McCrone, Paul; Kendricks, Antony

    2013-04-01

    Economic evaluation analyses can be enhanced by employing regression methods, allowing for the identification of important sub-groups and to adjust for imperfect randomisation in clinical trials or to analyse non-randomised data. To explore the benefits of combining regression techniques and the standard Bayesian approach to refine cost-effectiveness analyses using data from randomised clinical trials. Data from a randomised trial of anti-depressant treatment were analysed and a regression model was used to explore the factors that have an impact on the net benefit (NB) statistic with the aim of using these findings to adjust the cost-effectiveness acceptability curves. Exploratory sub-samples' analyses were carried out to explore possible differences in cost-effectiveness. Results The analysis found that having suffered a previous similar depression is strongly correlated with a lower NB, independent of the outcome measure or follow-up point. In patients with previous similar depression, adding an selective serotonin reuptake inhibitors (SSRI) to supportive care for mild-to-moderate depression is probably cost-effective at the level used by the English National Institute for Health and Clinical Excellence to make recommendations. This analysis highlights the need for incorporation of econometric methods into cost-effectiveness analyses using the NB approach.

  17. Differentiated effects of the multimodal antidepressant vortioxetine on sleep architecture: Part 2, pharmacological interactions in rodents suggest a role of serotonin-3 receptor antagonism

    OpenAIRE

    Leiser, Steven C; Iglesias-Bregna, Deborah; Westrich, Ligia; Pehrson, Alan L; Sanchez, Connie

    2015-01-01

    Antidepressants often disrupt sleep. Vortioxetine, a multimodal antidepressant acting through serotonin (5-HT) transporter (SERT) inhibition, 5-HT3, 5-HT7 and 5-HT1D receptor antagonism, 5-HT1B receptor partial agonism, and 5-HT1A receptor agonism, had fewer incidences of sleep-related adverse events reported in depressed patients. In the accompanying paper a polysomnographic electroencephalography (sleep-EEG) study of vortioxetine and paroxetine in healthy subjects indicated that at low/inte...

  18. The Clinical and Cost Effectiveness of Vortioxetine for the Treatment of a Major Depressive Episode in Patients With Failed Prior Antidepressant Therapy: A Critique of the Evidence.

    Science.gov (United States)

    Lomas, James; Llewellyn, Alexis; Soares, Marta; Simmonds, Mark; Wright, Kath; Eastwood, Alison; Palmer, Stephen

    2016-09-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of vortioxetine (Lundbeck) to submit clinical and cost-effectiveness evidence for vortioxetine for the treatment of major depressive episodes (MDEs), as part of the Institute's Single Technology Appraisal (STA) process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA367 issued in November 2015. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. Two phase III randomised controlled trials for a second-line population involving vortioxetine were identified-REVIVE and TAK318. These two trials represent only 972 of over 7000 patients included in trials of vortioxetine. In REVIVE, there was a statistically significant difference in depression scores favouring vortioxetine compared with agomelatine [mean Montgomery-Åsberg Depression Rating Scale (MADRS) score difference of 2.16 points; 95 % confidence interval 0.81-3.51]. The ERG concluded that, based on all the evidence, rather than the substantially restricted subset of evidence originally considered by the manufacturer, vortioxetine is likely to be similar in efficacy to other analysed antidepressants [citalopram, sertraline, escitalopram and venlafaxine extended release (XR)], and may be more efficacious than agomelatine and inferior to duloxetine. The ERG concluded that vortioxetine may be more tolerable than other analysed antidepressants (sertraline, venlafaxine XR and bupropion), although the limited data prevent firm conclusions. The base-case incremental cost-effectiveness ratio (ICER) of vortioxetine reported by the manufacturer was £378 per quality

  19. 5-HT2C receptors in the basolateral amygdala and dorsal striatum are a novel target for the anxiolytic and antidepressant effects of exercise.

    Directory of Open Access Journals (Sweden)

    Benjamin N Greenwood

    Full Text Available Physical activity reduces the incidence and severity of psychiatric disorders such as anxiety and depression. Similarly, voluntary wheel running produces anxiolytic- and antidepressant-like effects in rodent models. The specific neurobiological mechanisms underlying the beneficial properties of exercise, however, remain unclear. One relevant pharmacological target in the treatment of psychiatric disorders is the 5-HT(2C receptor (5-HT(2CR. Consistent with data demonstrating the anxiogenic consequences of 5-HT(2CR activation in humans and rodents, we have previously reported that site-specific administration of the selective 5-HT(2CR agonist CP-809101 in the lateral/basolateral amygdala (BLA increases shock-elicited fear while administration of CP-809101 in the dorsal striatum (DS interferes with shuttle box escape learning. These findings suggest that activation of 5-HT(2CR in discrete brain regions contributes to specific anxiety- and depression-like behaviors and may indicate potential brain sites involved in the anxiolytic and antidepressant effects of exercise. The current studies tested the hypothesis that voluntary wheel running reduces the behavioral consequences of 5-HT(2CR activation in the BLA and DS, specifically enhanced shock-elicited fear and interference with shuttle box escape learning. After 6 weeks of voluntary wheel running or sedentary conditions, the selective 5-HT(2CR agonist CP-809101 was microinjected into either the BLA or the DS of adult Fischer 344 rats, and shock-elicited fear and shuttle box escape learning was assessed. Additionally, in-situ hybridization was used to determine if 6 weeks of voluntary exercise changed levels of 5-HT(2CR mRNA. We found that voluntary wheel running reduced the behavioral effects of CP-809101 and reduced levels of 5-HT(2CR mRNA in both the BLA and the DS. The current data indicate that expression of 5-HT(2CR mRNA in discrete brain sites is sensitive to physical activity status of the

  20. Review of a New Multimodal Antidepressant Vortioxetine

    Directory of Open Access Journals (Sweden)

    Oppa M

    2016-08-01

    Full Text Available Vortioxetine is a novel antidepressant with two mechanisms of action – direct effect on several serotonin receptors and serotonin re-uptake inhibition. It shows antidepressant, anxiolytic and cognitive effects during the treatment of major depressive disorder (MDD. The aim of this article was to summarize the use of vortioxetine in clinical studies and assess the efficacy and tolerability. Most of the studies reported a statistically significant efficacy for vortioxetine versus placebo. In addition, vortioxetine showed efficacy in patients with an inadequate response to selective serotonin re-uptake inhibitors (SSRI or serotonin-noradrenaline re-uptake inhibitors (SNRI monotherapy and improved cognitive function in patients with MDD. In these studies, vortioxetine was well tolerated – most common observed adverse effect was nausea – and it was not associated with clinically important changes in laboratory test results or vital signs. Vortioxetine showed a relatively low incidence of sexual dysfunction.

  1. Evaluation of the anxiolytic and antidepressant effects of asiatic acid, a compound from Gotu kola or Centella asiatica, in the male Sprague Dawley rat.

    Science.gov (United States)

    Ceremuga, Tomás Eduardo; Valdivieso, Debra; Kenner, Catherine; Lucia, Amy; Lathrop, Keith; Stailey, Owen; Bailey, Heather; Criss, Jonathan; Linton, Jessica; Fried, Jordan; Taylor, Andrew; Padron, Gina; Johnson, Arthur Don

    2015-04-01

    Herbal medication use continues to rise and interactions with existing medications propose risks and may have significant effects and consequences on the administration of anesthesia. The purpose of this study was to investigate the anxiolytic and antidepressant effects of asiatic acid and its potential modulation of the γ-aminobutyric acid (GABAA) receptor. Fifty-five male Sprague Dawley rats were divided into 5 groups: vehicle (DMSO), asiatic acid (AA), midazolam, or a combination of flumazenil + AA or midazolam + AA, and injected intraperitoneally 30 minutes prior to testing. The rats were tested on the Elevated Plus Maze (EPM) and the Forced Swim Test (FST). Data were analyzed using a two-tailed multivariate analysis of variance (MANOVA). Significance was found regarding the ratio of open arm time, maximum speed, and time spent mobile in the AA group and the midazolam + AA group (P < .05). Flumazenil decreased the anxiolytic effects, suggesting that AA modulates the benzodiazepine site on the GABAA receptor. Further studies are recommended to determine the efficacy of prolonged treatment for anxiety and depression.

  2. The influence of comorbid personality disorder on the effects of behavioural activation vs. antidepressant medication for major depressive disorder: results from a randomized trial in Iran.

    Science.gov (United States)

    Moradveisi, Latif; Huibers, Marcus J H; Renner, Fritz; Arasteh, Modabber; Arntz, Arnoud

    2013-08-01

    There is a disagreement about the impact of personality disorder (PD) on treatment outcome for patients with major depressive disorder (MDD). 100 out-patients with MDD were randomized to 16 sessions of behavioural activation (BA) (n = 50) or antidepressant medication (ADM) (n = 50) in Iran. Main outcome was depression severity, measured with the Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression (HRSD), and assessed at 0, 4, 13 and 49 weeks. Participants with comorbid PDs had higher scores on BDI and HRSD at baseline and throughout the study than participants without comorbid PD. Patients with and without comorbid personality pathology responded equally to treatment on the short-and the long-term. Overall, BA was better in reducing symptoms in patients but this effect was not influenced by comorbid PD. Similar effects were found for a dimensional PD-measure. Only cluster-C PD-traits turned out to be associated with overall depression severity. Cluster-A PD-traits predicted poorer long-term treatment response to ADM and BA, but only on the BDI, not on the HRSD. No effects of cluster-B PD-traits were found. However, PD was associated with higher dropout. The general conclusion is that comorbid PD pathology, especially from cluster-C, is associated with higher depression severity, but not with less response to treatment. Comorbid PD did predict increased chance of dropout. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Antidepressant induced excessive yawning and indifference

    Directory of Open Access Journals (Sweden)

    Bruno Palazzo Nazar

    2015-03-01

    Full Text Available Introduction Antidepressant induced excessive yawning has been described as a possible side effect of pharmacotherapy. A syndrome of indifference has also been described as another possible side effect. The frequency of those phenomena and their physiopathology are unknown. They are both considered benign and reversible after antidepressant discontinuation but severe cases with complications as temporomandibular lesions, have been described. Methods We report two unprecedented cases in which excessive yawning and indifference occurred simultaneously as side effects of antidepressant therapy, discussing possible physiopathological mechanisms for this co-occurrence. Case 1: A male patient presented excessive yawning (approximately 80/day and apathy after venlafaxine XR treatment. Symptoms reduced after a switch to escitalopram, with a reduction to 50 yawns/day. Case 2: A female patient presented excessive yawning (approximately 25/day and inability to react to environmental stressors with desvenlafaxine. Conclusion Induction of indifference and excessive yawning may be modulated by serotonergic and noradrenergic mechanisms. One proposal to unify these side effects would be enhancement of serotonin in midbrain, especially paraventricular and raphe nucleus.

  4. Treatment with tianeptine induces antidepressive-like effects and alters the neurotrophin levels, mitochondrial respiratory chain and cycle Krebs enzymes in the brain of maternally deprived adult rats.

    Science.gov (United States)

    Della, Franciela P; Abelaira, Helena M; Réus, Gislaine Z; Santos, Maria Augusta B dos; Tomaz, Débora B; Antunes, Altamir R; Scaini, Giselli; Morais, Meline O S; Streck, Emilio L; Quevedo, João

    2013-03-01

    Maternally deprived rats were treated with tianeptine (15 mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming and open field tests. The BDNF, NGF and energy metabolism were assessed in the rat brain. Deprived rats increased the immobility time, but tianeptine reversed this effect and increased the swimming time; the BDNF levels were decreased in the amygdala of the deprived rats treated with saline and the BDNF levels were decreased in the nucleus accumbens within all groups; the NGF was found to have decreased in the hippocampus, amygdala and nucleus accumbens of the deprived rats; citrate synthase was increased in the hippocampus of non-deprived rats treated with tianeptine and the creatine kinase was decreased in the hippocampus and amygdala of the deprived rats; the mitochondrial complex I and II-III were inhibited, and tianeptine increased the mitochondrial complex II and IV in the hippocampus of the non-deprived rats; the succinate dehydrogenase was increased in the hippocampus of non-deprived rats treated with tianeptine. So, tianeptine showed antidepressant effects conducted on maternally deprived rats, and this can be attributed to its action on the neurochemical pathways related to depression.

  5. Investigation on the antidepressant effect of sea buckthorn seed oil through the GC-MS-based metabolomics approach coupled with multivariate analysis.