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Sample records for catalepsy

  1. Piracetam reverses haloperidol-induced catalepsy in mice

    OpenAIRE

    SALAM, Omar Abdel; NADA, Somaia

    2011-01-01

    To investigate the memory-enhancing drugs piracetam, vinpocetine, and ginkgo biloba for their ability to reduce catalepsy in mice treated with haloperidol. Haloperidol is a classic neuroleptic drug that induces motor abnormalities and cognitive impairment due to a blockade of dopamine D2 receptors in the striatum. Materials and methods: Catalepsy was induced by intraperitoneal haloperidol (2 mg/kg) administration. The drugs being tested were either administered intraperitoneally (IP) along ...

  2. On the association between lipopolysaccharide induced catalepsy and serotonin metabolism in the brain of mice genetically different in the predisposition to catalepsy.

    Science.gov (United States)

    Bazhenova, Ekaterina Yu; Kulikov, Alexander V; Tikhonova, Maria A; Bazovkina, Daria V; Fursenko, Daria V; Popova, Nina K

    2013-10-01

    The study of the interaction between nervous and immune systems in the mechanism of psychopathology is an important problem of neuroscience. Catalepsy (freezing reaction) is a passive defensive strategy in response to threatening stimuli. An exaggerated form of catalepsy is a syndrome of some grave mental disorders. Both the brain serotonin (5-HT) and immune systems were shown to be involved in the mechanism of catalepsy. Here we compared the effects of two doses (50 or 200 μg/kg, ip) of innate immune system activator, bacterial lipopolysaccharide (LPS), on catalepsy, 5-HT and its main metabolite, 5-hydroxyindole acetic acid (5-HIAA) in the hippocampus, striatum, and midbrain of mice of catalepsy-prone (CBA/Lac and AKR.CBA-D13Mit76) and catalepsy-resistant (AKR/J) strains. The expression of LPS-induced catalepsy as well as 5-HIAA/5-HT ratio in the midbrain and striatum were significantly higher in mice of the catalepsy-prone strains compared with animals of the catalepsy-resistant strains. These results indicated an involvement of the brain 5-HT system in the cataleptogenic effect of LPS and open up new vistas for understanding the nervous-immune mechanism of behavioral disorders. PMID:23994663

  3. Post-trial dopaminergic modulation of conditioned catalepsy: A single apomorphine induced increase/decrease in dopaminergic activation immediately following a conditioned catalepsy response can reverse/enhance a haloperidol conditioned and sensitized catalepsy response.

    Science.gov (United States)

    Oliveira, Lucas Rangel; Dias, Flávia Regina Cruz; Santos, Breno Garone; Silva, Jade Leal Loureiro; Carey, Robert J; Carrera, Marinete Pinheiro

    2016-09-15

    Haloperidol can induce catalepsy and this drug effect can be conditioned as well as sensitized to contextual cues. We used a paired/unpaired Pavlovian conditioning protocol to establish haloperidol catalepsy conditioned and sensitized responses. Groups of rats were given 10 daily catalepsy tests following administration of vehicle (n=24) or haloperidol (1.0mg/kg) either paired (n=18) or unpaired (n=18) to testing. Subsequently, testing for conditioning was conducted and conditioning and sensitization of catalepsy were observed selectively in the paired group. Immediately following a second test for catalepsy conditioning, the groups were subdivided into 4 vehicle groups, 3 unpaired haloperidol groups and 3 paired haloperidol groups and were given one of three post-trial treatments (vehicle, 0.05mg/kg or 2.0mg/kg apomorphine). One day later the conditioned catalepsy test 3 was carried out and on the next day, a haloperidol challenge test was performed. The post-trial apomorphine treatments had major effects on the paired groups upon both conditioning and the haloperidol challenge test. The low dose apomorphine post-trial treatment enhanced both the conditioned and the haloperidol sensitized catalepsy responses. The high dose apomorphine post-trial treatment eliminated conditioned catalepsy and eliminated the initial acute catalepsy response to haloperidol that was induced in the vehicle control groups. These results demonstrate the sensitivity of conditioned drug cues to modification by increases/decreases in activity of the dopamine system in the immediate post-trial interval after a conditioning trial. This demonstration that post-trial dopaminergic drug treatments can modify conditioned drug behavior has broad implications for conditioned drug effects. PMID:27173428

  4. Effect of Different Drugs Influencing Monoamine Neurotransmission on Haloperidol-Induced Catalepsy in Mice

    OpenAIRE

    ABDEL-SALAM, Omar Mohamed

    2007-01-01

    Aim: Catalepsy occurs following high dopamine D2 receptor blockade by the typical antipsychotic drug haloperidol. The present study investigated the effect of different drugs affecting monoamine neurotransmission in this animal model of Parkinson's disease in mice. Materials and Methods: Drugs were intraperitoneally administered with haloperidol 30 min prior to testing. Catalepsy was measured using the bar test. Results: Catalepsy duration was reduced by the non-selective noradrena...

  5. Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats

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    Ionov

    2015-05-01

    Full Text Available Background The decreased level of somatostatin and increased level of histamine are detected in the Parkinsonian brain. In old Wistar rats, the brain somatostatin deficiency can initiate catalepsy that suggests the pathogenic significance of this abnormality in Parkinson’s disease (PD. The ability of histamine to affect the somatostatin deficiency action is not studied. Objectives The current study aimed to examine if histamine alters the cataleptogenic activity of the brain somatostatin deficiency in Wistar rats. Materials and Methods The animals used in the study were 100 - 110 and 736 - 767 days old. Catalepsy was evaluated by the bar test. The inhibition of the brain somatostatin activity was simulated by I.C.V. administration of cyclosomatostatin (cycloSOM, a somatostatin receptor antagonist. Results CycloSOM (0.2, 1.0, and 5.0 µg and histamine (1.0 and 10.0 µg alone were ineffective in both young and old animals. In combination, however, cycloSOM and histamine initiated cataleptic response in old rats. Effect of the combination was inhibited by H1 and H2 but not H3 antagonists. Conclusions CycloSOM and histamine synergistically exert catalepsy in old rats. In light of these data, the combination of the decreased brain level of somatostatin and increased brain level of histamine may be of pathogenic relevance for extrapyramidal signs in PD.

  6. Effect of Tribulus terrestris on haloperidol-induced catalepsy in mice

    OpenAIRE

    B S Nishchal; Rai, S.; Prabhu, M. N.; Sheetal D Ullal; S. Rajeswari; Gopalakrishna, H. N.

    2014-01-01

    Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspend...

  7. Effect of Sodium Valproate pretreatment on Haloperidol induced catalepsy in rats

    OpenAIRE

    Sattigeri Bhagya Manoj; Balsara J J

    2009-01-01

    Sodium valproate a broad spectrum antiepileptic, elevates the brain GABA levels. Studies have suggested a regulatory role of GABA on Dopaminergic neurons. Behavioural studies in animals have provided additional interaction between GABAergic and DAergic systems. Hypofuntioning of nigrostriatal DAergic system in rats is responsible for induction of catalepsy. Haloperidol induces catalepsy in rats by blocking post synaptic striatal D2DA receptors. Hence the study was taken up to evaluate the eff...

  8. EFFECT OF PHYLLANTHUS AMARUS ON HALOPERIDOL INDUCED CATALEPSY IN EXPERIMENTAL ANIMAL MODELS

    OpenAIRE

    Deepa B; Anu E Joy; Shyamjith Manikkoth

    2015-01-01

    Objectives: The aim of the study was to investigate the anticataleptic effect of Phyllanthus amarus ethanolic extract in Swiss albino mice. Methods: The ethanolic extract of leaves of Phyllanthus amarus [PAEE] at a dose of 100mg/kg/body weight was administered orally for ten days. On tenth day, one hour later Haloperidol [1 mg/ kg IP] was administered to induce catalepsy. Results: The results indicate that induction of catalepsy by Haloperidol in Swiss albino mice was significantly prevented ...

  9. Haloperidol, but not clozapine, produces dramatic catalepsy in Δ9-THC-treated rats: possible clinical implications

    OpenAIRE

    Marchese, Giorgio; Casti, Paola; Ruiu, Stefania; Saba, Pierluigi; Sanna, Angela; Casu,Gianluca; Pani, Luca

    2003-01-01

    The effect on rat catalepsy induced by Δ9-tetrahydrocannabinol (Δ9-THC) in association with haloperidol (HP) or clozapine (CLOZ) administration was investigated.Δ9-THC dose-dependently increased HP (0.05–1 mg kg−1, s.c.)-induced rat catalepsy, while no catalepsy was observed after CLOZ (1–20 mg kg−1, s.c.) or Δ9-THC+CLOZ administration.The CB1 antagonist SR141716A (0.5–5 mg kg−1, i.p.) reversed the increase mediated by Δ9-THC on HP-induced catalepsy.The D2 agonist quinpirole completely revers...

  10. Biphasic effects of direct, but not indirect, GABA mimetics and antagonists on haloperidol-induced catalepsy.

    Science.gov (United States)

    Worms, P; Lloyd, K G

    1980-03-01

    At very low doses the GABA agonists SL 76002 and muscimol diminish haloperidol-induced catalepsy. At somewhat higher doses these compounds potentiate catalepsy. Biphasic effects on DA-receptor mediated functions have previously been noted with bicuculline and picrotoxinin. In contrast, manipulation of GABA levels by enzyme inhibition induced only a monophasic effect on dopamine-mediated behaviour. The potentiation of GABA levels by enzyme inhibition induced only a monophasic effect on dopamine-mediated behaviour. The potentiation of haloperidol-induced catalepsy by GABA mimetics is also observed with dipropylacetate, delta-aminovaleric acid and gamma-acetylenic GABA. This GABA-mimetic potentiation of catakepsy was blocked by the coadministration of bicuculline. These results confirm and extend the hypothesis that GABA-neurons influence DA neuron function. Furthermore they suggest that more than one group of GABA receptors influence directly and/or indirectly DA neuronal function, with different resultant effects. PMID:7189827

  11. The Effect of Chronic Administration of Buspirone on 6-Hydroxydopamine-Induced Catalepsy in Rats

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    Hamdolah Sharifi

    2012-06-01

    Full Text Available Purpose: Several evidences show that serotonergic neurons play a role in the regulation of movements executed by the basal ganglia. Recently we have reported that single dose of buspirone improved 6-hydroxydopamine (6-OHDA and haloperidol-induced catalepsy. This study is aimed to investigate effect of chronic intraperitoneal (i.p. administration of buspirone on 6-OHDA-induced catalepsy in male Wistar rats. Methods: Catalepsy was induced by unilateral infusion of 6-OHDA (8 μg/2 μl/rat into the central region of the SNc and was assayed by the bar-test method 5, 60, 120 and 180 min after drugs administration in 10th day. The effect of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days was assessed in 6-OHDA-lesioned rats. Results: The results showed that chronic injection of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days decreased catalepsy when compared with the control group. The best anticataleptic effect was observed at the dose of 1 mg/kg. The catalepsy-improving effect of buspirone was reversed by 1-(2-methoxyphenyl- 4-[4-(2-phthalimido butyl]piperazine hydrobromide (NAN-190, 0.5 mg/kg, i.p.,as a 5-HT1A receptor antagonist. Conclusion: Our study indicates that chronic administration of buspirone improves catalepsy in a 6-OHDA-induced animal model of parkinson's disease (PD. We also suggest that buspirone may be used as an adjuvant therapy to increase effectiveness of antiparkinsonian drugs. In order to prove this hypothesis, further clinical studies should be done.

  12. EFFECT OF PHYLLANTHUS AMARUS ON HALOPERIDOL INDUCED CATALEPSY IN EXPERIMENTAL ANIMAL MODELS

    Directory of Open Access Journals (Sweden)

    Deepa B

    2015-07-01

    Full Text Available Objectives: The aim of the study was to investigate the anticataleptic effect of Phyllanthus amarus ethanolic extract in Swiss albino mice. Methods: The ethanolic extract of leaves of Phyllanthus amarus [PAEE] at a dose of 100mg/kg/body weight was administered orally for ten days. On tenth day, one hour later Haloperidol [1 mg/ kg IP] was administered to induce catalepsy. Results: The results indicate that induction of catalepsy by Haloperidol in Swiss albino mice was significantly prevented by PAEE. Conclusions: The anticataleptic activity of Phyllanthus amarus can be due to its effect on brain neurotransmitters or due to antioxidant property.

  13. Effect of Tribulus terrestris on haloperidol-induced catalepsy in mice

    Directory of Open Access Journals (Sweden)

    B S Nishchal

    2014-01-01

    Full Text Available Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally. The first group received the vehicle (10 ml/kg, orally, the second group received trihexyphenidyl (10 mg/kg, orally and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally. The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects.

  14. Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice.

    Science.gov (United States)

    Nishchal, B S; Rai, S; Prabhu, M N; Ullal, Sheetal D; Rajeswari, S; Gopalakrishna, H N

    2014-01-01

    Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group received the vehicle (10 ml/kg, orally), the second group received trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally). The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects. PMID:25593394

  15. Study of interaction of nifedipine with haloperidol on conditioned avoidance response and catalepsy in rats

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    Nitibhushansingh R. Chandel

    2012-06-01

    Full Text Available Background: To study the interaction of calcium channel blocker (Nifedipine with Antipsychotic drug (Haloperidol on Conditioned avoidance Response and catalepsy in Rats. Methods: Every group consisted of 10 healthy albino rats of either sex. Different groups received Nifedipine (5, 10 & 20 mg/kg, i.p., Haloperidol (ED50 -0.2mg/kg for CAR & 0.4mg/kg for catalepsy alone and combined doses of both drugs. The Antipsychotic effect of drugs was measured by Conditioned avoidance response (CAR using Cook’s Pole climbing apparatus and Adverse drug effect (Extra pyramidal syndrome was measured by Catalepsy. Results: 5 mg/kg i.p. of Nifedipine inhibited CAR in 50 % of Rats (compared to control, p<0.001. 10mg/kg i.p. of Nifedipine inhibited CAR in 60% of Rats (p<0.001 & 20 mg/kg i.p. inhibited CAR in 70% of Rats (p<0.001. When Nifedipine (5 mg/kg i.p was combined with Haloperidol ED50-0.2mg/kg the CAR was inhibited in 70% of the rats (p<0.01 and after combining Nifedipine (10mg/kg with Haloperidol ED50-0.2mg/kg the CAR was inhibited in 80% Rats (p<0.001. Nifedipine at the dose of 5 mg/kg and 10 mg/kg (i.p. did not induce catalepsy in the rats at any testing time interval. At 20 mg/kg i.p., it produced catalepsy in 2 rats at half hour and in 4 rats at 1 hour and 2 hour testing interval each (p<0.01. In the dose of 5, 10 and 20 mg/kg, pretreatment with Nifedipine significantly increased Haloperidol induced cataleptic scores at all testing intervals (p<0.05. Conclusions: Nifedipine blocked CAR. Its higher doses induced catalepsy and it is synergistic with haloperidol in blockade of CAR and catalepsy. [Int J Basic Clin Pharmacol 2012; 1(3.000: 178-183

  16. Evaluation of toxicological and antioxidant potential of Nardostachys jatamansi in reversing haloperidol-induced catalepsy in rats

    OpenAIRE

    Rasheed, A S; Venkataraman, S.; K N Jayaveera; Fazil, A Mohammed; Yasodha, K J; Aleem, M A; Mohammed, M.; Khaja, Z; Ushasri, B; Pradeep, H A; Ibrahim, M.

    2010-01-01

    An aqueous root extract from Nardostachys jatamansi was investigated for its antioxidant and anticataleptic effects in the haloperidol-induced catalepsy rat model of the disease by measuring various behavioral and biochemical parameters. Catalepsy was induced by administration of haloperidol (1 mg/kg, ip) in male albino rats. A significant (P < 0.01) reduction in the cataleptic scores were observed in all the drug-treated groups as compared to the haloperidol-treated group; with maximum reduc...

  17. Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice

    OpenAIRE

    Abdel-Salam, Omar M.E.; El-Din M. Gaafar, Alaa; El Sayed El-Shamarka, Marawa; Salem, Neveen A

    2012-01-01

    Haloperidol is a classic antipsychotic drug known for its propensity to cause extrapyramidal symptoms due to blockade of dopamine D2 receptors in the striatum. Interest in medicinal uses of cannabis is growing. Cannabis sativa has been suggested as a possible adjunctive in treatment of Parkinson's disease. The present study aimed to investigate the effect of repeated administration of an extract of Cannabis sativa on catalepsy and brain oxidative stress induced by haloperidol administration i...

  18. Epilepsy and catalepsy in Anglo-American literature between romanticism and realism: Tennyson, Poe, Eliot and Collins.

    Science.gov (United States)

    Wolf, P

    2000-12-01

    Epilepsy and catalepsy were not clearly separated in the minds of people in the early 19th century, and catalepsy may have been used as a diagnostic euphemism for epilepsy. Tennyson, in "The Princess" describes, under the diagnosis of catalepsy, probable temporal lobe epileptic dreamy states with derealization which serve as a metaphor of sexual and moral ambivalence, the poem's central theme. It seems that Tennyson knew such seizures from his own father who had been given a diagnosis of catalepsy. Poe gave his Berenice in the novella of the same title a diagnosis of epilepsy as a reason for a premature burial. However, there was a good deal of unlikelyhood in this, and when he came to this theme in "The Fall of the House of Usher" and in "The Premature Burial" he chose instead a diagnosis of catalepsy which fitted better with the plot. The fits of the title character in George Eliot's Silas Marner, diagnosed as catalepsy, would today rather be seen as epileptic twilight states. It would seem that this author drew from contemporary dictionary descriptions which described conditions similar to Marner's fits under the heading of catalepsy. In Eliot's "legend with a realistic treatment", the twilight states are a central factor in the plot and explain Marner's reclusion and passivity. In Poor Miss Finch by English realist Wilkie Collins, the post-traumatic seizures of Oscar, one of the main characters, their cause, their treatment with silver nitrate, and the subsequent discoloration of his skin are central supporting elements of a perfectly constructed plot. Collins gives an exact description of a right versive seizure with secondary generalisation, and how to deal with it. In none of these works seizures are seen in a negative light. They rather evoke reactions of sympathy and support. PMID:11232370

  19. Gender-related differences in the effects of nitric oxide donors on neuroleptic-induced catalepsy in mice

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    Pires J.G.P.

    2003-01-01

    Full Text Available It has been suggested that nigrostriatal dopaminergic transmission is modulated by nitric oxide (NO. Since there is evidence that gonadal hormones can affect extrapyramidal motor behavior in mammals, we investigated the effects of isosorbide dinitrate (ISD, linsidomine (SIN-1 and S-nitroso-N-acetylpenicillamine (SNAP, three pharmacologically different NO donors, on neuroleptic-induced catalepsy in 60- to 80-day-old male and female albino mice. Catalepsy was induced with haloperidol (1 mg/kg, ip and measured at 30-min intervals by means of a bar test. Drugs (or appropriate vehicle were injected ip 30 min before haloperidol, with each animal being used only once. ISD (5, 20 and 50 mg/kg caused a dose-dependent inhibition of catalepsy in male mice (maximal effect 120 min after haloperidol: 64% inhibition. In the females only at the highest dose of ISD was an attenuation of catalepsy observed, which was mild and short lasting. SIN-1 (10 and 50 mg/kg did not significantly affect catalepsy in female mice, while a significant attenuation was observed in males at the dose of 50 mg/kg (maximal inhibition: 60%. SNAP (20 mg/kg significantly attenuated catalepsy in males 120 min after haloperidol (44% inhibition, but had no significant effect on females. These results basically agree with literature data showing that NO facilitates central dopaminergic transmission, although the mechanisms are not fully understood. They also reveal the existence of gender-related differences in this nitrergic modulation in mice, with females being less affected than males.

  20. Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

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    Sonego, Andreza B; Gomes, Felipe V; Del Bel, Elaine A; Guimaraes, Francisco S

    2016-08-01

    Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant. Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic. In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol. To further investigate this latter effect, we tested whether CBD (15-60mg/kg) would attenuate the catalepsy and c-Fos protein expression in the dorsal striatum induced by haloperidol (0.6mg/kg). We also evaluated if these effects occur through the facilitation of 5-HT1A receptor-mediated neurotransmission. For this, male Swiss mice were treated with CBD and haloperidol systemically and then subjected to the catalepsy test. Independent groups of animals were also treated with the 5-HT1A receptor antagonist WAY100635 (0.1mg/kg). As expected, haloperidol induced catalepsy throughout the experiments, an effect that was prevented by systemic CBD treatment 30min before haloperidol administration. Also, CBD, administered 2.5h after haloperidol, reversed haloperidol-induced catalepsy. Haloperidol also increased c-Fos protein expression in the dorsolateral striatum, an effect attenuated by previous CBD administration. CBD effects on catalepsy and c-Fos protein expression induced by haloperidol were blocked by the 5-HT1A receptor antagonist. We also evaluated the effects of CBD (60nmol) injection into the dorsal striatum on haloperidol-induced catalepsy. Similar to systemic administration, this treatment reduced catalepsy induced by haloperidol. Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors. PMID:27131780

  1. Comparison of isomers of ketamine on catalepsy in the rat and electrical activity of the brain and behavior in the cat.

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    Benthuysen, J L; Hance, A J; Quam, D D; Winters, W D

    1989-10-01

    The present study compared the relative potency and efficacy of the two isomers of ketamine on the duration of catalepsy (loss of righting reflex) in female rats and on the behavior and electroencephalogram of cats. In the rat, at small doses, the S(+) isomer was more potent than the R(-) isomer or racemic ketamine, while at larger doses, the S(+) isomer and the racemate were equipotent and the R(-) isomer was significantly less potent. Tolerance developed rapidly to the effects of either isomer and both were equally cross-tolerant to racemic ketamine. Sub-effective doses of morphine significantly increased the potency of S(+), R(-) and racemic ketamine on the duration of catalepsy. Sub-effective doses of either isomer augmented the duration of catalepsy, induced by small doses of morphine, but reduced that of large doses. In cats, there was a parallel time course and progression of behavioral and electroencephalographic states in response to equal total doses of either racemic ketamine, an artificial 50:50 mixture of S(+) and R(-) isomers, or the S(+) isomer alone; approximately equivalent effects required twice the dose of the R(-) isomer. It is concluded that there is a common site of action for the two isomers, but there is also a stereospecific difference in potency, as regards the induction of catalepsy in the rat and behavioral and electroencephalographic effects in the cat. Stereospecificity was not apparent in the development of tolerance, cross-tolerance or the augmentation of the response to morphine. PMID:2812279

  2. Prevention by (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin of both catalepsy and the rises in rat striatal dopamine metabolism caused by haloperidol.

    OpenAIRE

    Andersen, H. L.; Kilpatrick, I C

    1996-01-01

    1. The influence of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on haloperidol-induced increases in the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA), was measured in three microdissected brain regions of the rat following a quantitative assessment of catalepsy. 2. Haloperidol alone (2.66 mumol kg-1, i.p.) caused a robust cataleptic response. Given 30 min after haloperidol, 8-OH-DPAT (76 or 760 nmol kg-1, s.c.) prevent...

  3. Gene networks and haloperidol-induced catalepsy

    OpenAIRE

    Iancu, O. D.; Darakjian, P.; Malmanger, B.; Walter, N. A. R.; McWeeney, S.; Hitzemann, R

    2011-01-01

    The current study examined the changes in striatal gene network structure induced by short-term selective breeding from a heterogeneous stock for haloperidol response. Brain (striatum) gene expression data were obtained using the Illumina WG 8.2 array, and the datasets from responding and non-responding selected lines were independently interrogated using a weighted gene coexpression network analysis (WGCNA). We detected several gene modules (groups of coexpressed genes) in each dataset; the ...

  4. Antipsychotic-induced catalepsy is attenuated in mice lacking the M4 muscarinic acetylcholine receptor

    OpenAIRE

    Fink-Jensen, Anders; Schmidt, Lene S.; Dencker, Ditte; Schülein, Christina; Wess, Jürgen; Wörtwein, Gitta; Woldbye, David P.D.

    2011-01-01

    A delicate balance exists between the central dopaminergic and cholinergic neurotransmitter systems with respect to motor function. An imbalance can result in motor dysfunction as observed in Parkinson’s disease patients and in patients treated with antipsychotic compounds. Cholinergic receptor antagonists can alleviate extrapyramidal symptoms in Parkinson’s disease and motor side effects induced by antipsychotics. The effects of anticholinergics are mediated by muscarinic receptors of which ...

  5. Antipsychotic-induced catalepsy is attenuated in mice lacking the M4 muscarinic acetylcholine receptor

    DEFF Research Database (Denmark)

    Fink-Jensen, Anders; Schmidt, Lene S; Dencker, Ditte;

    2011-01-01

    A delicate balance exists between the central dopaminergic and cholinergic neurotransmitter systems with respect to motor function. An imbalance can result in motor dysfunction as observed in Parkinson's disease patients and in patients treated with antipsychotic compounds. Cholinergic receptor a...

  6. Radiation-induced increases in sensitivity of cataleptic behavior to haloperidol: possible involvement of prostaglandins

    International Nuclear Information System (INIS)

    The effects of radiation exposure on haloperidol-induced catalepsy were examined in order to determine whether elevated prostaglandins, through an action on dopaminergic autoreceptors, could be involved in the radiation-induced increase in the potency of this neuroleptic. Cataleptic behavior was examined in animals irradiated with various doses of gamma photons (1-150 Gy) and pretreated with a subthreshold dose of haloperidol (0.1 mg/kg). This approach was chosen to maximize any synergistic effects of radiation and haloperidol. After irradiation with doses less than or equal to 30 Gy, the combined treatment of haloperidol and radiation produced catalepsy, whereas neither treatment alone had an effect. This observed catalepsy could be blocked with prior administration of indomethacin, a prostaglandin synthesis inhibitor. Animals exposed to doses of radiation less than or equal to 50 Gy and no haloperidol, however, displayed apparent catalepsy. This effect was also antagonized by indomethacin. Prostaglandins can induce catalepsy and when administered in subthreshold doses along with subthreshold doses of haloperidol, catalepsy was observed. In order to assess a possible action of prostaglandins and radiation on dopaminergic activity, the functioning of striatal dopaminergic autoreceptors was examined by determining the effects of varying concentrations of haloperidol on the K+-evoked release of dopamine from striatal slices obtained from parallel groups of animals treated as above. Results indicated that sensitivity to haloperidol increased (higher K+-evoked dopamine release) in slices from irradiated or prostaglandin-treated animals and that this increase in sensitivity was blocked by indomethacin

  7. Psychotropic Activity of Sphaeranthus indicus Linn. In Experimental Animals

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    V J Galani

    2009-01-01

    Full Text Available Sphaeranthus indicus Linn. (Asteraceae is a branched herb with purple color flowers, distributed in wet places. The present study evaluated the neuropharmacological effects of the hydroalcoholic extract of S. indicus (SIE in rats and mice. Effect of SIE (100, 200 and 500 mg/kg, p.o. on spontaneous motor activity, pentobarbital-induced sleeping time, motor coordination, exploratory behaviour and apomorphine-induced stereotypy were investigated in mice. SIE (100, 200 and 500 mg/kg, p.o. induced catalepsy and effect of SIE on haloperidol induced catalepsy were studied in rats. The SIE showed significant reduction of spontaneous motor activity, exploratory behaviour and prolonged pentobarbital sleeping time in the mice. Neuroleptic potential of SIE was observed by the results in which SIE antagonized apomorphine-induced stereotypy in mice, produced catalepsy and potentiated haloperidol-induced catalepsy in rats. Further, SIE had no effect on motor-coordination as determined by the rota rod test. These results provide evidence that the hydroalcoholic extract of Sphaeranthus indicus may contain psychoactive substances that are sedative in nature with possible neuroleptic properties.

  8. Respiratory and locomotor stimulation by low doses of dermorphin - a Mu1-receptor mediated effect

    OpenAIRE

    Paakkari, P.; Paakkari, I.; Sirén, Anna-Leena; Feuerstein, G

    2012-01-01

    The selective opioid mu receptor agonist dermorphin increased the locomotor activity of rats dose dependently at 1 0 to 1 00 pmolfkg i.c.v. Respiratory rate, relative tidal volume and respiratory minute volume also increased unrelated to changes in locomotor activity. Higher doses, on the other hand, produced catalepsy and respiratory depression. Pretreatment of the rats with the mu,-selective antagonist naloxonazine (10 mgfkg i.v.) blocked the stimulant locomotor and respiratory effects of l...

  9. Motor activity following the administration of selective D-1 and D-2 dopaminergic drugs to normal common marmosets

    OpenAIRE

    Löschmann, P A; Smith, L A; Klaus W. Lange; Jaehnig, P.; Jenner, P.; Marsden, C. D.

    1991-01-01

    In normal common marmosets administration of the D-1/D-2 agonist apomorphine or the selective D-2 agonist quinpirole caused a dose-dependent increase in motor activity and induced stereotyped behaviour. Both the selective D-2 antagonist raclopride and the selective D-1 antagonist SCH 23390 inhibited normal locomotor activity and induced catalepsy. Quinpirole- and apomorphine-induced motor activity were potently inhibited by pretreatment with raclopride. The effects of quinpirole, but not apom...

  10. Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics

    OpenAIRE

    Chetrit, Jonathan; Ballion, Bérangère; Laquitaine, Steeve; Belujon, Pauline; Morin, Stéphanie,; Taupignon, Anne; Bioulac, Bernard; Gross, Christian E.; Benazzouz, Abdelhamid

    2009-01-01

    Background Clinical treatments with typical antipsychotic drugs (APDs) are accompanied by extrapyramidal motor side-effects (EPS) such as hypokinesia and catalepsy. As little is known about electrophysiological substrates of such motor disturbances, we investigated the effects of a typical APD, α-flupentixol, on the motor behavior and the neuronal activity of the whole basal ganglia nuclei in the rat. Methods and Findings The motor behavior was examined by the open field actimeter and the neu...

  11. Systemic administration of the neurotensin NTS1 receptor agonist PD149163 improves performance on a memory task in naturally deficient male Brown Norway rats

    OpenAIRE

    Keiser, Ashley A.; Matazel, Katelin S.; Esser, Melissa K.; Feifel, David; Prus, Adam J.

    2014-01-01

    Agonists for neurotensin NTS1 receptor consistently exhibit antipsychotic effects in animal models without producing catalepsy, suggesting that NTS1 receptor agonists may be a novel class of drugs to treat schizophrenia. Moreover, studies utilizing NTS1 agonists have reported improvements in some aspects of cognitive functioning, including prepulse inhibition and learning procedures, that suggest an ability of NTS1 receptor agonists to diminish neurocognitive deficits. The present study sough...

  12. Egg white hydrolysate promotes neuroprotection for neuropathic disorders induced by chronic exposure to low concentrations of mercury.

    Science.gov (United States)

    Rizzetti, Danize Aparecida; Fernandez, Francisca; Moreno, Silvia; Uranga Ocio, José Antonio; Peçanha, Franck Maciel; Vera, Gema; Vassallo, Dalton Valentim; Castro, Marta Miguel; Wiggers, Giulia Alessandra

    2016-09-01

    This study aims to investigate whether the egg white hydrolysate (EWH) acts on the neuropathic disorders associated with long-term Mercury (Hg) exposure in rats. 8- week-old male Wistar rats were treated for 60 days with: a) Control - saline solution (i.m.); b) Mercury - HgCl2 (1st dose 4.6μg/kg, subsequent doses 0.07μg/kg/day, i.m.); c) Hydrolysate - EWH (1g/kg/day, gavage); d) Mercury and Hydrolysate. Mechanical allodynia was assessed using Von Frey Hairs test; heat hyperalgesia by the plantar test; catalepsy by a modification of the "ring test" and spontaneous locomotor activity by a photocell activity chambers. Analyses were performed at 0, 30 and 60 days of treatment. Brain and plasma MDA, plasma NPSH and TNF-α determination and skin immunohistochemistry were performed at 60 days. Hg induced a reduction in mechanical sensitivity threshold at 30 and 60 days and in thermal sensitivity threshold at 60 days. At the end of treatment catalepsy was developed, but there was not significant alteration in spontaneous locomotor activity. Hg also increased brain and plasma MDA, plasma NPSH and TNF-α levels and the number of Merkel cell-neurite complex in the skin. EWH prevented the development of mechanical allodynia, thermal hyperalgesia and catalepsy induced by Hg and the increase in MDA concentration in brain and plasma and in the number of Merkel cell-neurite complex in the skin. In conclusion, EWH promotes neuroprotection against the toxic effects caused by Hg, demonstrating a beneficial therapeutic potential. PMID:27350078

  13. Pharmacological evaluation of bee venom and melittin

    OpenAIRE

    Camila G. Dantas; Tássia L.G.M. Nunes; Tâmara L.G.M. Nunes; Ailma O. da Paixão; Francisco P. Reis; Waldecy de L. Júnior; Juliana C. Cardoso; Kátia P. Gramacho; Gomes, Margarete Z

    2014-01-01

    The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field), catalepsy, anxiety (elevated plus-maze), depression (forced swimming test) and apomorphine-induced stereot...

  14. Psychoactive-drug response is affected by acute low-level microwave irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lai, H.; Horita, A.; Chou, C.K.; Guy, A.W.

    1983-01-01

    The effects of various psychoactive drugs were studied in rats exposed for 45 min in a circularly polarized, pulsed microwave field (2450 MHz; SAR 0.6 W/kg; 2-microseconds pulses, 500 pps). Apomorphine-induced hypothermia and stereotypy were enhanced by irradiation. Amphetamine-induced hyperthermia was attenuated while stereotypy was unaffected. Morphine-induced catalepsy and lethality were enhanced by irradiation at certain dosages of the drug. Since these drugs have different modes of action on central neural mechanisms and the effects of microwaves depend on the particular drug studied, these results show the complex nature of the effect of microwave irradiation on brain functions.

  15. EVALUATION OF ANXIOLYTIC ACTIVITY OF BOERHAAVIA DIFFUSA HYDRO-ALCOHOLIC EXTRACT OF LEAVES IN RATS

    Directory of Open Access Journals (Sweden)

    Gadekar Dayanand H.

    2011-10-01

    Full Text Available The hydro-alcoholic extract of Boerhaavia diffusa of leaves was investigated for evaluation of exhibited anxiolytic activity in rats at a dose 100 and 200 mg/kg by p.o. route for Elevated Plus Maze test, Hole Board Test, Ketamine induced Sleep and Haloperidol Induced Catalepsy method.. Results of in-vivo activity lead to the conclusion that the hydro-alcoholic of Boerhaavia diffusa showed predominantly significant activity which is compared to the standard drug Diazepam (0.5mg/kg.

  16. Preliminary screening of five ethnomedicinal plants of Guatemala.

    Science.gov (United States)

    Morales, C; Gomez-Serranillos, M P; Iglesias, I; Villar, A M; Cáceres, A

    2001-01-01

    We performed the Irwin test on some different extracts of the aerial parts of Tridax procumbens L., of the leaves of Neurolaena lobata (L.) R. Br., of the bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp. and of the root and leaves of Petiveria alliacea L. At a dosage of 1.25 g extract/100 g dried plant, the aqueous extracts of bark and leaves of Byrsonima crassifolia (L.) Kunth. and G. sepium Jacq. Walp. showed higher activity: decrease in motor activity, back tonus, reversible parpebral ptosis. catalepsy and strong hypothermia. PMID:11482789

  17. Effects of cholinoblockers on acetylcholine content in rat striatum in neuroleptic-induced parkinsonism.

    Science.gov (United States)

    Dagaev, S G; Kosmachev, A B; Soloveva, N E; Filko, O A; Sanotskii, V I; Dolgo-Saburov, V B

    2004-02-01

    Correction of neuroleptic-induced parkinsonism in rats with two central cholinoblockers atropine and pentifine (acetylene aminoalcohol synthesized at Institute of Toxicology) were studied by measuring the content of acetylcholine in the striatum. The content of the transmitter secretion was estimated from the content of bound acetylcholine fraction in homogenates of the above-mentioned compartment of the brain. The results indicate that atropine and pentifine in doses equally effectively preventing catalepsy in rats had different effects on acetylcholine secretion in the striatum. Hence, cholinolytics with different pharmacological selective effects differently interact with central muscarine receptor subtypes. PMID:15273765

  18. Anti-Parkinson Activity of Petroleum Ether Extract of Ficus religiosa (L. Leaves

    Directory of Open Access Journals (Sweden)

    Jitendra O. Bhangale

    2016-01-01

    Full Text Available In the present study, we evaluated anti-Parkinson’s activity of petroleum ether extract of Ficus religiosa (PEFRE leaves in haloperidol and 6 hydroxydopamine (6-OHDA induced experimental animal models. In this study, effects of Ficus religiosa (100, 200, and 400 mg/kg, p.o. were studied using in vivo behavioral parameters like catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters (MDA, CAT, SOD, and GSH in rats. The experiment was designed by giving haloperidol to induce catalepsy and 6-OHDA to induce Parkinson’s disease-like symptoms. The increased cataleptic scores (induced by haloperidol were significantly (p<0.001 found to be reduced, with the PEFRE at a dose of 200 and 400 mg/kg (p.o.. 6-OHDA significantly induced motor dysfunction (muscle rigidity and hypolocomotion. 6-OHDA administration showed significant increase in lipid peroxidation level and depleted superoxide dismutase, catalase, and reduced glutathione level. Daily administration of PEFRE (400 mg/kg significantly improved motor performance and also significantly attenuated oxidative damage. Thus, the study proved that Ficus religiosa treatment significantly attenuated the motor defects and also protected the brain from oxidative stress.

  19. Anti-Parkinson Activity of Petroleum Ether Extract of Ficus religiosa (L.) Leaves.

    Science.gov (United States)

    Bhangale, Jitendra O; Acharya, Sanjeev R

    2016-01-01

    In the present study, we evaluated anti-Parkinson's activity of petroleum ether extract of Ficus religiosa (PEFRE) leaves in haloperidol and 6 hydroxydopamine (6-OHDA) induced experimental animal models. In this study, effects of Ficus religiosa (100, 200, and 400 mg/kg, p.o.) were studied using in vivo behavioral parameters like catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters (MDA, CAT, SOD, and GSH) in rats. The experiment was designed by giving haloperidol to induce catalepsy and 6-OHDA to induce Parkinson's disease-like symptoms. The increased cataleptic scores (induced by haloperidol) were significantly (p < 0.001) found to be reduced, with the PEFRE at a dose of 200 and 400 mg/kg (p.o.). 6-OHDA significantly induced motor dysfunction (muscle rigidity and hypolocomotion). 6-OHDA administration showed significant increase in lipid peroxidation level and depleted superoxide dismutase, catalase, and reduced glutathione level. Daily administration of PEFRE (400 mg/kg) significantly improved motor performance and also significantly attenuated oxidative damage. Thus, the study proved that Ficus religiosa treatment significantly attenuated the motor defects and also protected the brain from oxidative stress. PMID:26884755

  20. Antipsychotic Potentials of Ocimum sanctum Leaves

    Directory of Open Access Journals (Sweden)

    Renu Kadian

    2015-01-01

    Full Text Available The present study was undertaken to evaluate the antipsychotic potential of Ocimum sanctum in experimental animal models. Male Wistar rats (180-220 g and albino mice (25-30 g were used for the study. The antipsychotic effect of the Ocimum sanctum was evaluated on haloperidol induced catalepsy, cooks pole climbing apparatus, locomotor activity on actophotometer, ketamine induced stereotype behavior. Different groups of rats were fed orally with a specially prepared diet containing various concentrations (2% w/w, 4% w/w and 8% w/w of Ocimum sanctum leaves paste (OCLP for 15 consecutive days. Further, the biochemical estimations were done by estimating brain dopamine levels. The OCLP produced significant dose dependent potentiation of haloperidol (1mg/kg, i.p. induced catalepsy in rats, significantly increased the time taken by the rat to climb the pole in dose dependent manner, significantly decreased the locomotor activity. The OCLP significantly decreased ketamine (50 mg/kg, i.p. induced stereotyped behavior in a dose dependent manner. Ocimum sanctum leaves paste (OCLP significantly decreased the brain dopamine levels. The results suggest that OCLP posse’s antipsychotic activity. Further neurochemical investigation can explore the mechanism of action of the plant drug with respect to anti-dopaminergic functions and help to establish the plant as an antipsychotic agent.

  1. Studies on sensitivity of zebrafish as a model organism for Parkinson′s disease: Comparison with rat model

    Directory of Open Access Journals (Sweden)

    Dinesh T Makhija

    2014-01-01

    Full Text Available Objective: To determine the utility of zebra fish as an animal model for Parkinson′s disease (PD in comparison with rat model. Materials and Methods: MTT assay was performed on rat and zebrafish brain synaptosomal fractions using rotenone as a neurotoxic agent. Quercetin and resveratrol were used as standards to compare anti-apoptotic activity in both organisms. Catalepsy was induced in zebrafish by exposing them to haloperidol (9 μM solution. Drug-treated groups were exposed to bromocriptine and pramipexole, 30 min prior to haloperidol exposure at the dose of 2, 5, and 10 μg/mL. Swimming speed, time spent in the bottom of the tank, and complete cataleptic time were evaluated to assess behavioral changes. In rats, catalepsy was induced using haloperidol (1.25 mg/kg i.p.. Drug-treated groups received bromocriptine (2.5 mg/kg. and pramipexole (1 mg/kg orally. Bar test, block test, and locomotor activity were carried out to assess behavioral changes. Results: Resveratrol and quercetin showed comparable inhibition of apoptosis in rats and zebrafish. In anti-cataleptic study, bromocriptine and pramipexole-treated groups showed significant difference (P < 0.05 in behavioral parameters as compared to haloperidol control group in both the experimental organisms. Results obtained from fish model were in correlation with rat model. Conclusion: Findings of the present study revealed that zebrafish model is highly sensitive and can be used for basic screening of drugs against PD.

  2. Antipsychotic-like effects of zolpidem in Wistar rats.

    Science.gov (United States)

    Mierzejewski, Pawel; Kolaczkowski, Marcin; Marcinkowska, Monika; Wesolowska, Anna; Samochowiec, Jerzy; Pawlowski, Maciej; Bienkowski, Przemyslaw

    2016-02-15

    Aside from their use in the treatment of anxiety disorders and insomnia, benzodiazepines and other GABAA receptor positive modulators are widely used as add-on treatments in schizophrenic and non-schizophrenic psychoses. However, there is relatively little direct clinical or pre-clinical evidence for antipsychotic effects of GABAergic medications. Previous studies have indicated that zolpidem, a GABAergic drug acting preferentially at α1-containing GABAA receptors, may produce catalepsy through interactions with dopaminergic neurotransmission. The aim of the present study was to investigate effects of zolpidem in experimental models of antipsychotic activity and extrapyramidal side effects in Wistar rats. Effects of zolpidem were compared with that of a classic benzodiazepine drug, diazepam and a second-generation antipsychotic medication, risperidone. High doses of risperidone (10.0mg/kg, i.p.) and zolpidem (10.0mg/kg, i.p.), but not diazepam, induced relatively short-lasting cataleptic responses in the bar test. Zolpidem and risperidone, but not diazepam, produced some antipsychotic-like effects at doses, which produced no catalepsy and did not inhibit spontaneous locomotor activity and apomorphine-induced stereotypies. The present results tend to indicate that zolpidem exerts some neuroleptic-like effects at doses, which do not produce motor side effects. Our findings may provide further rationale for the development of new subtype-selective GABAA receptor modulators for the treatment of psychotic symptoms. PMID:26825544

  3. Mast Cell Stabilizing,Antianaphylactic and Antihistaminic Activity of Coccinia grandis Fruits in Asthma

    Institute of Scientific and Technical Information of China (English)

    Dnyaneshwar J Taur; Ravindra Y Patil

    2011-01-01

    Coccinia grandis Linn(Curcubitaceae)is a climber herb cultivated throughout India.In traditional medicine fruits have been used to treat leprosy,fever,asthma,bronchitis and jaundice.In present study,ethanol extract of C.grandis fruit(ECGF)at 100,125 and 150 mg·kg-1,i.p.,was evaluated for mast cell stabilizing,antianaphylactic and antihistaminic activity using egg albumin induced mast cell degranulation in mice;passive cutaneous anaphylaxis in rats and clonidine induced catalepsy in mice respectively.ECGF at(100-150 mg·kg-1,i.p.)significantly protected egg albumin induced degranulations of mast cells and caused reduction of blue dye leakage in passive cutaneous anaphylaxis in dose dependently.The treatment ECGF also inhibited clonidine induced catalepsy in dose dependent manner.Phytochemical studies observed presence of saponin,steroids,alkaloids,flavonoids and glycosides.In conclusion ECGF possesses mast cell stabilizing;anti anaphylactic and antihistaminic potential which might be used in treatment of asthma.

  4. Evaluation of antiasthmatic activity of Cassia sophera linn

    Directory of Open Access Journals (Sweden)

    D H Nagore

    2009-01-01

    Full Text Available Cassia sophera from the family caesalpiniaceae is being used in local traditional medicine for asthma and bronchitis. Powdered leaves of C. sophera was extracted with ethanol and subjected for sequential fractionation with chloroform, ethyl acetate and ethanol respectively. Phytochemical analysis demonstrated the presence of flavonoids and antraquinone glycosides in all of the fractions. In the present study, antiasthmatic activity of parent ethanol extract and chloroform, ethyl acetate and ethanol fractions of C. sophera were evaluated. For the evaluation, carrageenan induced paw edema, histamine induced bronchoconstriction, clonidine and haloperidol induced catalepsy, milk induced leukocytosis, and eosinophilia and passive paw anaphylaxis has performed. The paw edema significantly (p< 0.05 inhibited by the parent extract, ethyl acetate, chloroform and ethanol fraction at 4th hr with the percent inhibition 54.2%, 50.4%, 44.3%, 60.7% respectively. In the present study C. sophera significantly (P< 0.05 protected the bronchoconstriction in guinea pigs against histamine-induced bronchospasm. The parent extract, ethyl acetate, chloroform and ethanol fractions showed 62.7%, 60%, 55% and 64% protection at 4th hour respectively. The clonidine induced catalepsy was found to be inhibited significantly (P< 0.05 by parent extract, ethyl acetate, chloroform and ethanol fraction at 120 min (144.00±4.830, 150.50±9.773 175.33, ±13.990, 142.50 ±4.233 sec. The parent extract, ethyl acetate, chloroform and ethanol fractions failed to revert the haloperidol induced catalepsy. In milk induced leukocytosis, milk treated group showed 4575.0 ±117.44 per cu mm leukocyte. The parent extract, ethyl acetate, chloroform and ethanol fractions reduced leukocyte count (1550.0±78.528, 2083.3±35.746, 2750.0±73.030, 1266.7±72.648 per cu mm resp. and eosinophil count (38.333±2.216, 82.333±2.1246, 2.500±1.057, 40.500±2.078 per cu mm resp. where milk treated group

  5. The pathophysiological functions mediated by D-1 dopamine receptors

    International Nuclear Information System (INIS)

    This chapter describes some behavioral responses which might be mediated by D1 and D2 DA receptors, and the authors discuss their clinical relevance. It was of considerable interest to determine whether a selective D1 DA antagonist, such as SCH 23390, will induce catalepsy and whether this behavior is mediated by D1, or by both D1 and D2 DA receptors. Rats were used in the experiments. The authors examined whether the addition of the S2 antagonist ketanserin affects the displacement of 3H-Spi by SCH 23390. Induction of self-mutilating biting (SMB) behavior in monkeys with unilateral ventromedial tegmental (VMT) lesions by DA agonists and its prevention by DA antagonists is examined. The authors also discuss the possible relationships between abnormal guanine nucleotide metabolism and dopaminergic neuronal function through the implications in LeschNyhan syndrome and in some mental disorders

  6. SYNTHESIS, COMPUTATIONAL STUDY AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF 2-[4-(2-CHLOROBENZYL/BENZOYL SUBSTITUTED PIPERAZIN-1-YL]-N-PHENYLACETAMIDE: POTENTIAL ANTIPSYCHOTICS

    Directory of Open Access Journals (Sweden)

    Tomar Amita

    2011-06-01

    Full Text Available Benzyl and benzoyl substituted acetamides have been synthesized and evaluated as potential antipsychotic agents. The target compounds (4a-b were prepared by reaction of substituted anilines with chloroacetylchloride which further treated with 2-chlorobenzyl or 2-chlorobenzoyl piperazine in presence of potassium carbonate and potassium iodide as catalyst in acetonitrile. The structures of the target compounds (4a-b were characterized on the basis of their M.P., TLC, IR and 1H-NMR data. Computational studies of target compounds (4a-b were carried out by using software programs. The target compounds showed good similarity with respect to standard drugs. The target compounds (4a-b showed inhibition of 5-HTP induced head twitches behavior and low induction of catalepsy in mice.

  7. Pharmacological evaluation of bee venom and melittin

    Directory of Open Access Journals (Sweden)

    Camila G. Dantas

    2014-01-01

    Full Text Available The objective of this study was to identify the pharmacological effects of bee venom and its major component, melittin, on the nervous system of mice. For the pharmacological analysis, mice were treated once with saline, 0.1 or 1.2 mg/kg of bee venom and 0.1 mg/kg of melittin, subcutaneously, 30 min before being submitted to behavioral tests: locomotor activity and grooming (open-field, catalepsy, anxiety (elevated plus-maze, depression (forced swimming test and apomorphine-induced stereotypy. Haloperidol, imipramine and diazepam were administered alone (positive control or as a pre-treatment (haloperidol.The bee venom reduced motor activity and promoted cataleptic effect, in a similar manner to haloperidol.These effects were decreased by the pretreatment with haloperidol. Both melittin and bee venom decreased the apomorphine-induced stereotypies. The data indicated the antipsychotic activity of bee venom and melittin in a murine model.

  8. Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics.

    Science.gov (United States)

    Huang, Ling; Zhang, Wenjun; Zhang, Xiaohua; Yin, Lei; Chen, Bangyin; Song, Jinchun

    2015-11-15

    The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A receptors, but low affinities for the 5-HT2C and histamine H1 receptors and human ether-a-go-go-related gene (hERG) channels. Furthermore, compound 29 reduced apomorphine-induced climbing and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head twitching without observable catalepsy, even at the highest dose tested. Thus, compound 29 is a promising candidate as a multi-target antipsychotic treatment. PMID:26483200

  9. Functionality of colinergic systems in rats pre-treatment with triiodothyronine

    International Nuclear Information System (INIS)

    In order to investigate the influence of experimental hiperthyroidism in the colinergic activity, rats were injected daily, during 1, 5, 19 or 20 days, with triiodothyronine (0 to 100 ug/kg, s.c.). The hiperthyroidism was evaluated by the decrease of the body weight and the increase of the body temperature and serum hormonal levels (T3). After the administration of the cholinergic agonists (pilocarpine and oxotremorine) or a anticholinesterase drug (eserine), the cholinergic behavioural and pharmacologic activity was evaluated recording the rectal temperature, locomotor activity, catalepsy, tremor and cromodacryorrhea. The results suggests that T3 pre-treatment may induce in rats changes in the functionality of the central cholinergic post-sinaptic receptors. However, the administration of this hormone does not seem to induce any alterations in the periferic cholinergic receptors, implicated in cromodacryorrhea effect. (author)

  10. Neuropharmacological profile of ethnomedicinal plants of Guatemala.

    Science.gov (United States)

    Morales Cifuentes, C; Gómez-Serranillos, M P; Iglesias, I; Villar del Fresno, A M; Morales, C; Paredes, M E; Cáceres, A

    2001-08-01

    We carried out the Irwin's test with some different extracts of the aerial parts of Thidax procumbens L., the leaves of Neurolaena lobata (L.) R. Br., bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp., and root and leaves of Petiveria alliacea L. At dosage of 1.25 g dried plant/kg weight aqueous extracts of bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp. demonstrated the most activity: decrease in motor activity, back tonus, reversible parpebral ptosis, catalepsy and strong hypothermia. These extracts of both plants were assayed for effects on CNS and they caused very significant reductions in spontaneous locomotor activity, exploratory behavior and rectal temperature and they increased the sodium pentobarbital-induced sleeping time. PMID:11448542

  11. Investigations on behavioral effects of an extract of Cannabis sativa L. in the rat.

    Science.gov (United States)

    Ferri, S; Costa, G; Murari, G; Panico, A M; Rapisarda, E; Speroni, E; Arrigo-Reina, R

    1981-01-01

    The behavioral responses of the rat to an extract of Cannabis sativa were examined after IP injection of 5, 15 and 30 mg/kg (expressed as delta 9 tetrahydrocannabinol). The lowest dose of the extract induced stereotyped behavior (rhythmic head movements, intermittent gnawing and sniffing) together with hypersensitivity to stimuli and hyperthermia. The administration of higher doses of the extract resulted, initially, in similar behavioral effects but of greater intensity, followed by a cataleptic state alternating with atonic muscular prostration; rectal temperature was decreased. Pre-treatment with 6-hydoxydopamine (6-OHDA, which produces degeneration of catecholamine-containing nerve terminals)or pimozide (blocker of dopamine receptors) significantly reduced both stereotype and hyperreactivity. Thermic effects were also antagonized by 6-OHDA pre-treatment. Cannabis-induced catalepsy was enhanced by pimozide but reduced by atropine (3 mg/kg SC). These results support the hypothesis that catecholamines play an important role in the complex behavioral effects of cannabis. PMID:6798604

  12. Effects of age on behavioral and physiological responses to carbaryl in rats.

    Science.gov (United States)

    Takahashi, R N; Poli, A; Morato, G S; Lima, T C; Zanin, M

    1991-01-01

    Motor, sensory and thermoregulatory functions were examined in young (3 months) and mature (12 months) rats following PO administration of single low doses (10 and 50 mg/kg) of carbaryl, a carbamate insecticide, and these effects were related to blood cholinesterase activity. Carbaryl 50 mg/kg decreased the frequency of ambulation in the open-field arena within 30 min while it enhanced the duration of haloperidol-induced catalepsy in both young and mature rats. Administration of carbaryl also resulted in an increased nociceptive threshold to thermic stimuli mainly in mature rats. An age-related reduction in body temperature was observed at 30, 60 and 90 min after injection. Activity of blood cholinesterase was reduced in young and mature rats at 30 and 60 min following carbaryl exposure. These results indicate that carbaryl can induce an age-related impairment on some behavioral and autonomic functions in rats correlated to the inhibition of cholinesterase activity. PMID:1904531

  13. Differential control of dopamine ascending pathways by serotonin2B receptor antagonists: New opportunities for the treatment of schizophrenia.

    Science.gov (United States)

    Devroye, Céline; Cathala, Adeline; Haddjeri, Nasser; Rovera, Renaud; Vallée, Monique; Drago, Filippo; Piazza, Pier Vincenzo; Spampinato, Umberto

    2016-10-01

    Recent studies suggest that the central serotonin2B receptor (5-HT2BR) could be an interesting pharmacological target for treating neuropsychiatric disorders related to dopamine (DA) dysfunction, such as schizophrenia. Thus, the present study was aimed at characterizing the role of 5-HT2BRs in the control of ascending DA pathway activity. Using neurochemical, electrophysiological and behavioral approaches, we assessed the effects of two selective 5-HT2BR antagonists, RS 127445 and LY 266097, on in vivo DA outflow in DA-innervated regions, on mesencephalic DA neuronal firing, as well as in behavioral tests predictive of antipsychotic efficacy and tolerability, such as phencyclidine (PCP)-induced deficit in novel object recognition (NOR) test, PCP-induced hyperlocomotion and catalepsy. Both RS 127445 (0.16 mg/kg, i.p.) and LY 266097 (0.63 mg/kg, i.p.) increased DA outflow in the medial prefrontal cortex (mPFC). RS 127445, devoid of effect in the striatum, decreased DA outflow in the nucleus accumbens, and potentiated haloperidol (0.1 mg/kg, s.c.)-induced increase in mPFC DA outflow. Also, RS 127445 decreased the firing rate of DA neurons in the ventral tegmental area, but had no effect in the substantia nigra pars compacta. Finally, both RS 127445 and LY 266097 reversed PCP-induced deficit in NOR test, and reduced PCP-induced hyperlocomotion, without inducing catalepsy. These results demonstrate that 5-HT2BRs exert a differential control on DA pathway activity, and suggest that 5-HT2BR antagonists could represent a new class of drugs for improved treatment of schizophrenia, with an ideal profile of effects expected to alleviate cognitive and positive symptoms, without eliciting extrapyramidal symptoms. PMID:27260325

  14. The preferential nNOS inhibitor 7-nitroindazole and the non-selective one N(G)-nitro-L-arginine methyl ester administered alone or jointly with L-DOPA differentially affect motor behavior and monoamine metabolism in sham-operated and 6-OHDA-lesioned rats.

    Science.gov (United States)

    Czarnecka, Anna; Konieczny, Jolanta; Lenda, Tomasz; Lorenc-Koci, Elżbieta

    2015-11-01

    Reciprocal interactions between nitrergic and dopaminergic systems play a key role in the control of motor behavior. In the present study, we performed a comparative analysis of motor behavior (locomotor activity, catalepsy, rotational behavior) and monoamine metabolism in the striatum and substantia nigra of unilaterally sham-operated and 6-OHDA-lesioned rats treated with the preferential neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI) or the non-selective one N(G)-nitro-L-arginine methyl ester (L-NAME), alone or in combination with L-DOPA. Each NOS inhibitor given alone (50mg/kg) induced a distinct catalepsy 30 min after injection but only 7-NI impaired spontaneous locomotion after 10 min. In 6-OHDA-lesioned rats, chronic L-DOPA (25mg/kg) induced 2.5-h long contralateral rotations. 7-NI (30 and 50mg/kg) markedly reduced the intensity of L-DOPA-induced contralateral rotations while extending their duration until 4.5h whereas L-NAME (50 and 100mg/kg) only tended to attenuate their intensity without affecting the duration. 7-NI but not L-NAME significantly increased endogenous tissue DA levels in the nigrostriatal system of both sham-operated and 6-OHDA-lesioned rats. In L-DOPA-treated group, 7-NI significantly enhanced the L-DOPA-derived tissue DA content in this system and decreased the level of the intracellular DA metabolite DOPAC produced by monoamine oxidase (MAO). In contrast to 7-NI, L-NAME decreased markedly DA content and did not affect DOPAC level in the ipsilateral striatum. It means that the differences in 7-NI and L-NAME-mediated modulation of L-DOPA-induced behavioral and biochemical effects resulted not only from the inhibition of NOS activity but also from differences in their ability to inhibit MAO. PMID:26319690

  15. Dopaminergic profile of new heterocyclic N-phenylpiperazine derivatives

    Directory of Open Access Journals (Sweden)

    G. Neves

    2003-05-01

    Full Text Available Dopamine constitutes about 80% of the content of central catecholamines and has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to report the structural design of two N-phenylpiperazine derivatives, compound 4: 1-[1-(4-chlorophenyl-1H-4-pyrazolylmethyl]-4-phenylhexahydropyrazine and compound 5: 1-[1-(4-chlorophenyl-1H-1,2,3-triazol-4-ylmethyl]-4-phenylhexahydropyrazine, planned to be dopamine ligands, and their dopaminergic action profile. The two compounds were assayed (dose range of 15-40 mg/kg in three experimental models: 1 blockade of amphetamine (30 mg/kg, ip-induced stereotypy in rats; 2 the catalepsy test in mice, and 3 apomorphine (1 mg/kg, ip-induced hypothermia in mice. Both derivatives induced cataleptic behavior (40 mg/kg, ip and a hypothermic response (30 mg/kg, ip which was not prevented by haloperidol (0.5 mg/kg, ip. Compound 5 (30 mg/kg, ip also presented a synergistic hypothermic effect with apomorphine (1 mg/kg, ip. Only compound 4 (30 mg/kg, ip significantly blocked the amphetamine-induced stereotypy in rats. The N-phenylpiperazine derivatives 4 and 5 seem to have a peculiar profile of action on dopaminergic functions. On the basis of the results of catalepsy and amphetamine-induced stereotypy, the compounds demonstrated an inhibitory effect on dopaminergic behaviors. However, their hypothermic effect is compatible with the stimulation of dopaminergic function which seems not to be mediated by D2/D3 receptors.

  16. Neuroprotective potential of Beta vulgaris L. in Parkinson′s disease

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    Vandana S Nade

    2015-01-01

    Full Text Available Objective: The objective was to investigate the neuroprotective role of Beta vulgaris in Parkinson′s disease (PD. Materials and Methods: PD was induced by administration of reserpine (5 mg/kg/day, i.p for 5 consecutive days, haloperidol (1 mg/kg, i.p., and tacrine (2.5 mg/kg, i.p. in experimental animals. The symptoms of PD such as tremors, akinesia, rigidity, catalepsy, and vacuous chewing movements (VCMs were evaluated. Foot shock-induced aggression (FSIA model was used to confirm anti-parkinsonian activity. The methanolic extract of Beta vulgaris (MEBV was administered at doses of 100, 200, and 300 mg/kg, p.o. The combination of L-dopa and carbidopa was used as a standard drug. Behavioral studies such as locomotor activity and grip strength were determined, and oxidative stress was evaluated in FSIA model in rat brain. Results: Pretreatment with MEBV (200 and 300 mg/kg significantly reduced the intensity of muscular rigidity, duration of catalepsy, akinesia, the number of tremors, VCMs, and increase fighting behavior. The locomotor activity and grip strength were significantly increased by MEBV. In FSIA, the biochemical analysis of brain revealed the increased level of lipid peroxidation (LPO and decreased levels of superoxide dismutase (SOD and catalase (CAT. MEBV significantly reduced LPO level and restored the defensive antioxidant enzymes SOD and CAT in rat brain. Conclusions: The results indicated the protective role of B. vulgaris against PD. The mechanism of protection may be due to augmentation of cellular antioxidants.

  17. Antipsychotic, antidepressant, and cognitive-impairment properties of antipsychotics: rat profile and implications for behavioral and psychological symptoms of dementia.

    Science.gov (United States)

    Kołaczkowski, Marcin; Mierzejewski, Paweł; Bienkowski, Przemyslaw; Wesołowska, Anna; Newman-Tancredi, Adrian

    2014-06-01

    Many dementia patients exhibit behavioral and psychological symptoms (BPSD), including psychosis and depression. Although antipsychotics are frequently prescribed off-label, they can have marked side effects. In addition, comparative preclinical studies of their effects are surprisingly scarce, and strategies for discovery of novel pharmacotherapeutics are lacking. We therefore compared eight antipsychotics in rat behavioral tests of psychosis, antidepressant-like activity, and cognitive impairment as a basis for preclinical evaluation of new drug candidates. The methods used in this study include inhibition of MK-801-induced hyperactivity, forced swim test (FST), passive avoidance (PA), spontaneous locomotor activity, and catalepsy. The drugs exhibited antipsychotic-like activity in the MK-801 test but with diverse profiles in the other models. Risperidone impaired PA performance, but with some dose separation versus its actions in the MK-801 test. In contrast, clozapine, olanzapine, lurasidone, and asenapine showed little or no dose separation in these tests. Aripiprazole did not impair PA performance but was poorly active in the MK-801 test. Diverse effects were also observed in the FST: chlorpromazine was inactive and most other drugs reduced immobility over narrow dose ranges, whereas clozapine reduced immobility over a wider dose range, overlapping with antipsychotic activity. Although the propensity of second-generation antipsychotics to produce catalepsy was lower, they all elicited pronounced sedation. Consistent with clinical data, most currently available second-generation antipsychotics induced cognitive and motor side effects with little separation from therapeutic-like doses. This study provides a uniform in vivo comparative basis on which to evaluate future early-stage drug candidates intended for potential pharmacotherapy of BPSD. PMID:24599316

  18. Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography

    International Nuclear Information System (INIS)

    Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with 3diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with [3H]naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC50's against [3H]naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of [18F]-6 was developed and the tissue distribution of [18F]-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to 18F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned. (author)

  19. Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Dahren Hwang; Feliu, A.L.; Wolf, A.P.; MacGregor, R.R.; Fowler, J.S.; Arnett, C.D.

    1986-03-01

    Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with /sup 3/diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with (/sup 3/H)naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC/sub 50/'s against (/sup 3/H)naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of (/sup 18/F)-6 was developed and the tissue distribution of (/sup 18/F)-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to /sup 18/F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned.

  20. Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, DeltaFosB expression, and conditioned place preference to amphetamine and cocaine.

    Science.gov (United States)

    Marazziti, Daniela; Di Pietro, Chiara; Mandillo, Silvia; Golini, Elisabetta; Matteoni, Rafaele; Tocchini-Valentini, Glauco P

    2011-06-01

    The orphan G-protein-coupled receptor 37 (GPR37) colocalizes with the dopamine (DA) transporter (DAT) in mouse nigrostriatal presynaptic membranes, and its genetic ablation in homozygous null-mutant (GPR37-KO) mice provokes the marked increase of plasma membrane expression of DAT, alteration of psychostimulant-induced locomotor activity, and reduction of catalepsy induced by DA-receptor antagonists. We report that extracts from GPR37-KO mice displayed biochemical alterations of the nigrostriatal signaling pathways mediated by D1 and D2 dopaminergic receptors. Null-mutant mice showed an increase of the basal phosphorylation level of the D2-regulated Akt kinase. The basal phosphorylation of the D1-activated ERK2 kinase was not altered, but acute treatments with amphetamine or cocaine failed to produce its specific increase, as detected in samples from wild-type littermates. Furthermore, the chronic administration of cocaine to GPR37-KO mice did not increase the expression of the ΔFosB transcription factor isoforms. Consistently, behavioral analysis showed that null-mutant animals did not respond to the incentive properties of amphetamine or cocaine, in conditioned place preference tests. Thus, the lack of GPR37 affects both ERK2- and Akt-mediated striatal signaling pathways, impairing the biochemical and behavioral responses typically induced by acute and chronic administration of psychostimulant drugs. PMID:21372109

  1. 2-Aminopyrimidines as dual adenosine A1/A2A antagonists.

    Science.gov (United States)

    Robinson, Sarel J; Petzer, Jacobus P; Terre'Blanche, Gisella; Petzer, Anél; van der Walt, Mietha M; Bergh, Jacobus J; Lourens, Anna C U

    2015-11-01

    In this study thirteen 2-aminopyrimidine derivatives were synthesised and screened as potential antagonists of adenosine A1 and A2A receptors in order to further investigate the structure activity relationships of this class of compounds. 4-(5-Methylfuran-2-yl)-6-[3-(piperidine-1-carbonyl)phenyl]pyrimidin-2-amine (8m) was identified as a compound with high affinities for both receptors, with an A2AKi value of 6.34 nM and an A1Ki value of 9.54 nM. The effect of selected compounds on the viability of cultured cells was assessed and preliminary results indicate low cytotoxicity. In vivo efficacy at A2A receptors was illustrated for compounds 8k and 8m since these compounds attenuated haloperidol-induced catalepsy in rats. A molecular docking study revealed that the interactions between the synthesised compounds and the adenosine A2A binding site most likely involve Phe168 and Asn253, interactions which are similar for structurally related adenosine A2A receptor antagonists. PMID:26462195

  2. Safety and side effects of cannabidiol, a Cannabis sativa constituent.

    Science.gov (United States)

    Bergamaschi, Mateus Machado; Queiroz, Regina Helena Costa; Zuardi, Antonio Waldo; Crippa, José Alexandre S

    2011-09-01

    Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects. PMID:22129319

  3. Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain.

    Science.gov (United States)

    Seltzman, Herbert H; Shiner, Craig; Hirt, Erin E; Gilliam, Anne F; Thomas, Brian F; Maitra, Rangan; Snyder, Rod; Black, Sherry L; Patel, Purvi R; Mulpuri, Yatendra; Spigelman, Igor

    2016-08-25

    Alleviation of neuropathic pain by cannabinoids is limited by their central nervous system (CNS) side effects. Indole and indene compounds were engineered for high hCB1R affinity, peripheral selectivity, metabolic stability, and in vivo efficacy. An epithelial cell line assay identified candidates with <1% blood-brain barrier penetration for testing in a rat neuropathy induced by unilateral sciatic nerve entrapment (SNE). The SNE-induced mechanical allodynia was reversibly suppressed, partially or completely, after intraperitoneal or oral administration of several indenes. At doses that relieve neuropathy symptoms, the indenes completely lacked, while the brain-permeant CB1R agonist HU-210 (1) exhibited strong CNS side effects, in catalepsy, hypothermia, and motor incoordination assays. Pharmacokinetic findings of ∼0.001 cerebrospinal fluid:plasma ratio further supported limited CNS penetration. Pretreatment with selective CB1R or CB2R blockers suggested mainly CB1R contribution to an indene's antiallodynic effects. Therefore, this class of CB1R agonists holds promise as a viable treatment for neuropathic pain. PMID:27482723

  4. Animal models for predicting the efficacy and side effects of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Pedro H. Gobira

    2013-01-01

    Full Text Available The use of antipsychotic drugs represents an important approach for the treatment of schizophrenia. However, their efficacy is limited to certain symptoms of this disorder, and they induce serious side effects. As a result, there is a strong demand for the development of new drugs, which depends on reliable animal models for pharmacological characterization. The present review discusses the face, construct, and predictive validity of classical animal models for studying the efficacy and side effects of compounds for the treatment of schizophrenia. These models are based on the properties of antipsychotics to impair the conditioned avoidance response and reverse certain behavioral changes induced by psychotomimetic drugs, such as stereotypies, hyperlocomotion, and deficit in prepulse inhibition of the startle response. Other tests, which are not specific to schizophrenia, may predict drug effects on negative and cognitive symptoms, such as deficits in social interaction and memory impairment. Regarding motor side effects, the catalepsy test predicts the liability of a drug to induce Parkinson-like syndrome, whereas vacuous chewing movements predict the liability to induce dyskinesia after chronic treatment. Despite certain limitations, these models may contribute to the development of more safe and efficacious antipsychotic drugs.

  5. Dopamine-glutamate interactions in the basal ganglia.

    Science.gov (United States)

    Schmidt, W J

    1998-01-01

    In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of "wanted" and in the suppression of "unwanted" behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill similar functions: It may mediate reinforcement which strengthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia. Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subthalamic neurons is critically involved in basal ganglia functions and dysfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an essential factor in the plasticity response of the basal-ganglia. However, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant- nor morphine-induced day to day increase (sensitization) of locomotion. Also the day to day increase of haloperidol-induced catalepsy was not prevented by MK-801. PMID:9871434

  6. Neuroprotective effect of EGb761® and low-dose whole-body γ-irradiation in a rat model of Parkinson's disease.

    Science.gov (United States)

    El-Ghazaly, Mona A; Sadik, Nermin A H; Rashed, Engy R; Abd-El-Fattah, Amal A

    2015-12-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The present study was undertaken to investigate the pretreatment effects of standardized Ginkgo biloba extract (EGb761(®)) and low-dose whole-body γ-irradiation on the neurological dysfunction in the reserpine model of PD. Male Wistar rats were pretreated orally with EGb761 or fractionated low-dose whole-body γ-irradiation or their combination, then subjected to intraperitoneal injection of reserpine (5 mg/kg body weight) 24 h after the final dose of EGb761 or radiation. Reserpine injection resulted in the depletion of striatal dopamine (DA) level, increased catalepsy score, increased oxidative stress indicated via depletion of glutathione (GSH), increased malondialdehyde (MDA) and iron levels, decreased DA metabolites metabolizing enzymes; indicated by inhibition by glutathione-S-transferase, and nicotinamide adenine dinucleotide phosphate (NADPH)-quinone oxidoreductase (NQO) activities, mitochondrial dysfunction; indicated by declined complex I activity, and adenosine triphosphate (ATP) level and increased apoptosis; indicated by decreased mitochondrial B cell lymphoma-2 (Bcl-2) protein level and by transmission electron microscope. EGb761 and low-dose γ-radiation ameliorated the reserpine-induced state of oxidative stress, mitochondrial dysfunction, and apoptosis in brain. It can be concluded that EGb761, a widely used herbal medicine and low dose of γ-irradiation have protective effects for combating Parkinsonism possibly via replenishment of GSH levels. PMID:23696346

  7. Antinociceptive Activity of Trichilia catigua Hydroalcoholic Extract: New Evidence on Its Dopaminergic Effects

    Directory of Open Access Journals (Sweden)

    Alice F. Viana

    2011-01-01

    Full Text Available Trichilia catigua is a native plant of Brazil; its barks are used by some local pharmaceutical companies to prepare tonic drinks, such as Catuama. The present study was addressed to evaluate the effects of T. catigua hydroalcoholic extract in mouse nociception behavioral models, and to evaluate the possible mechanisms involved in its actions. Male Swiss mice were submitted to hot-plate, writhing and von Frey tests, after oral treatment with T. catigua extract (200 mg kg−1, p.o.. The extract displayed antinociceptive effect in all three models. For characterization of the mechanisms involved in the antinociceptive action of the extract, the following pharmacological treatments were done: naloxone (2.5 mg kg−1, s.c., SR141716A (10 mg kg−1, i.p., SCH23390 (15 μg kg−1, i.p., sulpiride (50 mg kg−1, i.p., prazosin (1 mg kg−1, i.p., bicuculline (1 mg kg−1, i.p. or dl-p-chlorophenylalanine methyl ester (PCPA, 100 mg kg−1, i.p.. In these experiments, the action of T. catigua extract was evaluated in the hot-plate test. The treatment with SCH23390 completely prevented the antinociceptive effect, while naloxone partially prevented it. The possible involvement of the dopaminergic system in the actions of T. catigua extract was substantiated by data showing the potentiation of apomorphine-induced hypothermia and by the prevention of haloperidol-induced catalepsy. In conclusion, the antinociceptive effects of T. catigua extract seem to be mainly associated with the activation of dopaminergic system and, to a lesser extent, through interaction with opioid pathway.

  8. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Nicolas Maurice

    Full Text Available Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD. Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure in pharmacological (neuroleptic treatment and lesional (unilateral intranigral 6-hydroxydopamine injection PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease.

  9. Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin.

    Science.gov (United States)

    Tatara, Ayaka; Shimizu, Saki; Masui, Atsushi; Tamura, Miyuki; Minamimoto, Shoko; Mizuguchi, Yuto; Ochiai, Midori; Mizobe, Yusuke; Ohno, Yukihiro

    2015-11-01

    Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin. PMID:26363311

  10. Pharmacological and chemical screening of Byrsonima crassifolia, a medicinal tree from Mexico. Part I.

    Science.gov (United States)

    Béjar, E; Malone, M H

    1993-06-01

    Leaf and bark extracts of Byrsonima crassifolia displayed concentration-dependent, spasmogenic effects on rat fundus in vitro and biphasic effects on rat jejunum and ileum in vitro. Dose-related in vivo effects in intact rats using hippocratic screening were: decrease in motor activity, mild analgesia, back tonus, enophthalmos, reversible palpebral ptosis, ear blanching, Robichaud positive, catalepsy (awake) and strong hypothermia. Rat fundus in vitro was used as the bioassay to carry out an activity-directed separation. Bioactive material was concentrated in a 2% acetic acid leaf extract (HOAcE). Potency of HOAcE was increased by the presence of pargyline in the bathing solution. HOAcE was antagonized noncompetively by 1(1-naphthyl) piperazine (1-NP) and cyproheptadine and antagonized competitively by atropine (ATR). Cumulative concentration-response curves of HOAcE and serotonin (5-HT) did not show significant departure from parallelism (P > 0.1) and 5-HT potency was 6040 times that of HOAcE (95% confidence limits: 4620-7850). Solvent extraction of HOAcE split the spasmogenic activity of HOAcE into two types: (i) high-efficacy, low-potency, n-butanol-extracted, pargyline- and 1-NP-sensitive, ATR-insensitive activity, and (ii) low-efficacy, high-potency, ethyl acetate-extracted, pargyline-insensitive, ATR- and 1-NP-sensitive activity. HOAcE lacked muscarinic and nicotinic effects on rat jejunum and frog rectus abdominis. Results suggest the presence of more than one spasmogenic compound in the plant. PMID:8412247

  11. Antiasthmatic and antiallergic potential of methanolic extract of leaves of Ailanthus excelsa

    Directory of Open Access Journals (Sweden)

    Dinesh Kumar

    2011-02-01

    Full Text Available The aim of study was antiasthmatic potential of methanolic extract of leaves of Ailanthus excelsa Roxb., Simaroubaceae. Traditionally or in Indian system of medicine, A. excelsa is used in the treatment of asthma, cough, colic pain, cancer, diabetes and also used as antispasmodic, antifertility, bronchodilator. Stem bark of A. excelsa already reported for its potential against asthma. The pollens of Ailanthus excelsa reported allergic in nature and the time of collection of leaves were important in this study, generally the flowering stage of plant was avoided for the collection due to maximum chance of pollens at that time. Methanolic extract of leaves of A. excelsa was evaluated using in vitro goat tracheal chain preparation model and in vivo- Milk induced leucocytosis, eosinophilia, Clonidine induced catalepsy in mice model while Passive paw anaphylaxis and Clonidine induced mast cell degranulation in rat model. The extract showed the presence of flavonoids, terpenoids, saponins, quassonoids and test was also positive for alkaloids and steroids. The extract also showed the presence of quercetin which is flavonoid and detected on the preparative TLC plate with the help of standard quercetin. Dose response studies of methanolic extract of leaves of A. excelsa Roxb. were conducted at 100 µg mL-1 in vitro and 100, 200, 400 mg kg-1 p.o. in vivo models. The treatment with methanolic extract of A. excelsa at different dose level showed the significant (*p<0.05, **p<0.01, ***p<0.001 antiasthmatic activity. Inhibition or decrease the release of inflammatory mediators potentiates the antiasthmatic as well as antiallergic activity of methanolic extract of leaves of A. excelsa.

  12. Aripiprazole (Otsuka Pharmaceutical Co).

    Science.gov (United States)

    Ozdemir, Vural; Fourie, Jeanne; Ozdener, Fatih

    2002-01-01

    Otsuka Pharmaceuticals in collaboration with Bristol-Myers Squibb is developing aripiprazole, a dual dopamine autoreceptor agonist and postsynaptic D2 receptor antagonist, for the potential treatment of psychoses including schizophrenia [281327], [340364]. A regulatory filing for schizophrenia in the US was submitted at the end of 2001 [340364]. The compound entered phase III trials in Japan in 1995 [192966]. Although presynaptic dopamine autoreceptor agonists may be efficacious in the treatment of schizophrenia, they may also potentially increase the risk for exacerbation of psychosis through stimulation of postsynaptic dopaminergic receptors [245791], [350478], [350479]. However, earlier neuropharmacology studies have shown that aripiprazole can act as a presynaptic D2 agonist while displaying an antagonistic effect at the postsynaptic D2 receptors [281327], [337126], [350479], [424587], [424588]. In animal models, aripiprazole inhibits the apomorphine-induced stereotypy, without causing catalepsy [281327], [337126]. Moreover, in contrast to classical antipsychotics that produce disabling movement disorders, aripiprazole does not cause an upregulation of D2 receptors or an increase in expression of the c-fos mRNA in the striatum, in agreement with the low risk for extrapyramidal side effects (EPS) during aripiprazole treatment [245781], [262096], [350481], [350483]. Collectively, aripiprazole is an important atypical antipsychotic candidate with a favorable safety profile. Moreover, the mechanism of action of aripiprazole differentiates it from both typical and atypical antipsychotics and hence, may provide important leads for pharmacotherapy of schizophrenia and other psychotic disorders. In January 2000, Lehman Brothers predicted peak sales of aripiprazole could reach US $500 million [357788]. In February 2001, Credit Suisse First Boston predicted sales of US $403 million in 2005 [399484]. PMID:12054061

  13. Prenatal exposure to integerrimine N-oxide enriched butanolic residue from Senecio brasiliensis affects behavior and striatal neurotransmitter levels of rats in adulthood.

    Science.gov (United States)

    Sandini, Thaísa M; Udo, Mariana S B; Reis-Silva, Thiago M; Sanches, Daniel; Bernardi, Maria Martha; Flório, Jorge Camilo; Spinosa, Helenice de S

    2015-12-01

    Pyrrolizidine alkaloids (PAs) are toxins that are exclusively biosynthesized by plants and are commonly present in foods and herbs. PAs are usually associated with poisoning events in livestock and human beings. The aim of the present study was to evaluate the behavioral and neurochemical effects of prenatal exposure to PA integerrimine N-oxide of rats in adulthood. Pregnant Wistar rats received integerrimine N-oxide from the butanolic residue of Senecio brasiliensis by gavage on gestational days 6-20 at doses of 3, 6 and 9 mg/kg. During adulthood of the offspring, the following behavioral tests were performed: open-field, plus-maze, forced swimming, catalepsy and stereotypy. Histological analyses and monoamine levels were measured. Male offspring from dams that were exposed to 9 mg/kg showed an increase in locomotion in the open-field test, an increased frequency of entries and time spent in open arms in elevated plus-maze test, as well as decreased swimming time. In the female offspring from dams that were exposed to 9 mg/kg, there was an increased time of climbing in forced swimming and intensity of stereotyped behavior. The histological study indicates an increase in the number of multinucleated cells in the liver (6 and 9 mg/kg). In neurotransmitter analysis, specifically in the striatum, we observed change in dopamine and serotonin levels in the middle dose. Thus, our results indicate that prenatal exposure to integerrimine N-oxide changed behavior in adulthood and neurotransmitter levels in the striatum. Our results agree with previous studies, which showed that integerrimine N-oxide impaired physical and neurobehavioral development in childhood that can persist until adulthood. PMID:26416213

  14. Evaluation of anti-parkinson’s activity of gentisic acid in different animal models

    Institute of Scientific and Technical Information of China (English)

    Kabra MP; Bhandari SS; Sharma A; Gupta RB

    2014-01-01

    Objective:To evaluate the neuroprotective activity ofGentisic acid inPD.The study was conducted on swiss albinFo mice(20-25 g) & wistar rats(200-250 g).Methods:Three behavioural models namely,Haloperidol induced catalepsy,Reserpine antagonism andHaloperidol induce orofacial dyskinesia were employed in this study,SwissAlbino mice(20-25 g) were used in first two models whileWistar rats(200-250 g) used in last one model.There are five group(n=6) in each animal model.Various behavior activity/parameter(cataleptic behavior, horizontal movements, rearing & grooming frequencies andDyskinesia activity like vacuous chewing & tongue protrusion) in different animal models were used to evaluate the anti-Parkinson’s activity ofGentisic acid.Results:Gentisic acid showed a significant(P<0.01) reduction in the duration of cataleptic behavior dose dependently when compared to haloperidol control group.Gentisic acid shows dose dependant increase in the frequency of horizontal movement and rearing behavior when compared to theReserpine control group.But, the effect ofGentisic acid on the frequency of grooming behavior was found to be insignificant.Gentisic acid(80 mg/kg) showed a significant (P<0.05) decrease in the frequency of vacuous chewing & tongue protrusion but the other dose tested were found to be insignificant in this respect.Conclusions:Results shows that the Gentisic acid produced dose dependent neuroprotective activity in different animal models ofPD.

  15. Biochemical and behavioral effects of PDE10A inhibitors: Relationship to target site occupancy.

    Science.gov (United States)

    Li, Yu-Wen; Seager, Matthew A; Wojcik, Trevor; Heman, Karen; Molski, Thaddeus F; Fernandes, Alda; Langdon, Shaun; Pendri, Annapurna; Gerritz, Samuel; Tian, Yuan; Hong, Yang; Gallagher, Lizbeth; Merritt, James R; Zhang, Chongwu; Westphal, Ryan; Zaczek, Robert; Macor, John E; Bronson, Joanne J; Lodge, Nicholas J

    2016-03-01

    Phosphodiesterase 10A (PDE10A) inhibitors increase the functionality of striatal medium spiny neurons and produce antipsychotic-like effects in rodents by blocking PDE10A mediated hydrolysis of cAMP and/or cGMP. In the current study, we characterized a radiolabeled PDE10A inhibitor, [(3)H]BMS-843496, and developed an ex vivo PDE10 binding autoradiographic assay to explore the relationship between PDE10 binding site occupancy and the observed biochemical and behavioral effects of PDE10 inhibitors in mice. [(3)H]BMS-843496 is a potent PDE10A inhibitor with a binding affinity (KD) of 0.15 nM and a functional selectivity of >100-fold over other PDE subtypes tested. Specific [(3)H]BMS-843496 binding sites were dominant in the basal ganglia, especially the striatum, with low to moderate binding in the cortical and hippocampal areas, of the mouse and monkey brain. Systemic administration of PDE10 inhibitors produced a dose- and plasma/brain concentration-dependent increase in PDE10A occupancy measured in the striatum. PDE10A occupancy was positively correlated with striatal pCREB expression levels. PDE10A occupancy was also correlated with antipsychotic-like effects measured using the conditioned avoidance response model; a minimum of ∼40% occupancy was typically required to achieve efficacy. In contrast, a clear relationship between PDE10A occupancy and catalepsy scores, a potential extrapyramidal symptom readout in rodent, was not evident. PMID:26522433

  16. Evaluation of agonist-antagonist properties of nitrogen mustard and cyano derivatives of delta 8-tetrahydrocannabinol.

    Science.gov (United States)

    Wiley, J L; Compton, D R; Gordon, P M; Siegel, C; Singer, M; Dutta, A; Lichtman, A H; Balster, R L; Razdan, R K; Martin, B R

    1996-01-01

    delta 8-Tetrahydrocannabinol (delta 8-THC) is a naturally occurring cannabinoid with a characteristic pharmacological profile of in vivo effects. Previous studies have shown that modification of the structure of delta 8-THC by inclusion of a nitrogen-containing functional group alters this profile and may alkylate the cannabinoid receptor, similar to the manner in which beta-funaltrexamine (beta-FNA) alkylates the micro-opioid receptor. Two novel analogs of delta 8-THC were synthesized: a nitrogen mustard analog with a dimethylheptyl side chain (NM-delta 8-THC) and a cyano analog with a dimethylpentyl side chain (CY-delta 8-THC). Both analogs showed high affinity for brain cannabinoid receptors and when administered acutely, produced characteristic delta 9-THC-like effects in mice, including locomotor suppression, hypothermia, antinociception and catalepsy. CY-delta 8-THC shared discriminative stimulus effects with CP 55,940; for NM-delta 8-THC, these effects also occurred, but were delayed. Although both compounds attenuated the effects of delta 9-THC in the mouse behavioral tests, evaluation of potential antagonist effects of these compounds was complicated by the fact that two injections of delta 9-THC produced similar results, suggesting that acute tolerance or desensitization might account for the observations. NM-delta 8-THC, but not CY-delta 8-THC, attenuated the discriminative stimulus effects of CP 55,940 in rats several days following injection. Hence, addition of a nitrogen-containing functional group to a traditional cannabinoid structure does not eliminate agonist effects and may produce delayed attenuation of cannabinoid-induced pharmacological effects. PMID:9076759

  17. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

    Science.gov (United States)

    Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane; Amalric, Marianne; Kerkerian-Le Goff, Lydia

    2015-01-01

    Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease. PMID:26571268

  18. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson’s Disease

    Science.gov (United States)

    Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane

    2015-01-01

    Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson’s disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease. PMID:26571268

  19. 高血糖对6-OHDA诱导的PD模型大鼠行为学的影响%The Effect of Hyperglycemia on the Ethology of 6-OHDA Induced PD Rat Model

    Institute of Scientific and Technical Information of China (English)

    买尔哈巴; 孙景兰; 杨新玲; 贾玉敏; 耿飞飞

    2015-01-01

    Objective On the base of diabetic SD rat model, establish the Parkinson's disease(PD) rat model by two-spot u-nilaterally injection of 6-hydroxydopamine(6-OHDA) into the medial forebrain and evaluate this model in ethology. Meth-ods Ninety SD rats were randomly divided into five groups:normal group (n=5), physiological saline control group (n=10), diabetic group (n=20), PD group (n=20), and hyperglycemia-PD group (n=35). Establish diabetic rat model by high fat and high glucose diet and the intraperitoncal injection of streptozotocin. Establish PD hyperglycemia rat model by two-spot uni-laterally injection with 6-OHDA into the substanianigta parscompact(SNc) and ventral tegmental(VTA) stereotactically. And then ethology analysis (spontaneous behavioral lateralization, posture asymmetry, catalepsy test, revolving test) was conduct-ed at different time (the 7th, 14th, 21st and 28th day). Results There were significant differences in the parameters of spon-taneous behavioral lateralization, posture asymmetry, catalepsy test, revolving test between the PD group, hyperglycemia-PD group and normal group, physiological saline control group, diabetic group(P<0.01). There were significant differences in the parameters of spontaneous behavioral lateralization, catalepsy test between PD group and hyperglycemia-PD group. And the severity of spontaneous behavioral lateralization and rotating ring in PD group and hyperglycemia-PD group increased gradually with time. High blood sugar can not affect the re-volving test. Conclusion The ethological change of rats induced by injection of 6-OHDA increased with hyperglycemia and increased with time.%目的:在建立糖尿病SD大鼠模型的基础上,6-OHDA单侧毁损法建立高血糖-PD大鼠模型,探讨高血糖对PD大鼠行为学的影响。方法90只SD大鼠随机分为正常对照组(n=5),假手术组(n=10),糖尿病组(n=20),PD组(n=20)及高血糖-PD组(n=35)。采用高糖高脂饮食联合一次性腹腔注射链脲

  20. Pharmacological characterization of LY233053: A structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action

    International Nuclear Information System (INIS)

    This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 [cis-(+-)-4-[(2H-tetrazol-5-yl)methyl]piperidine-2-carboxylic acid], the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist. LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of [3H] CGS19755 (IC50 = 107 +/- 7 nM). No appreciable affinity in [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or [3H]kainate binding assays was observed (IC50 values greater than 10,000 nM). In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs. 40 microM NMDA). LY233053 was effective after in vivo systemic administration in a number of animal models. In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr). In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA. However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons. In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.). Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p. doses of LY233053. In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity

  1. Immunohistochemical evidence for the involvement of gonadotropin releasing hormone in neuroleptic and cataleptic effects of haloperidol in mice.

    Science.gov (United States)

    Fegade, Harshal A; Umathe, Sudhir N

    2016-04-01

    Blockade of dopamine D2 receptor by haloperidol is attributed for neuroleptic and cataleptic effects; and also for the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH agonist is reported to exhibit similar behavioural effects as that of haloperidol, and pre-treatment with GnRH antagonist is shown to attenuate the effects of haloperidol, suggesting a possibility that GnRH might mediate the effects of haloperidol. To substantiate such possibility, the influence of haloperidol on GnRH immunoreactivity (GnRH-ir) in the brain was studied in vehicle/antide pre-treated mice by peroxidase-antiperoxidase method. Initially, an earlier reported antide-haloperidol interaction in rat was confirmed in mice, wherein haloperidol (250μg/kg, i.p.) exhibited suppression of conditioned avoidance response (CAR) on two-way shuttle box, and induced catalepsy in bar test; and pre-treatment with antide (50μg/kg, s.c., GnRH antagonist) attenuated both effects of haloperidol. Immunohistochemical study was carried out to identify GnRH-ir in the brain, isolated 1h after haloperidol treatment to mice pre-treated with vehicle/antide. The morphometric analysis of microphotographs of brain sections revealed that haloperidol treatment increased integrated density units of GnRH-ir in various regions of the limbic system. Considering basal GnRH-ir in vehicle treated group as 100%, the increase in GnRH-ir after haloperidol treatment was by 100.98% in the medial septum; 54.26% in the bed nucleus of the stria terminalis; 1152.85% in the anteroventral periventricular nucleus; 120.79% in the preoptic area-organum vasculosum of the lamina terminalis and 138.82% in the arcuate nucleus. Antide did not influence basal and haloperidol induced increase in GnRH-ir in any of the regions. As significant increase in GnRH-ir after haloperidol treatment was observed in such regions of the brain which are reported to directly or indirectly communicate with the hippocampus and basal

  2. The effect of Ginkgo biloba extract on parkinsonisminduced biochemical changes in brain of irradiated rats

    International Nuclear Information System (INIS)

    Parkinson's disease (PD) is the second most common neuro degenerative disorder after Alzheimer's disease. In the present study, neuro modulatory effects of standardized ginkgo biloba extract (EGb 761) and low dose whole-body γ-irradiation in a reserpine model of rat Parkinsonism were investigated. Male Wistar rats were pretreated orally with EGb 761 (100 mg/kg BW/day for 3 weeks) or low dose whole-body γ-irradiation (0.25 Gy once a week for 6 weeks) and their combination (EGb 761 was received during the last three weeks of the irradiation period) and then subjected to intraperitoneal injection of reserpine (5 mg/kg BW dissolved in 1% acetic acid) 24h after last dose of EGb761or radiation. All rats were sacrificed 24h after reserpine injection. Depletion of striatal dopamine (DA) level, increased oxidative stress indicated via depletion of glutathione (GSH), increased malondialdehyde (MDA) and iron levels; decrease of dopamine metabolites metabolizing enzymes; indicated by decrease of glutathione-S transferase (GST) and NADPH-quinone oxidoreductase (NQO) activities; mitochondrial dysfunction; indicated by decline of complex I activity and adenosine triphosphate (ATP) level and increased apoptosis; indicated by the decrease of mitochondrial B cell lymphoma-2 protein (Bcl-2) level and as shown by transmission electron microscope (TEM) were observed in brain of reserpine-induced PD model group, along with behavioral study indicated by increased catalepsy score. Moreover, the level of GSH was correlated with the levels of both DA (r = 0.78) and MDA (r = -0.93). The level of Bcl-2 was correlated with the complex I activity (r = 0.94) and ATP level (r = 0.98). Results revealed that either EGb 761 or irradiation and their combination ameliorated most of the biochemical and behavioral changes induced by reserpine possibly via replenishment of normal glutathione levels. This study revealed that EGb 761, which is a widely used herbal medicine and low dose of whole-body

  3. Ethanolic extracts of Alstonia Scholaris and Bacopa Monniera possess neuroleptic activity due to anti-dopaminergic effect

    Directory of Open Access Journals (Sweden)

    Rajiv Jash

    2014-01-01

    Full Text Available Background: An increased inclination has been observed for the use of herbal drugs in chronic and incurable diseases. Treatment of psychiatric diseases like schizophrenia is largely palliative and more importantly, a prominent adverse effect prevails with the majority of anti-psychotic drugs, which are the extrapyramidal motor disorders. Existing anti-psychotic drug therapy is not so promising, and their adverse effect is a matter of concern for continuing the therapy for long duration. Objective: This experimental study was done to evaluate the neuroleptic activity of the ethanolic extracts of two plants Alstonia Scholaris and Bacopa Monnieri with different anti-psychotic animal models with a view that these plant extracts shall have no or at least reduced adverse effect so that it can be used for long duration. Materials and Methods: Two doses of both the extracts (100 and 200 mg/kg and also standard drug haloperidol (0.2 mg/kg were administered to their respective groups once daily with 5 different animal models. After that, the concentration of the dopamine neurotransmitter was estimated in two different regions of the brain viz. frontal cortex and striatum. Results: The result of the study indicated a significant reduction of amphetamine-induced stereotype and conditioned avoidance response for both the extracts compared with the control group, but both did not have any significant effect in phencyclidine-induced locomotor activity and social interaction activity. However, both the extracts showed minor signs of catalepsy compared to the control group. The study also revealed that the neuroleptic effect was due to the reduction of the dopamine concentration in the frontal cortex region of the rat brain. The results largely pointed out the fact that both the extract may be having the property to alleviate the positive symptoms of schizophrenia by reducing the dopamine levels of dopaminergic neurons of the brain. Conclusion: The estimation of

  4. On antipsychotic effects of l-Scoulerine%左旋金黄紫堇碱抗精神分裂症作用研究

    Institute of Scientific and Technical Information of China (English)

    高赟赟; 米桂芸; 刘帅; 杨征

    2016-01-01

    Aim To study the antipsychotic effects of l-Scoulerine ( l-SLR) . Methods NMDAreceptorantag-onist MK-801 was used to induce the positive and neg-ative symptoms of schizophrenia and cognitive impair-ment in animal models. The effects of l-SLR were eval-uated on schizophrenia induced by MK-801 and on ex-trapyramidal system. Results l-SLR (10,15 mg · kg - 1 , ip) could suppress pre-pulse inhibition damage in rats induced by MK-801 (0. 3 mg·kg - 1 , ip); l-SLR(30 mg·kg - 1 , ip) could inhibit climbing behav-iors in mice induced by apomorphine, which suggested that l-SLR had significant inhibiting effects on the posi-tive symptoms of schizophrenia by MK-801 and apo-morphine. l-SLR could also induce social contact inhi-bition and cognitive impairment induced by MK-801 (0. 2 mg · kg - 1 , ip), which proposed that l-SLR could improve the negative symptoms and cognitive im-pairment by MK-801. Catalepsy in mice could be caused by the treatment dose of haloperidol (0. 8 mg· kg - 1 , ip), not by that of l-SLR(30 mg·kg - 1 , ip). Conclusion I-SLR has significant effects on the posi-tive and negative symptoms of schizophrenia and cogni-tive impairment and, the effect of l-SLR under effective dose on extrapyramidal system is obviously much less than that of haloperidol and l-SPD.%目的:研究左旋金黄紫堇碱(l-SLR)的抗精神分裂症作用。方法采用 NMDA 受体拮抗剂 MK-801在动物模型上诱发精神分裂症的阳性症状、阴性症状及认知损伤;评价了化合物 l-SLR 对 MK-801诱发的精神分裂症的作用;并评价了 l-SLR 对小鼠锥体外系功能的影响。结果 MK-801(0.3 mg·kg -1, ip)引起大鼠前脉冲抑制损伤,l-SLR(10、15 mg·kg -1, ip)能抑制 MK-801引起的大鼠前脉冲抑制损伤;l-SLR(30 mg·kg -1, ip)能抑制多巴胺受体激动剂阿扑吗啡(2 mg·kg -1, sc)引起小鼠的攀爬行为,说明 l-LSR 对 MK-801及阿扑吗啡诱发的精神分裂症阳性症状有抑制作用。 l-SLR(30 mg·kg -1

  5. Study on Anti-depression Effect of Tanshinone%丹参酮的抗抑郁作用研究

    Institute of Scientific and Technical Information of China (English)

    张忠东; 曹莉; 程灶火

    2012-01-01

    OBJECTIVE: To study anti-depression effect of tanshinone. METHODS: Intragastric administration of Tanshinone. Depression model was induced by injection of reserpine (2 mg·kg-1) via tail vein, and the number of heavy-lidded eyes and akine-sia were observed and rectal temperature was determined. Depression model was induced by intraperitoneal injection of tetrabena-zine (40 mg·kg-1), and the number of catalepsy was observed. Mice was injected with reserpine (2 mg·kg-1) via tail vein to conduct tail suspension test and forced swimming test. The time of tail suspension immobility and swimming immobility were observed. The convusion of rats was induced by intravenous injection of MAO inhibitor (tryamine hydrochloride) to observe average value of rat's action and duration of slapping ,and beat. RESULTS: Tanshinone 60,30,20 mg·kg-1 could improve heavy-lidded eyes and swimming immobility and rised rectal temperature in depression symptoms of mice induced by reserpine(P<0.05). Tanshinone 60,30 mg·kg-1 could improve heavy-lidded eyes and swimming immobility in depression symptoms of mice induced by tet-rabenazine(P<0.01,P<0.05). It also shortened the time of tail suspension immobility and swimming immobility in despair symptoms of mice(P<0.01). Tanshinone 42,21,14 mg·kg-1 could depressed actin point in convusions symptoms of rats induced by try-pamine hydrochloride. Tanshinone 42,21 mg·kg-1 could shortened pat duriation in convusions symptoms model rats.CONCLU-SION: Tanshinone have certain anti-depressant effect.%目的:研究丹参酮的抗抑郁作用.方法:丹参酮灌胃给药.通过尾静脉注射利血平(2 mg·kg-1)复制小鼠抑郁模型,观察眼帘下垂动物数、运动不能动物数,测肛温;腹腔注射丁苯那嗪(40 mg·kg-1)复制小鼠抑郁模型,观察眼帘下垂动物数和僵住动物数;尾静脉注射利血平(2 mg·kg-1)后进行悬尾、强迫游泳实验,复制小鼠获得性绝望模型,观察小鼠悬尾不动时间和游泳不