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Sample records for cocaine-induced behavioral sensitization

  1. Cocaine-induced neuroadaptations in the dorsal striatum: glutamate dynamics and behavioral sensitization.

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    Parikh, Vinay; Naughton, Sean X; Shi, Xiangdang; Kelley, Leslie K; Yegla, Brittney; Tallarida, Christopher S; Rawls, Scott M; Unterwald, Ellen M

    2014-09-01

    Recent evidence suggests that diminished ability to control cocaine seeking arises from perturbations in glutamate homeostasis in the nucleus accumbens. However, the neurochemical substrates underlying cocaine-induced neuroadaptations in the dorsal striatum and how these mechanisms link to behavioral plasticity is not clear. We employed glutamate-sensitive microelectrodes and amperometry to study the impact of repeated cocaine administration on glutamate dynamics in the dorsolateral striatum of awake freely-moving rats. Depolarization-evoked glutamate release was robustly increased in cocaine-pretreated rats challenged with cocaine. Moreover, the clearance of glutamate signals elicited either by terminal depolarization or blockade of non-neuronal glutamate transporters slowed down dramatically in cocaine-sensitized rats. Repeated cocaine exposure also reduced the neuronal tone of striatal glutamate. Ceftriaxone, a β-lactam antibiotic that activates the astrocytic glutamate transporter, attenuated the effects of repeated cocaine exposure on synaptic glutamate release and glutamate clearance kinetics. Finally, the antagonism of AMPA glutamate receptors in the dorsolateral striatum blocked the development of behavioral sensitization to repeated cocaine administration. Collectively, these data suggest that repeated cocaine exposure disrupts presynaptic glutamate transmission and transporter-mediated clearance mechanisms in the dorsal striatum. Moreover, such alterations produce an over activation of AMPA receptors in this brain region leading to the sensitized behavioral response to repeated cocaine.

  2. The relationship between cocaine-induced increases in NAC1 and behavioral sensitization.

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    Wang, P J; Stromberg, Michael; Replenski, Stephen; Snyder-Mackler, Alexander; Mackler, Scott A

    2003-04-01

    Repeated exposure to cocaine can cause long-term behavioral changes in mammals, including an augmented locomotor response known as behavioral sensitization. A major goal of research is the identification of molecules associated with these behaviors. NAC1, a member of the POZ/BTB transcription factor family, exhibited increased mRNA levels in the nucleus accumbens of the rat weeks after cocaine use. NAC1 exists as two isoforms, each demonstrating the ability to inhibit transcription, but to different extents. The present experiments examined the time course for both NAC1 isoforms after five consecutive days of systemic cocaine administration in male rats. Tissues were collected from several central nervous system regions and underwent Western blot analysis. There was significantly greater expression of the long isoform, lNAC1 (cocaine 1.341+/-0.641; saline 1+/-0.321; P=.044), and the short isoform, sNAC1 (cocaine 3.038+/-2.816; saline 1+/-0.720; P=.001), in the nucleus accumbens of cocaine-treated rats. The olfactory tubercle also showed a significant increase, but only in sNAC1 expression and at only one time period. No other significant differences were observed for either isoform of NAC1 in any other brain region. The expression of lNAC1 exhibited an inverse relationship with behavioral sensitization in rats 1-3 months following repeated cocaine injections predicting approximately 40% of the variance in the behavior variables (R(2)=.387; and P=.031 for distance and P=.025 for ambulatory count). These results indicate that NAC1 expression is increased for a period of several months after chronic cocaine exposure. Furthermore, these data suggest that NAC1 may function as an endogenous inhibitor of behavioral sensitization. NAC1 represents a target for future studies examining cocaine-induced behavioral changes.

  3. Optogenetics reveals a role for accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine-induced behavioral sensitization.

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    Song, Shelly Sooyun; Kang, Byeong Jun; Wen, Lei; Lee, Hyo Jin; Sim, Hye-Ri; Kim, Tae Hyong; Yoon, Sehyoun; Yoon, Bong-June; Augustine, George J; Baik, Ja-Hyun

    2014-01-01

    Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have been proposed to contribute to drug-mediated addictive behaviors. Here we have used an optogenetic approach to examine the role of NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs) in cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding channelrhodopsin-2 (ChR2) were delivered into the NAc of D2R-Cre transgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2R-MSNs form local inhibitory circuits, because photostimulation of D2R-MSN evoked inhibitory postsynaptic currents (IPSCs) in neighboring MSNs. Photostimulation of NAc D2R-MSN in vivo affected neither the initiation nor the expression of cocaine-induced behavioral sensitization. However, photostimulation during the drug withdrawal period attenuated expression of cocaine-induced behavioral sensitization. These results show that D2R-MSNs of NAc play a key role in withdrawal-induced plasticity and may contribute to relapse after cessation of drug abuse.

  4. Optogenetics reveals a role for accumbal medium spiny neurons expressingdopamine D2 receptors in cocaine-induced behavioral sensitization

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    Shelly Sooyun eSong

    2014-10-01

    Full Text Available Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc have beenproposed to contribute to drug-mediated addictive behaviors. Here we have used anoptogenetic approach to examine the role of NAc medium spiny neurons (MSNs expressingdopamine D2 receptors (D2R in cocaine-induced behavioral sensitization. Adeno-associatedviral vectors coding channelrhodopsin-2 (ChR2 were delivered into the NAc of D2R-Cretransgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2RMSNsform local inhibitory circuits, because photostimulation of D2R-MSN evokedinhibitory postsynaptic currents in neighboring MSNs. Photostimulation of NAc D2R-MSNin vivo affected neither the initiation nor the expression of cocaine-induced behavioralsensitization. However, photostimulation during the drug withdrawal period attenuatedexpression of cocaine-induced behavioral sensitization. These results show that D2R-MSNsof NAc play a key role in withdrawal-induced plasticity and may contribute to relapse aftercessation of drug abuse.

  5. Different effects of valproate on methamphetamine-and cocaine-induced behavioral sensitization in mice

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    Jun-XuLi; Jian-HuiLiang

    2004-01-01

    Multiple intermittent administration of psychostimulants induces a behavioral sensitization, which is characterized by the augmentation of locomotor activity and stereotyped behavior, even after their long-term withdrawal. This kind of behavioral effects is thought to serve as a useful animal model that mimics the behavioral responses in drug craving. Dopamine

  6. A silent synapse-based mechanism for cocaine-induced locomotor sensitization.

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    Brown, Travis E; Lee, Brian R; Mu, Ping; Ferguson, Deveroux; Dietz, David; Ohnishi, Yoshinori N; Lin, Ying; Suska, Anna; Ishikawa, Masago; Huang, Yanhua H; Shen, Haowei; Kalivas, Peter W; Sorg, Barbara A; Zukin, R Suzanne; Nestler, Eric J; Dong, Yan; Schlüter, Oliver M

    2011-06-01

    Locomotor sensitization is a common and robust behavioral alteration in rodents whereby following exposure to abused drugs such as cocaine, the animal becomes significantly more hyperactive in response to an acute drug challenge. Here, we further analyzed the role of cocaine-induced silent synapses in the nucleus accumbens (NAc) shell and their contribution to the development of locomotor sensitization. Using a combination of viral vector-mediated genetic manipulations, biochemistry, and electrophysiology in a locomotor sensitization paradigm with repeated, daily, noncontingent cocaine (15 mg/kg) injections, we show that dominant-negative cAMP-element binding protein (CREB) prevents cocaine-induced generation of silent synapses of young (30 d old) rats, whereas constitutively active CREB is sufficient to increase the number of NR2B-containing NMDA receptors (NMDARs) at synapses and to generate silent synapses. We further show that occupancy of CREB at the NR2B promoter increases and is causally related to the increase in synaptic NR2B levels. Blockade of NR2B-containing NMDARs by administration of the NR2B-selective antagonist Ro256981 directly into the NAc, under conditions that inhibit cocaine-induced silent synapses, prevents the development of cocaine-elicited locomotor sensitization. Our data are consistent with a cellular cascade whereby cocaine-induced activation of CREB promotes CREB-dependent transcription of NR2B and synaptic incorporation of NR2B-containing NMDARs, which generates new silent synapses within the NAc. We propose that cocaine-induced activation of CREB and generation of new silent synapses may serve as key cellular events mediating cocaine-induced locomotor sensitization. These findings provide a novel cellular mechanism that may contribute to cocaine-induced behavioral alterations.

  7. Cocaine-induced behavioral sensitization decreases the expression of endocannabinoid signaling-related proteins in the mouse hippocampus.

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    Blanco, Eduardo; Galeano, Pablo; Palomino, Ana; Pavón, Francisco J; Rivera, Patricia; Serrano, Antonia; Alen, Francisco; Rubio, Leticia; Vargas, Antonio; Castilla-Ortega, Estela; Decara, Juan; Bilbao, Ainhoa; de Fonseca, Fernando Rodríguez; Suárez, Juan

    2016-03-01

    In the reward mesocorticolimbic circuits, the glutamatergic and endocannabinoid systems are implicated in neurobiological mechanisms underlying cocaine addiction. However, the involvement of both systems in the hippocampus, a critical region to process relational information relevant for encoding drug-associated memories, in cocaine-related behaviors remains unknown. In the present work, we studied whether the hippocampal gene/protein expression of relevant glutamate signaling components, including glutamate-synthesizing enzymes and metabotropic and ionotropic receptors, and the hippocampal gene/protein expression of cannabinoid type 1 (CB1) receptor and endocannabinoid metabolic enzymes were altered following acute and/or repeated cocaine administration resulting in conditioned locomotion and locomotor sensitization. Results showed that acute cocaine administration induced an overall down-regulation of glutamate-related gene expression and, specifically, a low phosphorylation level of GluA1. In contrast, locomotor sensitization to cocaine produced an up-regulation of several glutamate receptor-related genes and, specifically, an increased protein expression of the GluN1 receptor subunit. Regarding the endocannabinoid system, acute and repeated cocaine administration were associated with an increased gene/protein expression of CB1 receptors and a decreased gene/protein expression of the endocannabinoid-synthesis enzymes N-acyl phosphatidylethanolamine D (NAPE-PLD) and diacylglycerol lipase alpha (DAGLα). These changes resulted in an overall decrease in endocannabinoid synthesis/degradation ratios, especially NAPE-PLD/fatty acid amide hydrolase and DAGLα/monoacylglycerol lipase, suggesting a reduced endocannabinoid production associated with a compensatory up-regulation of CB1 receptor. Overall, these findings suggest that repeated cocaine administration resulting in locomotor sensitization induces a down-regulation of the endocannabinoid signaling that could

  8. Cocaine-induced hyperactivity and sensitization are dependent on GSK3.

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    Miller, Jonathan S; Tallarida, Ronald J; Unterwald, Ellen M

    2009-06-01

    Glycogen synthase kinase 3 (GSK3) is a critical mediator of many intracellular signaling systems. The activity of GSK3 is regulated by several kinases, with inactivation occurring via phosphorylation of the inhibitory serine-21 (alpha-isoform) and serine-9 (beta-isoform) residues. Here, we investigated whether acute cocaine administration regulates GSK3 activity and if inhibition of GSK3 by valproate or the selective GSK3 inhibitor SB 216763 would attenuate cocaine-induced behaviors in mice. Mice injected with cocaine (20 mg/kg, i.p.) showed a reduction in the phosphorylation of GSK3beta in the caudate putamen, reflecting an increase in the activity of the kinase. To assess the role of GSK3 in cocaine-induced hyperactivity, mice were pretreated with valproate (50-300 mg/kg, i.p.), SB 216763 (0.25-7.5 mg/kg, i.p.), or the appropriate vehicle prior to saline or cocaine (20 mg/kg, i.p.). Valproate or SB 216763 produced significant dose-dependent reductions in cocaine-induced ambulatory and stereotypic activity. Repeated administration of cocaine can result in an augmentation of the locomotor-stimulatory effects of the drug, a phenomenon referred to as sensitization. Mice pretreated with SB 216763 (2.5 mg/kg, i.p.) prior to daily cocaine (20 mg/kg, i.p.) for 5 days showed a significant attenuation of the development of cocaine-induced behavioral sensitization following a cocaine challenge on day 13. These results indicate that cocaine activated GSK3beta in the caudate putamen and that pharmacological inhibition of GSK3 reduced both the acute behavioral responses to cocaine and the long-term neuroadaptations produced by repeated cocaine, therefore suggesting a role for GSK3 in the behavioral and neurochemical manifestations associated with cocaine exposure.

  9. Cocaine-induced sensitization correlates with testosterone in male Japanese quail but not with estradiol in female Japanese quail.

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    Gill, Karin E; Madison, Farrah N; Akins, Chana K

    2015-01-01

    Research has indicated that gonadal hormones may mediate behavioral and biological responses to cocaine. Estrogen, in particular, has been shown to increase behavioral responding to cocaine in female rats relative to male rats. The current study investigated the effect of cocaine on locomotor activity and hormonal correlates in male and female Japanese quail (Coturnix japonica). In Japanese quail, circulating hormone levels can be manipulated without surgical alterations via modifying the photoperiod. Male and female quail were housed on either 8L:16D (light:dark) or 16L:8D (light:dark) cycle for 21days. Blood samples were taken prior to the beginning of the experiment and assays were performed to determine the levels of testosterone (T) and estradiol (E2). Quail were given injections of saline or cocaine (10 or 20mg/kg) once a day for 10days. Immediately after each injection, birds were placed in open field arenas and distance traveled was measured for 30min. Results showed that male quail housed under long-light conditions exhibited cocaine-induced sensitization to 10mg/kg cocaine which was correlated with the high levels of plasma T. Female quail housed under short-light conditions demonstrated sensitization to 10mg/kg cocaine, but this was not correlated with the levels of plasma E2. The current findings suggest that cocaine-induced locomotor activity was associated with T in males but not with E2 in females.

  10. CREB activity in dopamine D1 receptor expressing neurons regulates cocaine-induced behavioral effects

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    Ainhoa eBilbao

    2014-06-01

    Full Text Available IIt is suggested that striatal cAMP responsive element binding protein (CREB regulates sensitivity to psychostimulants. To test the cell-specificity of this hypothesis we examined the effects of a dominant-negative CREB protein variant expressed in dopamine receptor D1 (D1R neurons on cocaine-induced behaviors. A transgenic mouse strain was generated by pronuclear injection of a BAC-derived transgene harboring the A-CREB sequence under the control of the D1R gene promoter. Compared to wild-type, drug-naïve mutants showed moderate alterations in gene expression, especially a reduction in basal levels of activity-regulated transcripts such as Arc and Egr2. Drug-naïve mutants showed moderate alterations in gene expression, most prominently a reduction in basal levels of activity-regulated transcripts such as Arc and Egr2, when compared to wild-type controls. The behavioral responses to cocaine were elevated in mutant mice. Locomotor activity after acute treatment, psychomotor sensitization after intermittent drug injections and the conditioned locomotion after saline treatment were increased compared to wild-type littermates. Transgenic mice had significantly higher cocaine conditioned place preference, displayed normal extinction of the conditioned preference, but showed an augmented cocaine-seeking response following priming-induced reinstatement. This enhanced cocaine-seeking response was associated with increased levels of activity-regulated transcripts and prodynorphin. The primary reinforcing effects of cocaine were not altered in the mutant mice as they did not differ from wild-type in cocaine self-administration under a fixed ratio schedule at the training dose. Collectively, our data indicate that expression of a dominant-negative CREB variant exclusively in neurons expressing D1R is sufficient to recapitulate the previously reported behavioral phenotypes associated with virally expressed dominant-negative CREB.

  11. Availability of N-Methyl-d-Aspartate Receptor Coagonists Affects Cocaine-Induced Conditioned Place Preference and Locomotor Sensitization: Implications for Comorbid Schizophrenia and Substance Abuse.

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    Puhl, Matthew D; Berg, Alexandra R; Bechtholt, Anita J; Coyle, Joseph T

    2015-06-01

    Schizophrenia is associated with high prevalence of substance abuse. Recent research suggests that dysregulation of N-methyl-d-aspartate receptor (NMDAR) function may play a role in the pathophysiology of both schizophrenia and drug addiction, and thus, may account for this high comorbidity. Our laboratory has developed two transgenic mouse lines that exhibit contrasting NMDAR activity based on the availability of the glycine modulatory site (GMS) agonists d-serine and glycine. Glycine transporter 1 knockdowns (GlyT1(+/-)) exhibit NMDAR hyperfunction, whereas serine racemase knockouts (SR(-/-)) exhibit NMDAR hypofunction. We characterized the behavior of these lines in a cocaine-induced (20 mg/kg) conditioned place preference (CPP) and locomotor sensitization paradigm. Compared with wild-type mice, GlyT1(+/-) mice displayed hastened extinction of CPP and robust cocaine-induced reinstatement. SR(-/-) mice appeared to immediately "forget" the learned preference, because they did not exhibit cocaine-induced reinstatement and also displayed attenuated locomotor sensitization. Treatment of GlyT1(+/-) mice with gavestinel (10 mg/kg on day 1; 5 mg/kg on days 2-17), a GMS antagonist, attenuated cocaine-induced CPP and caused them to immediately "forget" the learned preference. Treatment of SR(-/-) mice with d-serine (300 mg/kg on day 1; 150 mg/kg on days 2-17) to normalize brain levels caused them to avoid the cocaine-paired side of the chamber during extinction. These results highlight NMDAR dysfunction as a possible neural mechanism underlying comorbid schizophrenia and substance abuse. Also, these findings suggest drugs that directly or indirectly activate the NMDAR GMS could be an effective treatment of cocaine abuse.

  12. Increased sensitivity to cocaine-induced analgesia in Spontaneously Hypertensive Rats (SHR).

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    Pamplona, Fabrício A; Vendruscolo, Leandro F; Takahashi, Reinaldo N

    2007-02-13

    This study examined the analgesic effect of cocaine in Spontaneously Hypertensive Rats (SHR), which are considered a suitable model for the study of attention deficit hyperactivity disorder (ADHD), and in Wistar (WIS) rats of both sexes using the hot-plate test. In addition, we tested whether habituation to the unheated hot-plate apparatus, that "normalizes" the basal hypoalgesic phenotype of SHR, alters the subsequent cocaine-induced analgesia (CIA) in this strain. SHR of both sexes were hypoalgesic compared to WIS rats in the hot-plate test and showed higher sensitivity to CIA. Habituation to the unheated hot-plate reduced the basal nociceptive latency of SHR, suggesting cognitive/emotional modulation of pain in this strain, but did not alter the magnitude of CIA. The present study shows increased sensitivity to CIA in SHR, which may be related to abnormalities in the mesocorticolimbic dopaminergic system. Further studies using SHR strain may reveal new information on the neurobiological mechanisms underlying ADHD and its co-morbidity with drug addiction.

  13. Microinjection of CART (cocaine- and amphetamine-regulated transcript) peptide into the nucleus accumbens inhibits the cocaine-induced upregulation of dopamine receptors and locomotor sensitization.

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    Peng, Qinghua; Sun, Xi; Liu, Ziyong; Yang, Jianghua; Oh, Ki-Wan; Hu, Zhenzhen

    2014-09-01

    Repeated exposure to addictive drugs enhances dopamine receptor (DR) signaling and the ultimate phosphorylation of the cyclic adenosine 5'-monophosphate (cAMP)-response element-binding protein (CREB)-regulated cocaine- and amphetamine-regulated transcript (CART) expression in the nucleus accumbens (NAcc). These effects are known to contribute to the expression of behavioral sensitization. CART peptides are neuropeptides that modulate drug reward and reinforcement. The present experiments investigated the effects of CART 55-102 microinjection into the NAcc on (1) the phosphorylation of CREB, (2) cAMP/protein kinase A (PKA) signaling and (3) extracellular signal-regulated kinase (ERK) phosphorylated kinase signaling. Here, we show that repeated microinjections into the NAcc of CART 55-102 peptides (1.0 or 2.5μg, 0.5μl/side) attenuates cocaine-induced enhancements of D1R, D2R and D3R phosphorylation in this sites. Furthermore, the microinjection of CART 55-102 followed by repeated injections of cocaine (15mg/kg) dose-dependently blocked the enhancement of cAMP levels, PKA activity and pERK and pCREB levels on the fifth day of cocaine administration. The cocaine-induced locomotor activity and behavioral sensitization in rats were also inhibited by the 5-day-microinjection of CART peptides. These results suggest that the phosphorylation of CREB by cocaine in the NAcc was blocked by the CART 55-102 peptide via the inhibition of D1R and D2R stimulation, D3R phosphorylation, cAMP/PKA signaling and ERK phosphorylated kinase signaling. These effects may have played a compensatory inhibitory role in the behavioral sensitization of rats that received microinjections of CART 55-102.

  14. Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats.

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    Vollbrecht, Peter J; Nobile, Cameron W; Chadderdon, Aaron M; Jutkiewicz, Emily M; Ferrario, Carrie R

    2015-12-01

    Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel "junk-food" diet on the development of obesity and metabolic dysfunction, 2) over-consumption of "junk-food" in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, "junk-food" diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals.

  15. Effects of paternal deprivation on cocaine-induced behavioral response and hypothalamic oxytocin immunoreactivity and serum oxytocin level in female mandarin voles.

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    Wang, Jianli; Fang, Qianqian; Yang, Chenxi

    2017-09-15

    Early paternal behavior plays a critical role in behavioral development in monogamous species. The vast majority of laboratory studies investigating the influence of parental behavior on cocaine vulnerability focus on the effects of early maternal separation. However, comparable studies on whether early paternal deprivation influences cocaine-induced behavioral response are substantially lacking. Mandarin vole (Microtus mandarinus) is a monogamous rodent with high levels of paternal care. After mandarin vole pups were subjected to early paternal deprivation, acute cocaine- induced locomotion, anxiety- like behavior and social behavior were examined in 45day old female pups, while hypothalamic oxytocin immunoreactivity and serum oxytocin level were also assessed. We found that cocaine increased locomotion and decreased social investigation, contact behavior and serum oxytocin level regardless of paternal care. Cocaine increased anxiety levels and decreased oxytocin immunoreactive neurons of the paraventricular nuclei and supraoptic nuclei in the bi-parental care group, whilst there were no specific effects in the paternal deprivation group. These results indicate that paternal deprivation results in different behavioral response to acute cocaine exposure in adolescents, which may be in part associated with the alterations in oxytocin immunoreactivity and peripheral OT level. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Impaired behavioral sensitization to cocaine in vasopressin deficient rats.

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    Post, R M; Contel, N R; Gold, P

    1982-12-13

    Behavioral sensitization to cocaine involves progressive and long-lasting increases in hyperactivity and stereotypy in response to the same daily dose. In order to test whether vasopressin, a neuro-hormone implicated in drug tolerance and in other models of learning and memory, affected behavioral sensitization, cocaine was administered daily to animals with hereditary absence of vasopressin. Brattleboro homozygotes which lack vasopressin show deficient onset and persistence of cocaine-induced behavioral sensitization compared to heterozygote, litter-mate controls. These data extend previous reports of vasopressin's role in memory and long-term coding of behavior to the model of pharmacologically-induced behavioral sensitization.

  17. Activation of mGluR7s inhibits cocaine-induced reinstatement of drug-seeking behavior by a nucleus accumbens glutamate-mGluR2/3 mechanism in rats.

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    Li, Xia; Li, Jie; Gardner, Eliot L; Xi, Zheng-Xiong

    2010-09-01

    The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown. Using a rat relapse model, we found that systemic administration of AMN082, a selective mGluR7 allosteric agonist, dose-dependently inhibits cocaine-induced reinstatement of drug-seeking behavior. Intracranial microinjections of AMN082 into the nucleus accumbens (NAc) or ventral pallidum, but not the dorsal striatum, also inhibited cocaine-primed reinstatement, an effect that was blocked by local co-administration of MMPIP, a selective mGluR7 antagonist. In vivo microdialysis demonstrated that cocaine priming significantly increased extracellular dopamine in the NAc, ventral pallidum and dorsal striatum, while increasing extracellular glutamate in the NAc only. AMN082 alone failed to alter extracellular dopamine, but produced a slow-onset long-lasting increase in extracellular glutamate in the NAc only. Pre-treatment with AMN082 dose-dependently blocked both cocaine-enhanced NAc glutamate and cocaine-induced reinstatement, an effect that was blocked by MMPIP or LY341497 (a selective mGluR2/3 antagonist). These data suggest that mGluR7 activation inhibits cocaine-induced reinstatement of drug-seeking behavior by a glutamate-mGluR2/3 mechanism in the NAc. The present findings support the potential use of mGluR7 agonists for the treatment of cocaine addiction.

  18. Cocaine-induced locomotor activity is increased by prior handling in adolescent but not adult female rats

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    Maldonado, Antoniette M.; Kirstein, Cheryl L.

    2017-01-01

    Adolescence is a period of transition that is associated with increased levels of stress and a heightened propensity to initiate drug use. Neuronal development is still occurring during this transitional period, which includes the continued development of the dopamine system during the adolescent period. In the present study, the effects of pre-test handling on cocaine-induced locomotor activity were investigated among female adolescent and young adult rats upon presentation to a novel environment. On postnatal days (PND) 41–44 and 56–59 animals were handled (b.i.d.) in the colony room for 3 min. On PND 45 or PND 60, animals were removed from the colony room, weighed, and administered an acute injection of either cocaine or saline and presented to a novel environment where behavior was recorded for 30 min. Adolescent females (PND 45) that were handled prior to cocaine administration demonstrated elevated levels of cocaine-induced activity relative to their age-matched non-handled counterparts and also to their handled-adult counterparts. In contrast, among non-handled animals, young adults (PND 60) exhibited elevated drug-induced locomotion at several time points during the trial. Non-handled adolescent animals demonstrated the previously described “hyporesponsive” behavioral profile relative to their non-handled adult counterparts. The results from the present experiment indicate that adolescent animals may be more sensitive to basic laboratory manipulations such as pre-test handling, and care must be taken when utilizing adolescent animals in behavioral testing. Handling appears to be a sensitive manipulation in elucidating differences in cocaine-induced behavioral activation between ages. PMID:16176824

  19. Cocaine-induced pulmonary changes: HRCT findings

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    Renata Rocha de Almeida

    2015-08-01

    Full Text Available AbstractObjective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease.Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors.Results:In 8 patients (36.4%, the clinical and tomographic findings were consistent with "crack lung", those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%, barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each.Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings.

  20. Cocaine-induced pulmonary changes: HRCT findings *

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    de Almeida, Renata Rocha; Zanetti, Gláucia; Souza, Arthur Soares; de Souza, Luciana Soares; Silva, Jorge Luiz Pereira e; Escuissato, Dante Luiz; Irion, Klaus Loureiro; Mançano, Alexandre Dias; Nobre, Luiz Felipe; Hochhegger, Bruno; Marchiori, Edson

    2015-01-01

    Abstract Objective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease. Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors. Results: In 8 patients (36.4%), the clinical and tomographic findings were consistent with "crack lung", those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%), barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each. Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings. PMID:26398752

  1. Cocaine-induced pulmonary changes: HRCT findings

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    Almeida, Renata Rocha de; Zanetti, Glaucia; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Programa de Pos-Graduacao em Radiologia; Souza Junior, Arthur Soares [Faculdade de Medicina de Petropolis, Petropolis, RJ (Brazil); Souza, Luciana Soares de [Ultra-X, Sao Jose do Rio Preto, SP (Brazil); Silva, Jorge Luiz Pereira e [Universidade Federal da Bahia (UFBA), Salvador (Brazil). Dep. de Medicina e Apoio Diagnostico; Escuissato, Dante Luiz [Universidade Federal do Parana (UFPR), Curitiba (Brazil). Dept. de Clinica Medica; Irion, Klaus Loureiro [Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool (United Kingdom); Mancano, Alexandre Dias [Hospital Anchieta, Taguatinga, DF (Brazil); Nobre, Luiz Felipe [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil); Hochhegger, Bruno [Universidade Federal de Ciencias da Saude de Porto Alegre, Porto Alegre, RS (Brazil); Marchiori, Edson [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil)

    2015-07-15

    Objective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease. Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors. Results: In 8 patients (36.4%), the clinical and tomographic findings were consistent with 'crack lung', those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%), barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each. Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings. (author)

  2. Dopamine transporter inhibition is required for cocaine-induced stereotypy

    OpenAIRE

    Tilley, Michael R.; Gu, Howard H.

    2008-01-01

    The primary mechanism by which cocaine induces stereotypy has been difficult to discern because cocaine has three high affinity targets, the reuptake transporters for dopamine (DAT), norepinephrine, and serotonin. To dissect out the role of DAT in cocaine effects, we generated a knock-in mouse line with a cocaine insensitive DAT (DAT-CI mice). DAT-CI mice provide a powerful tool that can directly test whether DAT inhibition is important for cocaine-induced stereotypy. We found that acute coca...

  3. Glycogen synthase kinase-3β in the ventral tegmental area mediates diurnal variations in cocaine-induced conditioned place preference in rats.

    Science.gov (United States)

    Li, Su-Xia; Wei, Yi-Ming; Shi, Hai-Shui; Luo, Yi-Xiao; Ding, Zeng-Bo; Xue, Yan-Xue; Lu, Lin; Yu, Chang-Xi

    2014-11-01

    Cocaine sensitization and reward are reported to be under the influence of diurnal rhythm. However, no previous studies have reported brain areas that play a role as modulators and underlie the mechanism of diurnal variations in cocaine reward. We examined (1) the diurnal rhythm of glycogen synthase kinase-3β (GSK-3β) activity in the suprachiasmatic nucleus (SCN) and reward-related brain areas in naive rats; (2) the effect of day and night on the acquisition of cocaine-induced conditioned place preference (CPP); (3) the influence of cocaine-induced CPP on GSK-3β activity in the SCN and reward-related brain areas; and (4) the effect of the GSK-3β inhibitor SB216763 microinjected bilaterally into the ventral tegmental area (VTA) on cocaine-induced CPP. A significant diurnal rhythm of GSK-3β activity was found in the SCN and reward-related brain areas, with diurnal variations in cocaine-induced CPP. GSK-3β activity in the SCN and reward-related brain areas exhibited marked diurnal variations in rats treated with saline. GSK-3β activity in rats treated with cocaine exhibited distinct diurnal variations only in the prefrontal cortex and VTA. Cocaine decreased the expression of phosphorylated GSK-3β (i.e. increased GSK-3β activity) only in the VTA in rats trained and tested at ZT4 and ZT16. SB216763 microinjected into the VTA bilaterally eliminated the diurnal variations in cocaine-induced CPP, but did not affect the acquisition of cocaine-induced CPP. These findings suggest that the VTA may be a critical area involved in the diurnal variations in cocaine-induced CPP, and GSK-3β may be a regulator of diurnal variations in cocaine-induced CPP.

  4. Sonographic and Endoscopic Findings in Cocaine-Induced Ischemic Colitis

    DEFF Research Database (Denmark)

    Leth, Thomas; Wilkens, Rune; Bonderup, Ole Kristian

    2015-01-01

    Cocaine-induced ischemic colitis is a recognized entity. The diagnosis is based on clinical and endoscopic findings. However, diagnostic imaging is helpful in the evaluation of abdominal symptoms and prior studies have suggested specific sonographic findings in ischemic colitis. We report...

  5. Neuropeptide Y Y5 receptor antagonism causes faster extinction and attenuates reinstatement in cocaine-induced place preference

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Wörtwein, Gitta; Fink-Jensen, Anders

    2013-01-01

    . In the present study, we further explored potential anti-addiction-related effects of Y5 antagonism in another murine model of cocaine addiction-related behavior: conditioned place-preference (CPP). Using this model, it was tested whether blockade or deficiency of the NPY Y5 receptor could influence...... the induction, extinction or reinstatement of a conditioned cocaine response. We found that the Y5 antagonist L-152,804 causes faster extinction and reduced reinstatement of cocaine-induced CPP but did not reduce the ability of cocaine to induce CPP. Similarly, Y5-KO mice displayed faster extinction......, and reinstatement of cocaine-induced CPP was absent. The development of CPP for cocaine was similar between Y5-KO and WT mice. Taken together, the present data show that Y5 antagonism attenuates relapse to cocaine addiction-related behavior. Prevention of relapse is considered to be of pivotal importance...

  6. Handling alters cocaine-induced activity in adolescent but not adult male rats

    Science.gov (United States)

    Maldonado, Antoniette M.; Kirstein, Cheryl L.

    2017-01-01

    The developmental period of adolescence is one that is characterized by increased levels of stress and vulnerability to drugs. Pre-test handling is an experimental manipulation that is used to acclimate animals prior to behavioral testing and exposure to a novel environment. Therefore, the present study was conducted in order to address the issue of pre-test handling of adolescent and adult male rats on subsequent cocaine-induced locomotor activity upon presentation to a novel environment. On days one through four, postnatal day (PND) 41–44 or PND 56–59, respectively, animals were handled b.i.d. for three minutes. On the fifth day, PND 45 or PND 60, animals were administered 30 mg/kg/ip cocaine or saline and immediately placed in a novel environment where locomotor activity was measured for 30 minutes. Cocaine increased locomotor activity similarly in all non-handled animals, regardless of age. Interestingly, adolescent animals expressed a differential effect when handled prior to an acute cocaine administration. Specifically, handling increased cocaine-induced locomotor activity in adolescent but not adult animals. These findings indicate that adolescent males that have been acclimated to the handling procedure experience significantly more behavioral reactivity than do adults to a high dose of cocaine upon exposure to a novel environment. PMID:15708784

  7. Cocaine-Induced Reinstatement of a Conditioned Place Preference in Developing Rats: Involvement of the D2 Receptor

    Directory of Open Access Journals (Sweden)

    Kimberly A. Badanich

    2012-10-01

    Full Text Available Reinstatement of conditioned place preferences have been used to investigate physiological mechanisms mediating drug-seeking behavior in adolescent and adult rodents; however, it is still unclear how psychostimulant exposure during adolescence affects neuron communication and whether these changes would elicit enhanced drug-seeking behavior later in adulthood. The present study determined whether the effects of intra-ventral tegmental area (VTA or intra-nucleus accumbens septi (NAcc dopamine (DA D2 receptor antagonist infusions would block (or potentiate cocaine-induced reinstatement of conditioned place preferences. Adolescent rats (postnatal day (PND 28–39 were trained to express a cocaine place preference. The involvement of D2 receptors on cocaine-induced reinstatement was determined by intra-VTA or intra-NAcc infusion of the DA D2 receptor antagonist sulpiride (100 μM during a cocaine-primed reinstatement test (10 mg/kg cocaine, i.p.. Infusion of sulpiride into the VTA but not the NAcc blocked reinstatement of conditioned place preference. These data suggest intrinsic compensatory mechanisms in the mesolimbic DA pathway mediate responsivity to cocaine-induced reinstatement of a conditioned place preference during development.

  8. Neuroticism associated with cocaine-induced psychosis in cocaine-dependent patients: a cross-sectional observational study.

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    Carlos Roncero

    Full Text Available BACKGROUND: Cocaine consumption can induce transient psychotic symptoms, which has been correlated with more severe addiction and aggressive behavior. However, little is known about the nature of the relationship between personality traits and psychotic symptoms in cocaine-dependent patients. This study examined the relationship between neuroticism and cocaine-induced psychosis. METHODS: A total of 231 cocaine-dependent patients seeking treatment were recruited to the study. Personality was evaluated by the Zuckerman-Kuhlman Personality Questionnaire. Cocaine-induced psychosis questionnaire, SCID-I, and SCID-II were used to evaluate comorbidity and clinical characteristics. Data analysis was performed in three steps: descriptive, bivariate, and multivariate analyses. RESULTS: Cocaine-induced psychosis was reported in 65.4% of the patients and some personality disorder in 46.8%. Two personality dimensions (Neuroticism-Anxiety and Aggression-Hostility presented a significant effect on the risk of experiencing psychotic symptoms (t(229 = 2.69, p = 0.008; t(229 = 2.06, p = 0.004, and patients with psychotic symptoms showed higher scores in both variables. On the multivariate analysis, only Neuroticism remained as a significant personality factor independently associated with psychotic symptoms (Wald = 7.44, p<0.05, OR = 1.08, CI 95% 1.02-1.16 after controlling for age, gender and number of consumption substances. CONCLUSIONS: An association between high neuroticism scores and presence of psychotic symptoms induced by cocaine has been found, independently of other consumption variables. Personality dimensions should be evaluated in cocaine-dependent patients in order to detect high scores of neuroticism and warn patients about the risk of developing cocaine-induced psychotic symptoms.

  9. Altered ratio of D1 and D2 dopamine receptors in mouse striatum is associated with behavioral sensitization to cocaine.

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    Dawn Thompson

    Full Text Available BACKGROUND: Drugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R availability in the brain. Such a decrease consequently alters the ratio of D1R:D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified. METHODS AND FINDINGS: ETHICS STATEMENT: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT and G protein coupled receptor associated sorting protein-1 (GASP-1 knock out (KO mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine. CONCLUSIONS: Together, our data suggests that changes in the ratio of the D1:D2R could contribute to cocaine-induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization.

  10. Cocaine-induced vasculitis: is this a new trend?

    Directory of Open Access Journals (Sweden)

    García Pérez MR

    2013-10-01

    Full Text Available Miraida Reneé García Pérez,1 Vanessa L Ortiz-González,1 Maria Betancourt,1 Rogelio Mercado21Department of Internal Medicine, San Juan City Hospital, 2Department of Dermatology, University of Puerto Rico School of Medicine, San Juan, Puerto RicoAbstract: Cocaine-induced vasculitis is a rare complication found in drug abusers. It occurs due to cocaine adulterated with levamisole. Levamisole was once used as a chemotherapy and immunomodulator for different conditions. One of the side effects of this medication is necrotizing vasculitis which has been reported in the US and Puerto Rico. Here we present another case of cocaine induced vasculitis in Puerto Rico. We describe a 43-year-old female with past medical history of bronchial asthma, migraine, and crack smoking who presented to the emergency room due to blood in her urine for 5 days. She also reported fever, chills, and fatigue. At the physical exam she had a right knee ulcer with swelling erythema, warmth, and pain. Also, she had retiform purpuric plaque lesions in her ears, bilaterally. Eroded plaques with elevated borders at left foot and finger dorsum were also present. Laboratory workup was positive for cocaine. The patient showed leucopenia and microcytic anemia with a normal absolute neutrophil count in her cell blood count. Blood cultures, urine cultures, and ulcer cultures were negative. Urinalysis was positive for proteinuria and hematuria. Also, the patient had positive perinuclear anti-neutrophil cytoplasmic antibody, cytoplasmic anti-neutrophil cytoplasmic antibody, and antinuclear antibody tests and elastase specificity. She showed negative anticardiolipin and lupus anticoagulant antibodies. Her complement levels were decreased. The punch biopsy of her ear showed superficial thrombosis of superficial vascular plexus with perivascular lymphocytic infiltrates and deeper sections showed epidermal necrosis and necrotizing vasculitis. She was started on a high dose of steroids, but

  11. Cocaine-induced psychotic disorders: presentation, mechanism, and management.

    Science.gov (United States)

    Tang, Yilang; Martin, Nancy L; Cotes, Robert O

    2014-01-01

    Cocaine, the third mostly commonly used illicit drug in the United States, has a wide range of neuropsychiatric effects, including transient psychotic symptoms. When psychotic symptoms occur within a month of cocaine intoxication or withdrawal, the diagnosis is cocaine-induced psychotic disorder (CIPD). Current evidence suggests those with CIPD are likely to be male, have longer severity and duration of cocaine use, use intravenous cocaine, and have a lower body mass index. Differentiating CIPD from a primary psychotic disorder requires a detailed history of psychotic symptoms in relation to substance use and often a longitudinal assessment. Treatment includes providing a safe environment, managing agitation and psychosis, and addressing the underlying substance use disorder. This review begins with a clinical case and summarizes the literature on CIPD, including clinical presentation, differential diagnosis, mechanism and predictors of illness, and treatment.

  12. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, M.F. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Couto-Pereira, N.S. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS, Brasil, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Nin, M.S. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Instituto Porto Alegre, Centro Metodista do Sul, Curso de Farmácia, Porto Alegre, RS, Brasil, Curso de Farmácia, Centro Metodista do Sul, Instituto Porto Alegre, Porto Alegre, RS (Brazil); Gomez, R. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia, Porto Alegre, RS, Brasil, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Barros, H.M.T. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

    2014-05-09

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  13. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Vilela, Luciano R. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Gobira, Pedro H.; Viana, Thercia G. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Medeiros, Daniel C.; Ferreira-Vieira, Talita H. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doria, Juliana G. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Rodrigues, Flávia [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Aguiar, Daniele C. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Pereira, Grace S.; Massessini, André R. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ribeiro, Fabíola M. [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Oliveira, Antonio Carlos P. de [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moraes, Marcio F.D., E-mail: mfdm@icb.ufmg.br [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moreira, Fabricio A., E-mail: fabriciomoreira@icb.ufmg.br [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2015-08-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB{sub 1} receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB{sub 1} receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis

  14. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity.

    Science.gov (United States)

    Vilela, Luciano R; Gobira, Pedro H; Viana, Thercia G; Medeiros, Daniel C; Ferreira-Vieira, Talita H; Doria, Juliana G; Rodrigues, Flávia; Aguiar, Daniele C; Pereira, Grace S; Massessini, André R; Ribeiro, Fabíola M; de Oliveira, Antonio Carlos P; Moraes, Marcio F D; Moreira, Fabricio A

    2015-08-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB1 receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB1 receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity.

  15. Cocaine-induced vasculitis: is this a new trend?

    Science.gov (United States)

    García Pérez, Miraida Reneé; Ortiz-González, Vanessa L; Betancourt, Maria; Mercado, Rogelio

    2013-01-01

    Cocaine-induced vasculitis is a rare complication found in drug abusers. It occurs due to cocaine adulterated with levamisole. Levamisole was once used as a chemotherapy and immunomodulator for different conditions. One of the side effects of this medication is necrotizing vasculitis which has been reported in the US and Puerto Rico. Here we present another case of cocaine induced vasculitis in Puerto Rico. We describe a 43-year-old female with past medical history of bronchial asthma, migraine, and crack smoking who presented to the emergency room due to blood in her urine for 5 days. She also reported fever, chills, and fatigue. At the physical exam she had a right knee ulcer with swelling erythema, warmth, and pain. Also, she had retiform purpuric plaque lesions in her ears, bilaterally. Eroded plaques with elevated borders at left foot and finger dorsum were also present. Laboratory workup was positive for cocaine. The patient showed leucopenia and microcytic anemia with a normal absolute neutrophil count in her cell blood count. Blood cultures, urine cultures, and ulcer cultures were negative. Urinalysis was positive for proteinuria and hematuria. Also, the patient had positive perinuclear anti-neutrophil cytoplasmic antibody, cytoplasmic anti-neutrophil cytoplasmic antibody, and antinuclear antibody tests and elastase specificity. She showed negative anticardiolipin and lupus anticoagulant antibodies. Her complement levels were decreased. The punch biopsy of her ear showed superficial thrombosis of superficial vascular plexus with perivascular lymphocytic infiltrates and deeper sections showed epidermal necrosis and necrotizing vasculitis. She was started on a high dose of steroids, but could not complete the treatment because she escaped from the hospital before finishing her treatment.

  16. Extracellular signal-regulated kinase (ERK) signaling in the ventral tegmental area mediates cocaine-induced synaptic plasticity and rewarding effects

    OpenAIRE

    Pan, Bin; Zhong, Peng; Sun, Dalong; Liu, Qing-song

    2011-01-01

    Drugs of abuse such as cocaine induce long-term synaptic plasticity in the reward circuitry, which underlies the formation of drug-associated memories and addictive behavior. We reported previously that repeated cocaine exposure in vivo facilitates long-term potentiation in dopamine neurons of the ventral tegmental area (VTA) by reducing the strength of GABAergic inhibition and that endocannabinoid (eCB)-dependent long-term depression at inhibitory synapses (I-LTD) constitutes a mechanism for...

  17. Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

    Directory of Open Access Journals (Sweden)

    Meriem Gaval-Cruz

    Full Text Available The anti-alcoholism medication, disulfiram (Antabuse, decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH, the enzyme that converts dopamine (DA to norepinephrine (NE in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/- mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/- and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor enhance qualitatively different cocaine-induced behaviors.

  18. Oleoylethanolamide dose-dependently attenuates cocaine-induced behaviours through a PPARα receptor-independent mechanism.

    Science.gov (United States)

    Bilbao, Ainhoa; Blanco, Eduardo; Luque-Rojas, María Jesús; Suárez, Juan; Palomino, Ana; Vida, Margarita; Araos, Pedro; Bermúdez-Silva, Francisco J; Fernández-Espejo, Emilio; Spanagel, Rainer; Rodríguez de Fonseca, Fernando

    2013-01-01

    Oleoylethanolamide (OEA) is an acylethanolamide that acts as an agonist of nuclear peroxisome proliferator-activated receptor alpha (PPARα) to exert their biological functions, which include the regulation of appetite and metabolism. Increasing evidence also suggests that OEA may participate in the control of reward-related behaviours. However, direct experimental evidence for the role of the OEA-PPARα receptor interaction in drug-mediated behaviours, such as cocaine-induced behavioural phenotypes, is lacking. The present study explored the role of OEA and its receptor PPARα on the psychomotor and rewarding responsiveness to cocaine using behavioural tests indicative of core components of addiction. We found that acute administration of OEA (1, 5 or 20 mg/kg, i.p.) reduced spontaneous locomotor activity and attenuated psychomotor activation induced by cocaine (20 mg/kg) in C57Bl/6 mice. However, PPARα receptor knockout mice showed normal sensitization, although OEA was capable of reducing behavioural sensitization with fewer efficacies. Furthermore, conditioned place preference and reinstatement to cocaine were intact in these mice. Our results indicate that PPARα receptor does not play a critical, if any, role in mediating short- and long-term psychomotor and rewarding responsiveness to cocaine. However, further research is needed for the identification of the targets of OEA for its inhibitory action on cocaine-mediated responses.

  19. Serotonin2C receptor stimulation inhibits cocaine-induced Fos expression and DARPP-32 phosphorylation in the rat striatum independently of dopamine outflow.

    Science.gov (United States)

    Devroye, Céline; Cathala, Adeline; Maitre, Marlène; Piazza, Pier Vincenzo; Abrous, Djoher Nora; Revest, Jean-Michel; Spampinato, Umberto

    2015-02-01

    The serotonin(2C) receptor (5-HT(2C)R) is known to control dopamine (DA) neuron function by modulating DA neuronal firing and DA exocytosis at terminals. Recent studies assessing the influence of 5-HT(2C)Rs on cocaine-induced neurochemical and behavioral responses have shown that 5-HT2CRs can also modulate mesoaccumbens DA pathway activity at post-synaptic level, by controlling DA transmission in the nucleus accumbens (NAc), independently of DA release itself. A similar mechanism has been proposed to occur at the level of the nigrostriatal DA system. Here, using in vivo microdialysis in freely moving rats and molecular approaches, we assessed this hypothesis by studying the influence of the 5-HT(2C)R agonist Ro 60-0175 on cocaine-induced responses in the striatum. The intraperitoneal (i.p.) administration of 1 mg/kg Ro 60-0175 had no effect on the increase in striatal DA outflow induced by cocaine (15 mg/kg, i.p.). Conversely, Ro 60-0175 inhibited cocaine-induced Fos immunoreactivity and phosphorylation of the DA and c-AMP regulated phosphoprotein of Mr 32 kDa (DARPP-32) at threonine 75 residue in the striatum. Finally, the suppressant effect of Ro 60-0175 on cocaine-induced DARPP-32 phosphorylation was reversed by the selective 5-HT(2C)R antagonist SB 242084 (0.5 mg/kg, i.p.). In keeping with the key role of DARPP-32 in DA neurotransmission, our results demonstrate that 5-HT(2C)Rs are capable of modulating nigrostriatal DA pathway activity at post-synaptic level, by specifically controlling DA signaling in the striatum.

  20. Removal of perineuronal nets in the medial prefrontal cortex impairs the acquisition and reconsolidation of a cocaine-induced conditioned place preference memory.

    Science.gov (United States)

    Slaker, Megan; Churchill, Lynn; Todd, Ryan P; Blacktop, Jordan M; Zuloaga, Damian G; Raber, Jacob; Darling, Rebecca A; Brown, Travis E; Sorg, Barbara A

    2015-03-11

    Pyramidal neurons in the medial prefrontal cortex (mPFC) critically contribute to cocaine-seeking behavior in humans and rodents. Activity of these neurons is significantly modulated by GABAergic, parvalbumin-containing, fast-spiking interneurons, the majority of which are enveloped by specialized structures of extracellular matrix called perineuronal nets (PNNs), which are integral to the maintenance of many types of plasticity. Using a conditioned place preference (CPP) procedure, we found that removal of PNNs primarily from the prelimbic region of the mPFC of adult, male, Sprague Dawley rats impaired the acquisition and reconsolidation of a cocaine-induced CPP memory. This impairment was accompanied by a decrease in the number of c-Fos-positive cells surrounded by PNNs. Following removal of PNNs, the frequency of inhibitory currents in mPFC pyramidal neurons was decreased; but following cocaine-induced CPP, both frequency and amplitude of inhibitory currents were decreased. Our findings suggest that cocaine-induced plasticity is impaired by removal of prelimbic mPFC PNNs and that PNNs may be a therapeutic target for disruption of cocaine CPP memories.

  1. Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL/6J mice.

    Science.gov (United States)

    Freet, Christopher S; Lawrence, Antoneal L

    2015-10-01

    Growing evidence implicates glutamate homeostasis in a number of behaviors observed in addiction such as acquisition of drug taking, motivation, and reinstatement. To date, however, the role of glutamate homeostasis in the avoidance of natural rewards due to exposure to drugs of abuse has received little attention. The aim of the current study was to evaluate the beta-lactam antibiotic, ceftriaxone, which has been shown to normalize disrupted glutamate homeostasis associated with exposure to drugs of abuse, in cocaine-induced suppression of saccharin intake in C57BL/6J mice. Briefly, C57BL/6J mice received daily injections of either 200mg/kg ceftriaxone or saline. Mice were then given access to 0.15% saccharin for 1h and immediately injected intraperitoneally with either saline or 30 mg/kg cocaine; taste-drug pairings occurred every 24h for 5 trials followed by a final CS only trial. One week following taste-drug pairings, extinction was evaluated in a series of one- and two-bottle saccharin intake tests. Individual differences in cocaine-induced suppression were observed (i.e., low and high suppressors) with differential effects of ceftriaxone. Ceftriaxone delayed suppression of saccharin intake in high suppressors but prevented suppression in low suppressors. In addition, ceftriaxone history facilitated extinction in the high suppressors. These data suggest that changes in glutamate homeostasis may be involved in the formation and expression of cocaine-induced suppression of saccharin intake in mice.

  2. Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain

    Science.gov (United States)

    You, Jiang; Volkow, Nora D.; Park, Kicheon; Zhang, Qiujia; Clare, Kevin; Du, Congwu

    2017-01-01

    Occurrence of transient ischemic attacks (TIA) and cerebral strokes is a recognized risk associated with cocaine abuse. Here, we use a rodent model along with optical imaging to study cocaine-induced TIA and the associated dynamic changes in cerebral blood flow velocity (CBFv) and cerebrovasculature. We show that chronic cocaine exposure in mice resulted in marked cortical hypoperfusion, in significant arterial and venous vasoconstriction, and in a sensitized vascular response to an acute cocaine injection. Starting after 10 days of exposure, an acute cocaine challenge to these mice resulted in a TIA, which presented as hemiparalysis and was associated with an abrupt exacerbation of CBFv. The severity of the TIA correlated with the decreases in cortical CBFv such that the greater the decreases in flow, the longer the TIA duration. The severity of TIA peaked around 17–22 days of cocaine exposure and decreased thereafter in parallel to a reorganization of CBFv from superficial to deep cortical layers, along with an increase in vessel density into these layers. Here, we document for the first time to our knowledge evidence of a TIA in an animal model of chronic cocaine exposure that was associated with profound decreases in CBFv, and we revealed that while the severity of the TIA initially increased with repeated exposures, it subsequently improved in parallel to an increase in the vessel density. This suggests that strategies to accelerate cerebrovascular recovery might be therapeutically beneficial in cocaine abusers.

  3. Acute total sleep deprivation potentiates cocaine-induced hyperlocomotion in mice.

    Science.gov (United States)

    Berro, L F; Santos, R; Hollais, A W; Wuo-Silva, R; Fukushiro, D F; Mári-Kawamoto, E; Costa, J M; Trombin, T F; Patti, C L; Grapiglia, S B; Tufik, S; Andersen, M L; Frussa-Filho, R

    2014-09-05

    Sleep deprivation is common place in modern society. Nowadays, people tend to self-impose less sleep in order to achieve professional or social goals. In the social context, late-night parties are frequently associated with higher availability of recreational drugs with abuse potential. Physiologically, all of these drugs induce an increase in dopamine release in the mesolimbic dopaminergic system, which leads to hyperlocomotion in rodents. Sleep deprivation also seems to play an important role in the events related to the neurotransmission of the dopaminergic system by potentiating its behavioral effects. In this scenario, the aim of the present study was to investigate the effects of total sleep deprivation (6h) on the acute cocaine-induced locomotor stimulation in male mice. Animals were sleep deprived or maintained in their home cages and subsequently treated with an acute i.p. injection of 15mg/kg cocaine or saline and observed in the open field. Total sleep deprivation for 6h potentiated the hyperlocomotion induced by acute cocaine administration. In addition, the cocaine sleep deprived group showed a decreased ratio central/total locomotion compared to the cocaine control group, which might be related to an increase in the impulsiveness of mice. Our data indicate that acute periods of sleep loss should be considered risk factors for cocaine abuse.

  4. Neuropeptide Y Y5 receptor antagonism attenuates cocaine-induced effects in mice

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Jensen, Morten; Weikop, Pia

    2012-01-01

    Rationale Several studies suggest a role for neuropeptide Y (NPY) in addiction to drugs of abuse, including cocaine. However, the NPY receptors mediating addiction-related effects remain to be determined. Objectives To explore the potential role of Y5 NPY receptors in cocaine-induced behavioural...... effects. Methods The Y5 antagonist L-152,804 and Y5-knockout (Y5-KO) mice were tested in two models of cocaine addiction-related behaviour: acute self-administration and cocaine-induced hyperactivity. We also studied effects of Y5 receptor antagonism on cocaine-induced c-fos expression and extracellular...... effects, suggesting that Y5 receptors could be a potential therapeutic target in cocaine addiction....

  5. Acute pancreatitis as initial presentation of cocaine-induced vasculitis: a case report.

    Science.gov (United States)

    Ogunbameru, Ayorinde; Jandali, Mohammed; Issa, Amer; Quwatli, Waleed; Woodlock, Timothy; Choudhry, Wajid

    2015-03-20

    Levamisole-contaminated cocaine is an increasingly reported cause of vasculitis and immunologic abnormalities in cocaine abusers. The systemic effects of vasculitis are commonly seen in the dermatologic, hematologic and renal systems but rarely the gastrointestinal system. We present an atypical case of cocaine-induced vasculitis presenting initially as an acute pancreatitis and then rapidly progressing to involve multi-organ systems over the next couple of weeks. Internists should recognize that acute pancreatitis can present as an atypical and rare initial systemic manifestation of cocaine-induced vasculitis.

  6. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat.

    Science.gov (United States)

    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

    2014-01-01

    but not with the prevention of cocaine-induced sensitization.

  7. Pharmacological blockade of either, cannabinoid CB1 or CB2 receptors, prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rats.

    Directory of Open Access Journals (Sweden)

    EDUARDO eBLANCO-CALVO

    2014-01-01

    Full Text Available Addiction to major drugs of abuse such as cocaine has been recently linked to alterations on adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulated this proliferative response since pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors by modulating not only neurogenesis but also cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation . To this end we examined if pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg or CB2 receptors (AM630, 3 mg/kg affects cell proliferation (labeled with BrdU, found in the subventricular zone (SVZ of the lateral ventricles and the dentate subgranular zone (SGZ. In addition, we measured cell apoptosis (monitored by the expression of cleaved caspase-3 and glial activation ( by analizing the expression of GFAP and Iba-1 in the striatum and hippocampus, during acute or repeated (4 days cocaine administration (20 mg/kg. Results showed that acute cocaine decreased the number of BrdU+ cells in SVZ and SGZ. In contrast, repeated cocaine reduced the number of BrdU+ cells in SVZ only. Both acute and repeated cocaine increased the number of cleaved caspase-3+, GFAP+ and Iba1+ cells in the hippocampus, an effect counteracted by AM630 or Rimonabant that increased the number of BrdU+, GFAP+ and Iba1+ cells in the hippocampus. These results indicate that changes on neurogenic, apoptotic and gliosis processes, which were produced as a consequence of repeated cocaine administration, were normalized by the pharmacological blockade of CB1 and CB2. The restoring effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with a prevention of the induction of conditioned locomotion, but not of cocaine-induced sensitization.

  8. Sulpiride, but not SCH23390, modifies cocaine-induced conditioned place preference and expression of tyrosine hydroxylase and elongation factor 1α in zebrafish.

    Science.gov (United States)

    Darland, Tristan; Mauch, Justin T; Meier, Ellen M; Hagan, Shannon J; Dowling, John E; Darland, Diane C

    2012-12-01

    Finding genetic polymorphisms and mutations linked to addictive behavior can provide important targets for pharmaceutical and therapeutic interventions. Forward genetic approaches in model organisms such as zebrafish provide a potentially powerful avenue for finding new target genes. In order to validate this use of zebrafish, the molecular nature of its reward system must be characterized. We have previously reported the use of cocaine-induced conditioned place preference (CPP) as a reliable method for screening mutagenized fish for defects in the reward pathway. Here we test if CPP in zebrafish involves the dopaminergic system by co-treating fish with cocaine and dopaminergic antagonists. Sulpiride, a potent D2 receptor (DR2) antagonist, blocked cocaine-induced CPP, while the D1 receptor (DR1) antagonist SCH23390 had no effect. Acute cocaine exposure also induced a rise in the expression of tyrosine hydroxylase (TH), an important enzyme in dopamine synthesis, and a significant decrease in the expression of elongation factor 1α (EF1α), a housekeeping gene that regulates protein synthesis. Cocaine selectively increased the ratio of TH/EF1α in the telencephalon, but not in other brain regions. The cocaine-induced change in TH/EF1α was blocked by co-treatment with sulpiride, but not SCH23390, correlating closely with the action of these drugs on the CPP behavioral response. Immunohistochemical analysis revealed that the drop in EF1α was selective for the dorsal nucleus of the ventral telencephalic area (Vd), a region believed to be the teleost equivalent of the striatum. Examination of TH mRNA and EF1α transcripts suggests that regulation of expression is post-transcriptional, but this requires further examination. These results highlight important similarities and differences between zebrafish and more traditional mammalian model organisms.

  9. Inhibition of NAALADase by 2-PMPA attenuates cocaine-induced relapse in rats: a NAAG-mGluR2/3-mediated mechanism.

    Science.gov (United States)

    Xi, Zheng-Xiong; Li, Xia; Peng, Xiao-Qing; Li, Jie; Chun, Lauren; Gardner, Eliot L; Thomas, Ajit G; Slusher, Barbara S; Ashby, Charles R

    2010-01-01

    Pharmacological activation of group II metabotropic glutamate receptors (mGluR2/3) inhibits cocaine self-administration and reinstatement of drug-seeking behavior, suggesting a possible use of mGluR2/3 agonists in the treatment of cocaine dependence. In this study, we investigated whether elevation of the endogenous mGluR2/3 ligand N-acetyl-aspartatylglutamate (NAAG) levels by the N-acetylated-alpha-linked-acidic dipeptidase inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) attenuates cocaine self-administration and cocaine-induced reinstatement of drug seeking. N-acetylated-alpha-linked-acidic dipeptidase is a NAAG degradation enzyme that hydrolyzes NAAG to N-acetylaspartate and glutamate. Systemic administration of 2-PMPA (10-100 mg/kg, i.p.) inhibited intravenous self-administration maintained by low unit doses of cocaine and cocaine (but not sucrose)-induced reinstatement of drug-seeking behavior. Microinjections of 2-PMPA (3-5 microg/side) or NAAG (3-5 microg/side) into the nucleus accumbens (NAc), but not into the dorsal striatum, also inhibited cocaine-induced reinstatement, an effect that was blocked by intra-NAc injection of LY341495, a selective mGluR2/3 antagonist. In vivo microdialysis demonstrated that 2-PMPA (10-100 mg/kg, i.p.) produced a dose-dependent reduction in both extracellular dopamine (DA) and glutamate, an effect that was also blocked by LY341495. Finally, pre-treatment with 2-PMPA partially attenuated cocaine-enhanced extracellular NAc DA, while completely blocking cocaine-enhanced extracellular NAc glutamate in rats during reinstatement testing. Intra-NAc perfusion of LY341495 blocked 2-PMPA-induced reductions in cocaine-enhanced extracellular NAc glutamate, but not DA. These findings suggest that 2-PMPA is effective in attenuating cocaine-induced reinstatement of drug-seeking behavior, likely by attenuating cocaine-induced increases in NAc DA and glutamate via pre-synaptic mGluR2/3s.

  10. Behavioral Screening for Cocaine Sensitivity in Mutagenized Zebrafish

    National Research Council Canada - National Science Library

    Tristan Darland; John E. Dowling

    2001-01-01

    .... Here, we report that zebrafish exhibit cocaine-induced conditioned place preference. In a pilot screen of 18 F generation families of mutagenized fish, we found three with abnormally low responses to cocaine...

  11. Insulin modulates cocaine-sensitive monoamine transporter function and impulsive behavior.

    Science.gov (United States)

    Schoffelmeer, Anton N M; Drukarch, Benjamin; De Vries, Taco J; Hogenboom, François; Schetters, Dustin; Pattij, Tommy

    2011-01-26

    Because insulin acutely enhances the function of dopamine transporters, the tyrosine kinase receptors activated by this hormone may modulate transporter-dependent neurochemical and behavioral effects of psychoactive drugs. In this respect, we examined the effects of insulin on exocytotic monoamine release and the efficacy of the monoamine transporter blocker cocaine in rat nucleus accumbens. Whereas insulin reduced electrically evoked exocytotic [(3)H]dopamine release in nucleus accumbens slices, the hormone potentiated the release-enhancing effect of cocaine thereon. The phosphatidylinositol 3-kinase inhibitor LY294002 abolished these effects, indicating the involvement of insulin receptors. Similar insulin effects were observed on the release of [(3)H]norepinephrine in nucleus accumbens slices, but not on that of [(3)H]serotonin, and were also apparent in medial prefrontal cortex slices. As might then be expected, insulin also potentiated the dopamine and norepinephrine release-enhancing effects of the selective monoamine uptake inhibitors GBR12909 and desmethylimipramine, respectively. In subsequent behavioral experiments, we investigated the role of insulin in motor impulsivity that depends on monoamine neurotransmission in the nucleus accumbens. Intracranial administration of insulin in the nucleus accumbens alone reduced premature responses in the five-choice serial reaction time task and enhanced the stimulatory effect of peripheral cocaine administration on impulsivity, resembling the observed neurochemical effects of the hormone. In contrast, cocaine-induced locomotor activity remained unchanged by intra-accumbal insulin application. These data reveal that insulin presynaptically regulates cocaine-sensitive monoamine transporter function in the nucleus accumbens and, as a consequence, impulsivity. Therefore, insulin signaling proteins may represent targets for the treatment of inhibitory control deficits such as addictive behaviors.

  12. Activation of serotonin 5-HT2C receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-dependent mice

    Science.gov (United States)

    Zhang, Gongliang; Wu, Xian; Zhang, Yong-Mei; Liu, Huan; Jiang, Qin; Pang, Gang; Tao, Xinrong; Dong, Liuyi; Stackman, Robert W.

    2015-01-01

    Opioid abuse and dependence have evolved into an international epidemic as a significant clinical and social problem with devastating consequences. Repeated exposure to the opioid, for example morphine, can induce profound, long-lasting behavioral sensitization and physical dependence, which are thought to reflect neuroplasticity in neural circuitry. Central serotonin (5-HT) neurotransmission participates in the development of dependence on and the expression of withdrawal from morphine. Serotonin 5-HT2C receptor (5-HT2CR) agonists suppress psychostimulant nicotine or cocaine-induced behavioral sensitization and drug-seeking behavior; however, the impact of 5-HT2CR agonists on behaviors relevant to opioid abuse and dependence has not been reported. In the present study, the effects of 5-HT2CR activation on the behavioral sensitization and naloxone-precipitated withdrawal symptoms were examined in mice underwent repeated exposure to morphine. Male mice received morphine (10 mg/kg, s.c.) to develop behavioral sensitization. Lorcaserin, a 5-HT2CR agonist, prevented the induction and expression, but not the development, of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. Pretreatment of lorcaserin, or the positive control clonidine (an alpha 2-adrenoceptor agonist), ameliorated the naloxone-precipitated withdrawal symptoms. SB 242084, a selective 5-HT2CR antagonist, prevented the lorcaserin-mediated suppression of behavioral sensitization and withdrawal. Chronic morphine treatment was associated with an increase in the expression of 5-HT2CR protein in the ventral tegmental area, locus coeruleus and nucleus accumbens. These findings suggest that 5-HT2CR can modulate behavioral sensitization and withdrawal in morphine-dependent mice, and the activation of 5-HT2CR may represent a new avenue for the treatment of opioid addiction. PMID:26432939

  13. Cocaine-induced vasculitis with cutaneous manifestation: A recurrent episode after 2 years

    Directory of Open Access Journals (Sweden)

    Thein Swe

    2016-01-01

    Full Text Available Cocaine is a popular recreational drug in the United States, and up to 70% of the seized cocaine contains levamisole which is an antihelminthic that can cause cutaneous vasculitis with necrosis and positive antineutrophil cytoplasmic antibodies (ANCAs. Here, we report a unique case of recurrent cocaine-induced vasculitis in a patient who smokes cocaine for more than 20 years. A 38-year-old woman complained of painful erythematous rash in her right arm and right thigh which appeared some hours after smoking cocaine. Physical examination revealed tender, erythematous base, retiform purpura with necrosis and bullae. Serological test showed high atypical perinuclear ANCA titer of 1:320 and antimyeloperoxidase antibody level of 20.4 U/mL. Cocaine-induced vasculitis should be one of the differential diagnoses in cocaine abusers who present with painful rash and areas of necrosis. Early diagnosis is important since it is an emerging public health concern.

  14. Mephedrone interactions with cocaine: prior exposure to ‘bath salt’ constituent enhances cocaine-induced locomotor activation in rats

    Science.gov (United States)

    Gregg, Ryan A.; Tallarida, Christopher S.; Reitz, Allen B.; Rawls, Scott M.

    2014-01-01

    Concurrent use of mephedrone (4-methylmethcathinone) (MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity following pretreatment with cocaine or MEPH than following pretreatment with saline. METH challenge produced greater locomotor activity following METH pretreatment than following saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bi-directional and did not extend to METH, suggesting the phenomenon is sensitive to specific psychostimulants. PMID:24126218

  15. Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats.

    Science.gov (United States)

    Gregg, Ryan A; Tallarida, Christopher S; Reitz, Allen B; Rawls, Scott M

    2013-12-01

    Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants.

  16. The 2-methoxy methyl analogue of salvinorin A attenuates cocaine-induced drug seeking and sucrose reinforcements in rats.

    Science.gov (United States)

    Morani, Aashish S; Ewald, Amy; Prevatt-Smith, Katherine M; Prisinzano, Thomas E; Kivell, Bronwyn M

    2013-11-15

    κ Opioid receptor activation by traditional arylacetamide agonists and the novel neoclerodane diterpene κ opioid receptor agonist Salvinorin A (Sal A) results in attenuation of cocaine-seeking behavior in pre-clinical models of addiction. However, adverse effects such as sedation, depression and aversion limit their clinical utility. The Sal A analogue, 2-methoxy-methyl salvinorin B (MOM Sal B) is a longer acting Sal A analogue with high affinity for κ opioid receptors. In this study, we tested MOM Sal B for its ability to modulate cocaine-seeking behavior in rats. MOM Sal B (0.3mg/kg) successfully attenuated cocaine-seeking but also attenuated sucrose reinforcement. No change in activity was observed in either cocaine-induced hyperactivity or spontaneous open field activity tests but increased immobility and decreased swimming times in the forced swim test were observed. This study indicates that κ opioid receptor activation by more potent Sal A analogues modulates cocaine-seeking behavior non-selectively without causing sedation, suggesting an improved side effects profile. However, pro-depressive effects are seen, which may limit the therapeutic potential of this compound. Future studies with Sal A analogues having affinities at other opioid receptors are warranted as they have the potential to identify compounds having effective anti-addiction properties.

  17. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

    Science.gov (United States)

    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando

    2014-01-01

    locomotion but not with the prevention of cocaine-induced sensitization. PMID:24409127

  18. The Bermuda Triangle of Cocaine-Induced Neuroadaptations

    OpenAIRE

    Marina E Wolf

    2010-01-01

    Activation of medium spiny neurons (MSN) of the nucleus accumbens is critical for goal-directed behaviors including cocaine seeking. Studies in cocaine-experienced rodents have revealed three major categories of neuroadaptations that influence the ability of glutamate inputs to activate MSN: changes in synaptic AMPA receptor levels, changes in extracellular non-synaptic glutamate levels, and changes in MSN intrinsic membrane excitability. Most studies have focused on one of these adaptations....

  19. The Bermuda Triangle of cocaine-induced neuroadaptations.

    Science.gov (United States)

    Wolf, Marina E

    2010-09-01

    Activation of medium spiny neurons (MSNs) of the nucleus accumbens is critical for goal-directed behaviors including cocaine seeking. Studies in cocaine-experienced rodents have revealed three major categories of neuroadaptations that influence the ability of glutamate inputs to activate MSNs: changes in synaptic AMPA receptor levels, changes in extracellular non-synaptic glutamate levels and changes in MSN intrinsic membrane excitability. Most studies have focused on one of these adaptations. This review will consider the possibility that they are causally related and speculate about how time-dependent changes in their interactions may regulate MSN output during early and late withdrawal from repeated cocaine exposure.

  20. Dopamine-sensitive signaling mediators modulate psychostimulant-induced ultrasonic vocalization behavior in rats.

    Science.gov (United States)

    Williams, Stacey N; Undieh, Ashiwel S

    2016-01-01

    The mesolimbic dopamine system plays a major role in psychostimulant-induced ultrasonic vocalization (USV) behavior in rodents. Within this system, psychostimulants elevate synaptic concentrations of dopamine thereby leading to exaggerated activation of postsynaptic dopamine receptors within the D1-like and D2-like subfamilies. Dopamine receptor stimulation activate several transmembrane signaling systems and cognate intracellular mediators; downstream activation of transcription factors then conveys the information from receptor activation to appropriate modulation of cellular and physiologic functions. We previously showed that cocaine-induced USV behavior was associated with enhanced expression of the neurotrophin BDNF. Like cocaine, amphetamine also increases synaptic dopamine levels, albeit primarily through facilitating dopamine release. Therefore, in the present study we investigated whether amphetamine and cocaine similarly activate dopamine-linked signaling cascades to regulate intracellular mediators leading to induction of USV behavior. The results show that amphetamine increased the emission of 50 kHz USVs and this effect was blocked by SCH23390, a D1 receptor antagonist. Similar to cocaine, amphetamine increased BDNF protein expression in discrete brain regions, while pretreatment with K252a, a trkB neurotrophin receptor inhibitor, significantly reduced amphetamine-induced USV behavior. Inhibition of cyclic-AMP/PKA signaling with H89 or inhibition of PLC signaling with U73122 significantly blocked both the acute and subchronic amphetamine-induced USV behavior. In contrast, pharmacologic inhibition of either pathway enhanced cocaine-induced USV behavior. Although cocaine and amphetamine similarly modulate neurotrophin expression and USV, the molecular mechanisms by which these psychostimulants differentially activate dopamine receptor subtypes or other monoaminergic systems may be responsible for the distinct aspects of behavioral responses.

  1. Applying incentive sensitization models to behavioral addiction

    DEFF Research Database (Denmark)

    Rømer Thomsen, Kristine; Fjorback, Lone; Møller, Arne

    2014-01-01

    The incentive sensitization theory is a promising model for understanding the mechanisms underlying drug addiction, and has received support in animal and human studies. So far the theory has not been applied to the case of behavioral addictions like Gambling Disorder, despite sharing clinical...... symptoms and underlying neurobiology. We examine the relevance of this theory for Gambling Disorder and point to predictions for future studies. The theory promises a significant contribution to the understanding of behavioral addiction and opens new avenues for treatment....

  2. Applying incentive sensitization models to behavioral addiction

    DEFF Research Database (Denmark)

    Rømer Thomsen, Kristine; Fjorback, Lone; Møller, Arne

    2014-01-01

    The incentive sensitization theory is a promising model for understanding the mechanisms underlying drug addiction, and has received support in animal and human studies. So far the theory has not been applied to the case of behavioral addictions like Gambling Disorder, despite sharing clinical...

  3. Cocaine-induced renal infarction: report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Nosrati Saeid M

    2005-09-01

    Full Text Available Abstract Background Cocaine abuse has been known to have detrimental effects on the cardiovascular system. Its toxicity has been associated with myocardial ischemia, cerebrovascular accidents and mesenteric ischemia. The pathophysiology of cocaine-related renal injury is multifactorial and involves renal hemodynamic changes, alterations in glomerular matrix synthesis, degradation and oxidative stress, and possibly induction of renal atherogenesis. Renal infarction as a result of cocaine exposure, however, is rarely reported in the literature. Case presentation A 48 year-old male presented with a four-day history of severe right flank pain following cocaine use. On presentation, he was tachycardic, febrile and had severe right costovertebral angle tenderness. He had significant proteinuria, leukocytosis and elevated serum creatinine and lactate dehydrogenase. Radiographic imaging studies as well as other screening tests for thromboembolic events, hypercoagulability states, collagen vascular diseases and lipid disorders were suggestive of Cocaine-Induced Renal Infarction (CIRI by exclusion. Conclusion In a patient with a history of cocaine abuse presenting with fevers and flank pain suggestive of urinary tract infection or nephrolithiasis, cocaine-induced renal infarction must be considered in the differential diagnosis. In this article, we discuss the prior reported cases of CIRI and thoroughly review the literature available on this disorder. This is important for several reasons. First, it will allow us to discuss and elaborate on the mechanism of renal injury caused by cocaine. In addition, this review will demonstrate the importance of considering the diagnosis of CIRI in a patient with documented cocaine use and an atypical presentation of acute renal injury. Finally, we will emphasize the need for a consensus on optimal treatment of this disease, for which therapy is not yet standardized.

  4. EGCG通过 PICK1抑制可卡因小鼠的自发活动机制研究%EGC G Inhibits Cocaine Induced Locomotor Activity via PICK1

    Institute of Scientific and Technical Information of China (English)

    蔡飞; 李彩蓉; 袁鑫; 王江华; 蔡雪洲

    2013-01-01

    Objective The aim of this study was to examine the effect of EGCG on cocaine induced lo-comotor activity in mice ,and to explore its mechanism of action .Methods EGCG was pretreated before cocaine which was used by intraperitoneal injection .Locomotor activity was detected by behavioral test and the expres-sion of PICK1 protein in the nucleus accumbens ( NAc) was tested by Western blot .Results EGCG can inhibit cocaine induced locomotor activity ,and reduce the expression of PICK 1 protein in NAc.Conclusion EGCG may be important pharmocological effect to prevent cocaine induced drug abuse ,which may be related to inhibition of nucleus accumbens PICK 1 protein expression .%目的:观察EGCG对可卡因小鼠自发活动的影响,并探讨其作用机制。方法通过小鼠腹腔注射可卡因,预先给予EGCG进行干预,采用行为学检测小鼠的自发活动,采用Western blot 的方法检测小鼠伏隔核PICK1蛋白的表达。结果EGCG可抑制可卡因所致小鼠自发活动的增强,并且减少小鼠伏隔核 PICK1蛋白表达。结论EGCG可能对可卡因所致的药物成瘾有防治作用,其作用可能与抑制伏隔核PICK1蛋白表达有关。

  5. Central serotonin(2B) receptor blockade inhibits cocaine-induced hyperlocomotion independently of changes of subcortical dopamine outflow.

    Science.gov (United States)

    Devroye, Céline; Cathala, Adeline; Di Marco, Barbara; Caraci, Filippo; Drago, Filippo; Piazza, Pier Vincenzo; Spampinato, Umberto

    2015-10-01

    The central serotonin2B receptor (5-HT2BR) is currently considered as an interesting pharmacological target for improved treatment of drug addiction. In the present study, we assessed the effect of two selective 5-HT2BR antagonists, RS 127445 and LY 266097, on cocaine-induced hyperlocomotion and dopamine (DA) outflow in the nucleus accumbens (NAc) and the dorsal striatum of freely moving rats. The peripheral administration of RS 127445 (0.16 mg/kg, i.p.) or LY 266097 (0.63 mg/kg, i.p.) significantly reduced basal DA outflow in the NAc shell, but had no effect on cocaine (10 mg/kg, i.p.)-induced DA outflow in this brain region. Also, RS 127445 failed to modify both basal and cocaine-induced DA outflow in the NAc core and the dorsal striatum. Conversely, both 5-HT2BR antagonists reduced cocaine-induced hyperlocomotion. Furthermore, RS 127445 as well as the DA-R antagonist haloperidol (0.1 mg/kg, i.p.) reduced significantly the late-onset hyperlocomotion induced by the DA-R agonist quinpirole (0.5 mg/kg, s.c.). Altogether, these results demonstrate that 5-HT2BR blockade inhibits cocaine-induced hyperlocomotion independently of changes of subcortical DA outflow. This interaction takes place downstream to DA neurons and could involve an action at the level of dorsostriatal and/or NAc DA transmission, in keeping with the importance of these brain regions in the behavioural responses of cocaine. Overall, this study affords additional knowledge into the regulatory control exerted by the 5-HT2BR on ascending DA pathways, and provides additional support to the proposed role of 5-HT2BRs as a new pharmacological target in drug addiction.

  6. Pretreatment with group I metabotropic glutamate receptors antagonists attenuates lethality induced by acute cocaine overdose and expression of sensitization to hyperlocomotor effect of cocaine in mice.

    Science.gov (United States)

    Kotlinska, Jolanta; Bochenski, Marcin

    2011-01-01

    Cocaine abuse and dependence is a worldwide health problem. However, there are no currently approved medications to reduce cocaine abuse/relapse and toxicity. The aim of the present study was to test, whether group I metabotropic glutamate receptors (mGluRs) antagonists (mGluR1 and mGluR5) differentially regulate toxic versus behavioral effects of cocaine, both phenomena relevant to the psychopathology of cocaine addiction in humans. In the present study, we assessed the impact of mGluR1 antagonist-EMQMCM and mGluR5 antagonist-MTEP on the cocaine-induced lethality and the expression of sensitization to hyperlocomotor effect of cocaine in mice. Our study indicated that EMQMCM and MTEP, both substances at the doses of 5 and 10 mg/kg (but not 2.5 mg/kg), decreased cocaine-induced lethality produced by 75 mg/kg of cocaine, which was given acutely. The effect of EMQMCM was dose-dependent, and this compound at the dose of 10 mg/kg almost completely abolished the lethality induced by cocaine. MTEP reduced this cocaine effect at the doses of 5 and 10 mg/kg, equally. Furthermore, EMQMCM (1.25-5 mg/kg) at the doses of 2.5 and 5.0 mg/kg, and MTEP (2.5-10 mg/kg) only at the highest dose of 10 mg/kg, significantly reduced the expression of cocaine-induced (10 mg/kg) behavioral sensitization. Our results suggest that stimulation of mGluR1 and mGluR5 is involved in lethal effect of cocaine overdose and cocaine seeking behavior evaluated in behavioral sensitization test. However, the participation of mGluR1 in these cocaine effects seems to be dominant. Therefore, antagonists showing preferences towards mGluR1 might be useful in therapy of cocaine toxicity and abuse.

  7. Effects of disulfiram and dopamine beta-hydroxylase knockout on cocaine-induced seizures

    Science.gov (United States)

    Gaval-Cruz, Meriem; Schroeder, Jason P.; Liles, L. Cameron; Javors, Martin A.; Weinshenker, David

    2008-01-01

    The antialcoholism drug disulfiram has shown recent promise as a pharmacotherapy for treating cocaine dependence, probably via inhibition of dopamine β-hydroxylase (DBH), the enzyme that catalyzes the conversion of dopamine (DA) to norepinephrine (NE). We previously showed that DBH knockout (Dbh -/-) mice, which lack NE, are susceptible to seizures and are hypersensitive to the psychomotor, rewarding, and aversive effects of cocaine, suggesting that disulfiram might exacerbate cocaine-induced seizures (CIS) by inhibiting DBH. To test this, we examined CIS in wild-type and Dbh -/- mice following administration of disulfiram or the selective DBH inhibitor nepicastat. We found that Dbh genotype had no effect on CIS probability or frequency, whereas disulfiram, but not nepicastat, increased the probability of having CIS in both wild-type and Dbh -/- mice. Both disulfiram and nepicastat increased CIS frequency in wild-type but not Dbh -/- mice. There were no genotype or treatment effects on serum cocaine levels, except for an increase in disulfiram-treated Dbh -/- mice at the highest dose of cocaine. These results suggest that disulfiram enhances CIS via two distinct mechanisms: it both increases CIS frequency by inhibiting DBH and increases CIS frequency in a DBH-independent manner. PMID:18329701

  8. Behavioral Control and Reward Sensitivity in Adolescents' Risk Taking Behavior : A Longitudinal TRAILS Study

    NARCIS (Netherlands)

    Peeters, Margot; Oldehinkel, Tineke; Vollebergh, Wilma

    2017-01-01

    Neurodevelopmental theories of risk behavior hypothesize that low behavioral control in combination with high reward sensitivity explains adolescents' risk behavior. However, empirical studies examining this hypothesis while including actual risk taking behavior in adolescence are lacking. In this

  9. Cocaine induces a reversible stomatocytosis of red blood cells and increases blood viscosity.

    Science.gov (United States)

    Cagienard, F; Schulzki, T; Furlong, P; Reinhart, W H

    2013-01-01

    Severe side effects of cocaine consumption are vasoocclusive events such as myocardial infarction and stroke. We have hypothesized that cocaine could affect red blood cells (RBCs) and alter the rheological behaviour of blood. Heparinized blood from healthy volunteers was incubated with a final hematocrit of 45% with increasing cocaine concentrations: 0, 10, 100, 1000, and 10'000 μmol/L plasma. Time dependence of the shape change was tested in phosphate buffered saline containing cocaine. RBCs were fixed in 1% glutaraldehyde for morphological analysis. Blood viscosity was measured with a Couette Viscometer (Contraves LS 30) at 37°C and a shear rate of 69.5 s⁻¹. RBC aggregation was assessed with a Myrenne aggregometer. Cocaine induced a dose-dependent stomatocytic shape transformation of RBCs, which was more pronounced in buffer than in plasma (plasma protein binding of the drug). Stomatocytosis occurs when a drug intercalates preferentially in the inner half of the membrane lipid bilayer. It was a time-dependent process with two components, an almost instant shape change occurring within 1 s, followed by a gradual further shape change during 10 min. Stomatocytosis was reversible by resuspension of the RBCs in cocaine-free buffer. This stomatocytic shape change increased whole blood viscosity at high shear rate from 5.69±0.31 mPa.s to 6.39±0.34 mPa.s for control and 10'000 μmol/L cocaine, respectively (p<0.01). RBC aggregation was not affected by the shape change. These effects occurred at a cocaine concentration, which is several-fold above those measured in vivo. Therefore, it is unlikely that hemorheological factors are involved in vascular events after cocaine consumption.

  10. Behavioral Control and Reward Sensitivity in Adolescents' Risk Taking Behavior: A Longitudinal TRAILS Study

    OpenAIRE

    Peeters, Margot; Oldehinkel, Tineke; Vollebergh, Wilma

    2017-01-01

    Neurodevelopmental theories of risk behavior hypothesize that low behavioral control in combination with high reward sensitivity explains adolescents’ risk behavior. However, empirical studies examining this hypothesis while including actual risk taking behavior in adolescence are lacking. In this study we tested whether the imbalance between behavioral control and reward sensitivity underlies risk taking behavior in adolescence, using a nationally representative longitudinal sample of 715 ad...

  11. Repression-Sensitization and Health Behavior.

    Science.gov (United States)

    Gayton, William F.; And Others

    1978-01-01

    Examined relationship between repression-sensitization (R-S) and visits to prison infirmary for males during a one-year period. Main effect for R-S dimension was significant for total number of visits, number of medically justified visits, and number of medically unjustified visits. Sensitizers had significantly more visits than repressors.…

  12. Repression-Sensitization and Health Behavior.

    Science.gov (United States)

    Gayton, William F.; And Others

    1978-01-01

    Examined relationship between repression-sensitization (R-S) and visits to prison infirmary for males during a one-year period. Main effect for R-S dimension was significant for total number of visits, number of medically justified visits, and number of medically unjustified visits. Sensitizers had significantly more visits than repressors.…

  13. Loss of D2 dopamine receptor function modulates cocaine-induced glutamatergic synaptic potentiation in the ventral tegmental area.

    Science.gov (United States)

    Madhavan, Anuradha; Argilli, Emanuela; Bonci, Antonello; Whistler, Jennifer L

    2013-07-24

    Potentiation of glutamate responses is a critical synaptic response to cocaine exposure in ventral tegmental area (VTA) neurons. However, the mechanism by which cocaine exposure promotes potentiation of NMDA receptors (NMDARs) and subsequently AMPA receptors (AMPARs) is not fully understood. In this study we demonstrate that repeated cocaine treatment causes loss of D2 dopamine receptor functional responses via interaction with lysosome-targeting G-protein-associated sorting protein1 (GASP1). We also show that the absence of D2 downregulation in GASP1-KO mice prevents cocaine-induced potentiation of NMDAR currents, elevation of the AMPA/NMDA ratio, and redistribution of NMDAR and AMPAR subunits to the membrane. As a pharmacological parallel, coadministration of the high-affinity D2 agonist, aripiprazole, reduces not only functional downregulation of D2s in response to cocaine but also potentiation of NMDAR and AMPAR responses in wild-type mice. Together these data suggest that functional loss of D2 receptors is a critical mechanism mediating cocaine-induced glutamate plasticity in VTA neurons.

  14. 丙戌酸钠对小鼠甲基苯丙胺和可卡因行为敏化的影响%Effects of Valproate on Methamphetamine and Cocaine Behavioral Sensitization of Mice

    Institute of Scientific and Technical Information of China (English)

    金科

    2012-01-01

    目的:探讨丙戌酸钠(VPA)对甲基苯丙胺(METH)和可卡因致小鼠行为敏化的影响.方法:在甲基苯丙胺和可卡因行为敏化模型中测定小鼠自主活动,研究甲基苯丙胺和可卡因行为敏化的形成、单次或多次丙戌酸钠对急性甲基苯丙胺和可卡因致小鼠高活动性的影响、丙戌酸钠对甲基苯丙胺和可卡因行为敏化的影响.结果:①甲基苯丙胺或可卡因处理可增强小鼠的自主活动,且随着给药次数增加而增强;②丙戊酸钠对急性甲基苯丙胺和可卡因引起的高活动性没有影响;③甲基苯丙胺和可卡因处理后的每小时自发活动量分别为(15 642.7±286.4)和(14 358.9±273.6),而丙戊酸钠预处理后可抑制甲基苯丙胺的行为敏化的形成,对可卡因无影响.结论:甲基苯丙胺和可卡因在行为敏化的形成过程中具有不同的神经机制.这两种精神兴奋剂之间所存在的微小差异可能具有一定的临床意义.%Objective: To explore the effects of valproate on methamphetamine and cocaine behavioral sensitization of mice. Methods: The locomotor activity was measured in the animal model of methamphetamine and cocaine behavioral sensitization. The relative experiments were carried out as below: the influence of methamphetamine and cocaine on behavioral sensitization, the influence of single or multiple injections of valproate on methamphetamine and cocaine induced high-activity, and the influence of valproate on the behavioral sensitization of methamphetamine and cocaine induced high-activity. Results: ①Both methamphetamine and cocaine can enhance the locomotor activity, and the effect increased in pace with the administration numbers; ②valproate had no effect on the high activity resulted by acute methamphetamine and cocaine; ③The locomotor activities in an hour after the treatment of methamphetamine or cocaine were (15 642. 7 ± 286. 4) and (14 358. 9 ± 273. 6) separately, while valproate only

  15. Metabotropic glutamate receptor I (mGluR1) antagonism impairs cocaine-induced conditioned place preference via inhibition of protein synthesis.

    Science.gov (United States)

    Yu, Fei; Zhong, Peng; Liu, Xiaojie; Sun, Dalong; Gao, Hai-Qing; Liu, Qing-Song

    2013-06-01

    Antagonism of group I metabotropic glutamate receptors (mGluR1 and mGluR5) reduces behavioral effects of drugs of abuse, including cocaine. However, the underlying mechanisms remain poorly understood. Activation of mGluR5 increases protein synthesis at synapses. Although mGluR5-induced excessive protein synthesis has been implicated in the pathology of fragile X syndrome, it remains unknown whether group I mGluR-mediated protein synthesis is involved in any behavioral effects of drugs of abuse. We report that group I mGluR agonist DHPG induced more pronounced initial depression of inhibitory postsynaptic currents (IPSCs) followed by modest long-term depression (I-LTD) in dopamine neurons of rat ventral tegmental area (VTA) through the activation of mGluR1. The early component of DHPG-induced depression of IPSCs was mediated by the cannabinoid CB1 receptors, while DHPG-induced I-LTD was dependent on protein synthesis. Western blotting analysis indicates that mGluR1 was coupled to extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) signaling pathways to increase translation. We also show that cocaine conditioning activated translation machinery in the VTA via an mGluR1-dependent mechanism. Furthermore, intra-VTA microinjections of mGluR1 antagonist JNJ16259685 and protein synthesis inhibitor cycloheximide significantly attenuated or blocked the acquisition of cocaine-induced conditioned place preference (CPP) and activation of translation elongation factors. Taken together, these results suggest that mGluR1 antagonism inhibits de novo protein synthesis; this effect may block the formation of cocaine-cue associations and thus provide a mechanism for the reduction in CPP to cocaine.

  16. Cocaine activates Rac1 to control structural and behavioral plasticity in caudate putamen.

    Science.gov (United States)

    Li, Juan; Zhang, Lei; Chen, Zhenzhong; Xie, Minjuan; Huang, Lu; Xue, Jinhua; Liu, Yutong; Liu, Nuyun; Guo, Fukun; Zheng, Yi; Kong, Jiming; Zhang, Lin; Zhang, Lu

    2015-03-01

    Repeated exposure to cocaine was previously found to cause sensitized behavioral responses and structural remodeling on medium spiny neurons of the nucleus accumbens (NAc) and caudate putamen (CPu). Rac1 has emerged as a key integrator of environmental cues that regulates dendritic cytoskeletons. In this study, we investigated the role of Rac1 in cocaine-induced dendritic and behavioral plasticity in the CPu. We found that Rac1 activation was reduced in the NAc but increased in the CPu following repeated cocaine treatment. Inhibition of Rac1 activity by a Rac1-specific inhibitor NSC23766, overexpression of a dominant negative mutant of Rac1 (T17N-Rac1) or local knockout of Rac1 attenuated the cocaine-induced increase in dendrites and spine density in the CPu, whereas overexpression of a constitutively active Rac1 exert the opposite effect. Moreover, NSC23766 reversed the increased number of asymmetric spine synapses in the CPu following chronic cocaine exposure. Downregulation of Rac1 activity likewise attenuates behavioral reward responses to cocaine exposure, with activation of Rac1 producing the opposite effect. Thus, Rac1 signaling is differentially regulated in the NAc and CPu after repeated cocaine treatment, and induction of Rac1 activation in the CPu is important for cocaine exposure-induced dendritic remodeling and behavioral plasticity.

  17. Sigma1 receptor ligands and related neuroactive steroids interfere with the cocaine-induced state of memory.

    Science.gov (United States)

    Romieu, Pascal; Lucas, Morgan; Maurice, Tangui

    2006-07-01

    The present series of experiments examined the involvement of the sigma(1) receptor and related neuroactive steroids in the memory state induced by a very low dose of cocaine. Using a modified passive avoidance procedure in mice, we examined whether cocaine induces state-dependent (StD) learning. Animals trained and tested with saline or the same dose of cocaine (0.1 or 0.3 mg/kg) showed correct retention, measured using two independent parameters: the retention latency and a ratio between the retention latency and the last training latency. Animals trained with cocaine (0.1 mg/kg) and tested with saline or cocaine (0.03, 0.3 mg/kg), or trained with saline and tested with cocaine, showed altered retention parameters, demonstrating that StD occurred. Therefore, cocaine administered before training produced a chemical state used as an endogenous cue to insure optimal retention. Since sigma(1) receptor activation is an important event during the acquisition of cocaine reward, we tested several sigma(1) ligands and related neurosteroids. The sigma(1) agonist igmesine or antagonist BD1047 failed to produce StD, but modified the cocaine state. Among neuroactive steroids, pregnanolone and allopregnanolone, positive modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor, produced StD. However, steroids also acting as sigma(1) agonists, dehydroepiandrosterone (3beta-hydroxy-5alpha-androsten-17-one (DHEA)), pregnenolone, or antagonist, progesterone, failed to induce StD but modified the cocaine state. Furthermore, optimal retention was observed with mice trained with (igmesine or DHEA)+cocaine and tested with a higher dose of cocaine, or with mice trained with (BD1047 or progesterone)+cocaine and tested with vehicle. This study demonstrated that: (i) low doses of cocaine induce a chemical state/memory trace sustaining StD; (ii) modulation of the sigma(1) receptor activation, although insufficient to provoke StD, modulates the cocaine state; (iii) neuroactive

  18. Sleep deprivation impairs the extinction of cocaine-induced environmental conditioning in mice.

    Science.gov (United States)

    Berro, L F; Hollais, A W; Patti, C L; Fukushiro, D F; Mári-Kawamoto, E; Talhati, F; Costa, J M; Zanin, K A; Lopes-Silva, L B; Ceccon, L M; Santos, R; Procópio-Souza, R; Trombin, T F; Yokoyama, T S; Wuo-Silva, R; Tufik, S; Andersen, M L; Frussa-Filho, R

    2014-09-01

    Persistence of a drug-environment conditioning induced by repeated psychostimulant treatment is thought to play a key role in the addictive cycle. In addition, sleep disorders are a common feature in patients with addictive disorders. Sleep deprivation shares similar neurobiological effects with psychostimulants. Therefore, we investigated whether sleep deprivation would impair the extinction of previously established conditioning between the drug effect and the environmental cues. Four cohorts of male adult mice underwent a behavioral sensitization procedure pairing drug (cocaine at 15 mg/kg, i.p.) or saline with environment (open-field apparatus). The extinction of conditioned locomotion was evaluated after control (home-cage maintained) or sleep deprivation (gentle handling method for 6h) conditions. Sleep deprivation both postponed the initiation and impaired the completeness of extinction of the conditioned locomotion promoted by previous drug-environment conditioning in cocaine-sensitized animals. While the cocaine control group required 5 free-drug sessions of exposure to the open-field apparatus to complete extinction of conditioned locomotion, the cocaine pre-treated group that experienced sleep deprivation before each extinction session still significantly differed from its respective control group on Day 5 of extinction. The possibility that the sleep condition can influence the extinction of a long-lasting association between drug effects and environmental cues can represent new outcomes for clinically relevant phenomena.

  19. The inhibition of cocaine-induced locomotor activity by CART 55-102 is lost after repeated cocaine administration.

    Science.gov (United States)

    Job, Martin O; Shen, Li L; Kuhar, Michael J

    2013-08-29

    CART peptide is known for having an inhibitory effect on cocaine- and dopamine-mediated actions after acute administration of cocaine and dopamine. In this regard, it is postulated to be a homeostatic, regulatory factor on dopaminergic activity in the nucleus accumbens (NAc). However, there is no data on the effect of CART peptide after chronic administration of cocaine, and this study addresses this. It was found that CART peptide blunted cocaine-induced locomotion (LMA) after acute administration of cocaine, as expected, but it did not affect cocaine-mediated LMA after chronic administration of cocaine. The loss of CART peptide's inhibitory effect did not return for up to 9 weeks after stopping the repeated cocaine administration. It may not be surprising that homeostatic regulatory mechanisms in the NAc are lost after repeated cocaine administration, and that this may be a mechanism in the development of addiction.

  20. Cocaine-induced Psychosis and Brain-derived Neurothrophic Factor in Patients with Cocaine Dependence: Report of Two Cases

    Science.gov (United States)

    Roncero, Carlos; Palma-Álvarez, Raul Felipe; Ros-Cucurull, Elena; Barral, Carmen; Gonzalvo, Begoña; Corominas-Roso, Margarida; Casas, Miguel; Grau-López, Lara

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) is linked to numerous brain functions. In addition, BDNF alterations contribute to neurological, mental, and addictive disorders. Cocaine dependence has received much attention recently due to its prevalence and psychological effects. Symptoms of psychosis are one of the most serious adverse events precipitated by cocaine use. It is particularly important to identify patients at risk of developing cocaine-induced psychosis (CIP). We described two cases of patients with cocaine dependence who presented with CIP and had changes in their BDNF levels during the psychotic episode. BDNF levels were initially low in both patients, and then decreased by more than 50% in association with CIP. The relationship between BDNF and psychosis is described in the literature. These cases revealed that BDNF levels decreased during a CIP episode and, thus, it is necessary to investigate BDNF and its relationship with CIP further. PMID:26792050

  1. Exposure to repeated immobilization stress inhibits cocaine-induced increase in dopamine extracellular levels in the rat ventral tegmental area.

    Science.gov (United States)

    Sotomayor-Zárate, Ramón; Abarca, Jorge; Araya, Katherine A; Renard, Georgina M; Andrés, María E; Gysling, Katia

    2015-11-01

    A higher vulnerability to drug abuse has been observed in human studies of individuals exposed to chronic or persistent stress, as well as in animal models of drug abuse. Here, we explored the effect of repeated immobilization stress on cocaine-induced increase in dopamine extracellular levels in VTA and its regulation by corticotropin-releasing factor (CRF) and GABA systems. Cocaine (10mg/Kg i.p.) induced an increase of VTA DA extracellular levels in control rats. However, this effect was not observed in repeated stress rats. Considering the evidence relating stress with CRF, we decided to perfuse CRF and CP-154526 (selective antagonist of CRF1 receptor) in the VTA of control and repeated stress rats, respectively. We observed that perfusion of 20μM CRF inhibited the increase of VTA DA extracellular levels induced by cocaine in control rats. Interestingly, we observed that in the presence of 10μM CP-154526, cocaine induced a significant increase of VTA DA extracellular levels in repeated stress rats. Regarding the role of VTA GABA neurotransmission, cocaine administration induced a significant increase in VTA GABA extracellular levels only in repeated stress rats. Consistently, cocaine was able to increase VTA DA extracellular levels in repeated stress rats when 100μM bicuculline, an antagonist of GABAA receptor, was perfused intra VTA. Thus, both CRF and GABA systems are involved in the lack of response to cocaine in the VTA of repeated stress rats. It is tempting to suggest that the loss of response in VTA dopaminergic neurons to cocaine, after repeated stress, is due to an interaction between CRF and GABA systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. N-acetyl cysteine mitigates the acute effects of cocaine-induced toxicity in astroglia-like cells.

    Directory of Open Access Journals (Sweden)

    Ramesh B Badisa

    Full Text Available Cocaine has a short half-life of only about an hour but its effects, predominantly on the central nervous system (CNS, are fairly long-lasting. Of all cells within the CNS, astrocytes may be the first to display cocaine toxicity owing to their relative abundance in the brain. Cocaine entry could trigger several early response changes that adversely affect their survival, and inhibiting these changes could conversely increase their rate of survival. In order to identify these changes and the minimal concentrations of cocaine that can elicit them in vitro, rat C6 astroglia-like cells were treated with cocaine (2-4 mM for 1h and assayed for alterations in gross cell morphology, cytoplasmic vacuolation, viability, reactive oxygen species (ROS generation, glutathione (GSH levels, cell membrane integrity, F-actin cytoskeleton, and histone methylation. We report here that all of the above identified features are significantly altered by cocaine, and may collectively represent the key pathology underlying acute toxicity-mediated death of astroglia-like cells. Pretreatment of the cells with the clinically available antioxidant N-acetyl cysteine (NAC, 5 mM for 30 min inhibited these changes during subsequent application of cocaine and mitigated cocaine-induced toxicity. Despite repeated cocaine exposure, NAC pretreated cells remained highly viable and post NAC treatment also increased viability of cocaine treated cells to a smaller yet significant level. We show further that this alleviation by NAC is mediated through an increase in GSH levels in the cells. These findings, coupled with the fact that astrocytes maintain neuronal integrity, suggest that compounds which target and mitigate these early toxic changes in astrocytes could have a potentially broad therapeutic role in cocaine-induced CNS damage.

  3. Acupuncture reduces relapse to cocaine-seeking behavior via activation of GABA neurons in the ventral tegmental area.

    Science.gov (United States)

    Jin, Wyju; Kim, Min Sun; Jang, Eun Young; Lee, Jun Yeon; Lee, Jin Gyeom; Kim, Hong Yu; Yoon, Seong Shoon; Lee, Bong Hyo; Chang, Suchan; Kim, Jae Hyo; Choi, Kwang H; Koo, Ho; Gwak, Young Seob; Steffensen, Scott C; Ryu, Yeon-Hee; Kim, Hee Young; Yang, Chae Ha

    2017-03-07

    There is growing public interest in alternative approaches to addiction treatment and scientific interest in elucidating the neurobiological underpinnings of acupuncture. Our previous studies showed that acupuncture at a specific Shenmen (HT7) points reduced dopamine (DA) release in the nucleus accumbens (NAc) induced by drugs of abuse. The present study was carried out to evaluate the effects of HT7 acupuncture on γ-aminobutyric acid (GABA) neuronal activity in the ventral tegmental area (VTA) and the reinstatement of cocaine-seeking behavior. Using microdialysis and in vivo single-unit electrophysiology, we evaluated the effects of HT7 acupuncture on VTA GABA and NAc DA release and VTA GABA neuronal activity in rats. Using a within-session reinstatement paradigm in rats self-administering cocaine, we evaluated the effects of HT7 stimulation on cocaine-primed reinstatement. Acupuncture at HT7 significantly reduced cocaine suppression of GABA release and GABA neuron firing rates in the VTA. HT7 acupuncture attenuated cocaine-primed reinstatement, which was blocked by VTA infusions of the selective GABAB receptor antagonist 2-hydroxysaclofen. HT7 stimulation significantly decreased acute cocaine-induced DA release in the NAc, which was also blocked by 2-hydroxysaclofen. HT7 acupuncture also attenuated cocaine-induced sensitization of extracellular DA levels in the NAc. Moreover, HT7 acupuncture reduced both locomotor activity and neuronal activation in the NAc induced by acute cocaine in a needle-penetration depth-dependent fashion. These results suggest that acupuncture may suppress cocaine-induced DA release in the NAc and cocaine-seeking behavior through activation of VTA GABA neurons. Acupuncture may be an effective therapy to reduce cocaine relapse by enhancing GABAergic inhibition in the VTA.

  4. Corticosterone regulates both naturally occurring and cocaine-induced dopamine signaling by selectively decreasing dopamine uptake.

    Science.gov (United States)

    Wheeler, Daniel S; Ebben, Amanda L; Kurtoglu, Beliz; Lovell, Marissa E; Bohn, Austin T; Jasek, Isabella A; Baker, David A; Mantsch, John R; Gasser, Paul J; Wheeler, Robert A

    2017-10-01

    Stressful and aversive events promote maladaptive reward-seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our lab and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine's effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast-scan cyclic voltammetry, we examined the effect of systemic corticosterone on spontaneous dopamine release events (transients) in the NAc core and shell in behaving rats. A physiologically relevant systemic injection of corticosterone (2 mg/kg i.p.) induced an increase in dopamine transient amplitude and duration (both voltammetric measures sensitive to decreases in dopamine clearance), but had no effect on the frequency of transient release events. This effect was compounded by cocaine (2.5 mg/kg i.p.). However, a second experiment indicated that the same injection of corticosterone had no detectable effect on the dopaminergic encoding of a palatable natural reward (saccharin). Taken together, these results suggest that corticosterone interferes with naturally-occurring dopamine uptake locally, and this effect is a critical determinant of dopamine concentration specifically in situations in which the dopamine transporter is pharmacologically blocked by cocaine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Sensitivity analysis of the fission gas behavior model in BISON.

    Energy Technology Data Exchange (ETDEWEB)

    Swiler, Laura Painton; Pastore, Giovanni; Perez, Danielle; Williamson, Richard

    2013-05-01

    This report summarizes the result of a NEAMS project focused on sensitivity analysis of a new model for the fission gas behavior (release and swelling) in the BISON fuel performance code of Idaho National Laboratory. Using the new model in BISON, the sensitivity of the calculated fission gas release and swelling to the involved parameters and the associated uncertainties is investigated. The study results in a quantitative assessment of the role of intrinsic uncertainties in the analysis of fission gas behavior in nuclear fuel.

  6. Mice lacking neuropeptide Y show increased sensitivity to cocaine

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Woldbye, David Paul Drucker

    2012-01-01

    There is increasing data implicating neuropeptide Y (NPY) in the neurobiology of addiction. This study explored the possible role of NPY in cocaine-induced behavior using NPY knockout mice. The transgenic mice showed a hypersensitive response to cocaine in three animal models of cocaine addiction...

  7. Cocaine induces cell death and activates the transcription nuclear factor kappa-b in pc12 cells

    Science.gov (United States)

    Lepsch, Lucilia B; Munhoz, Carolina D; Kawamoto, Elisa M; Yshii, Lidia M; Lima, Larissa S; Curi-Boaventura, Maria F; Salgado, Thais ML; Curi, Rui; Planeta, Cleopatra S; Scavone, Cristoforo

    2009-01-01

    Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several neurotransmitter systems. For example, cocaine increases extracellular levels of dopamine and free radicals, and modulates several transcription factors. NF-κB is a transcription factor that regulates gene expression involved in cellular death. Our aim was to investigate the toxicity and modulation of NF-κB activity by cocaine in PC 12 cells. Treatment with cocaine (1 mM) for 24 hours induced DNA fragmentation, cellular membrane rupture and reduction of mitochondrial activity. A decrease in Bcl-2 protein and mRNA levels, and an increase in caspase 3 activity and cleavage were also observed. In addition, cocaine (after 6 hours treatment) activated the p50/p65 subunit of NF-κB complex and the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, attenuated the NF-κB activation. Inhibition of NF-κB activity by using PDTC and Sodium Salicilate increased cell death caused by cocaine. These results suggest that cocaine induces cell death (apoptosis and necrosis) and activates NF-κB in PC12 cells. This activation occurs, at least partially, due to activation of D1 receptors and seems to have an anti-apoptotic effect on these cells. PMID:19183502

  8. Cocaine induces cell death and activates the transcription nuclear factor kappa-b in pc12 cells

    Directory of Open Access Journals (Sweden)

    Lepsch Lucilia B

    2009-02-01

    Full Text Available Abstract Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several neurotransmitter systems. For example, cocaine increases extracellular levels of dopamine and free radicals, and modulates several transcription factors. NF-κB is a transcription factor that regulates gene expression involved in cellular death. Our aim was to investigate the toxicity and modulation of NF-κB activity by cocaine in PC 12 cells. Treatment with cocaine (1 mM for 24 hours induced DNA fragmentation, cellular membrane rupture and reduction of mitochondrial activity. A decrease in Bcl-2 protein and mRNA levels, and an increase in caspase 3 activity and cleavage were also observed. In addition, cocaine (after 6 hours treatment activated the p50/p65 subunit of NF-κB complex and the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, attenuated the NF-κB activation. Inhibition of NF-κB activity by using PDTC and Sodium Salicilate increased cell death caused by cocaine. These results suggest that cocaine induces cell death (apoptosis and necrosis and activates NF-κB in PC12 cells. This activation occurs, at least partially, due to activation of D1 receptors and seems to have an anti-apoptotic effect on these cells.

  9. A single social defeat induces short-lasting behavioral sensitization to amphetamine

    NARCIS (Netherlands)

    de Jong, JG; Wasilewski, M; van der Vegt, BJ; Buwalda, B; Koolhaas, Jacob

    2005-01-01

    Repeated, intermittent exposure to psychostimulants or stressors results in long-lasting, progressive sensitization of the behavioral effects of a subsequent amphetamine (AMPH) challenge. Although behavioral sensitization has also been observed following a single drug pretreatment, the sensitizing p

  10. Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats

    OpenAIRE

    Vollbrecht, Peter J.; Nobile, Cameron W; Chadderdon, Aaron M.; Jutkiewicz, Emily M.; Ferrario, Carrie R

    2015-01-01

    Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility...

  11. Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats

    OpenAIRE

    Vollbrecht, Peter J.; Nobile, Cameron W.; Chadderdon, Aaron M.; Jutkiewicz, Emily M.; Ferrario, Carrie R.

    2015-01-01

    Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility...

  12. Behavioral sensitivity to broadband binaural localization cues in the ferret.

    Science.gov (United States)

    Keating, Peter; Nodal, Fernando R; Gananandan, Kohilan; Schulz, Andreas L; King, Andrew J

    2013-08-01

    Although the ferret has become an important model species for studying both fundamental and clinical aspects of spatial hearing, previous behavioral work has focused on studies of sound localization and spatial release from masking in the free field. This makes it difficult to tease apart the role played by different spatial cues. In humans and other species, interaural time differences (ITDs) and interaural level differences (ILDs) play a critical role in sound localization in the azimuthal plane and also facilitate sound source separation in noisy environments. In this study, we used a range of broadband noise stimuli presented via customized earphones to measure ITD and ILD sensitivity in the ferret. Our behavioral data show that ferrets are extremely sensitive to changes in either binaural cue, with levels of performance approximating that found in humans. The measured thresholds were relatively stable despite extensive and prolonged (>16 weeks) testing on ITD and ILD tasks with broadband stimuli. For both cues, sensitivity was reduced at shorter durations. In addition, subtle effects of changing the stimulus envelope were observed on ITD, but not ILD, thresholds. Sensitivity to these cues also differed in other ways. Whereas ILD sensitivity was unaffected by changes in average binaural level or interaural correlation, the same manipulations produced much larger effects on ITD sensitivity, with thresholds declining when either of these parameters was reduced. The binaural sensitivity measured in this study can largely account for the ability of ferrets to localize broadband stimuli in the azimuthal plane. Our results are also broadly consistent with data from humans and confirm the ferret as an excellent experimental model for studying spatial hearing.

  13. Sensitivity analysis techniques for models of human behavior.

    Energy Technology Data Exchange (ETDEWEB)

    Bier, Asmeret Brooke

    2010-09-01

    Human and social modeling has emerged as an important research area at Sandia National Laboratories due to its potential to improve national defense-related decision-making in the presence of uncertainty. To learn about which sensitivity analysis techniques are most suitable for models of human behavior, different promising methods were applied to an example model, tested, and compared. The example model simulates cognitive, behavioral, and social processes and interactions, and involves substantial nonlinearity, uncertainty, and variability. Results showed that some sensitivity analysis methods create similar results, and can thus be considered redundant. However, other methods, such as global methods that consider interactions between inputs, can generate insight not gained from traditional methods.

  14. Role of Matrix Metalloproteinases in the Acquisition and Reconsolidation of Cocaine-Induced Conditioned Place Preference

    Science.gov (United States)

    Brown, Travis E.; Forquer, Melissa R.; Cocking, Davelle L.; Jansen, Heiko T.; Harding, Joseph W.; Sorg, Barbara A.

    2007-01-01

    Persistent drug seeking/taking behavior involves the consolidation of memory. With each drug use, the memory may be reactivated and reconsolidated to maintain the original memory. During reactivation, the memory may become labile and susceptible to disruption; thus, molecules involved in plasticity should influence acquisition and/or…

  15. Role of Matrix Metalloproteinases in the Acquisition and Reconsolidation of Cocaine-Induced Conditioned Place Preference

    Science.gov (United States)

    Brown, Travis E.; Forquer, Melissa R.; Cocking, Davelle L.; Jansen, Heiko T.; Harding, Joseph W.; Sorg, Barbara A.

    2007-01-01

    Persistent drug seeking/taking behavior involves the consolidation of memory. With each drug use, the memory may be reactivated and reconsolidated to maintain the original memory. During reactivation, the memory may become labile and susceptible to disruption; thus, molecules involved in plasticity should influence acquisition and/or…

  16. Phototransistor Behavior Based on Dye-Sensitized Solar Cell

    CERN Document Server

    Wang, X Q; Wang, Y F; Zhou, W Q; Lu, Y M; Liu, Z Y

    2012-01-01

    In the present work, a light-controlled device cell is established based on the dye-sensitized solar cell using nanocrystalline TiO2 films. Voltage-current curves are characterized by three types of transport behaviors: linear increase, saturated plateau and breakdown-like increase, which are actually of the typical performances for a photo-gated transistor. Moreover, an asymmetric behavior is observed in the voltage-current loops, which is believed to arise from the difference in the effective photo-conducting areas. The photovoltaic voltage between the shared counter electrode and drain (VCE-D) is investigated as well, clarifying that the predominant dark process in source and the predominant photovoltaic process in drain are series connected, modifying the electric potential levels and thus resulting in the characteristic phototransistor behaviors.

  17. An in vitro model of human neocortical development using pluripotent stem cells: cocaine-induced cytoarchitectural alterations.

    Science.gov (United States)

    Kindberg, Abigail A; Bendriem, Raphael M; Spivak, Charles E; Chen, Jia; Handreck, Annelie; Lupica, Carl R; Liu, Jinny; Freed, William J; Lee, Chun-Ting

    2014-12-01

    Neocortical development involves ordered specification of forebrain cortical progenitors to various neuronal subtypes, ultimately forming the layered cortical structure. Modeling of this process using human pluripotent stem cells (hPSCs) would enable mechanistic studies of human neocortical development, while providing new avenues for exploration of developmental neocortical abnormalities. Here, we show that preserving hPSCs aggregates - allowing embryoid body formation - while adding basic fibroblast growth factor (bFGF) during neuroepithelial development generates neural rosettes showing dorsal forebrain identity, including Mash1(+) dorsal telencephalic GABAergic progenitors. Structures that mirrored the organization of the cerebral cortex formed after rosettes were seeded and cultured for 3 weeks in the presence of FGF18, BDNF and NT3. Neurons migrated along radial glia scaffolding, with deep-layer CTIP2(+) cortical neurons appearing after 1 week and upper-layer SATB2(+) cortical neurons forming during the second and third weeks. At the end of differentiation, these structures contained both glutamatergic and GABAergic neurons, with glutamatergic neurons being most abundant. Thus, this differentiation protocol generated an hPSC-based model that exhibits temporal patterning and a neuronal subtype ratio similar to that of the developing human neocortex. This model was used to examine the effects of cocaine during neocorticogenesis. Cocaine caused premature neuronal differentiation and enhanced neurogenesis of various cortical neuronal subtypes. These cocaine-induced changes were inhibited by the cytochrome P450 inhibitor cimetidine. This in vitro model enables mechanistic studies of neocorticogenesis, and can be used to examine the mechanisms through which cocaine alters the development of the human neocortex.

  18. Cocaine-induced changes of synaptic transmission in the striatum are modulated by adenosine A2A receptors and involve the tyrosine phosphatase STEP.

    Science.gov (United States)

    Chiodi, Valentina; Mallozzi, Cinzia; Ferrante, Antonella; Chen, Jiang F; Lombroso, Paul J; Di Stasi, Anna Maria Michela; Popoli, Patrizia; Domenici, Maria Rosaria

    2014-02-01

    The striatum is a brain area implicated in the pharmacological action of drugs of abuse. Adenosine A2A receptors (A2ARs) are highly expressed in the striatum and mediate, at least in part, cocaine-induced psychomotor effects in vivo. Here we studied the synaptic mechanisms implicated in the pharmacological action of cocaine in the striatum and investigated the influence of A2ARs. We found that synaptic transmission was depressed in corticostriatal slices after perfusion with cocaine (10 μM). This effect was reduced by the A2AR antagonist ZM241385 and almost abolished in striatal A2AR-knockout mice (mice lacking A2ARs in striatal neurons, stA2ARKO). The effect of cocaine on synaptic transmission was also prevented by the protein tyrosine phosphatases (PTPs) inhibitor sodium orthovanadate (Na3VO4). In synaptosomes prepared from striatal slices, we found that the activity of striatal-enriched protein tyrosine phosphatase (STEP) was upregulated by cocaine, prevented by ZM241385, and absent in synaptosomes from stA2ARKO. The role played by STEP in cocaine modulation of synaptic transmission was investigated in whole-cell voltage clamp recordings from medium spiny neurons of the striatum. We found that TAT-STEP, a peptide that renders STEP enzymatically inactive, prevented cocaine-induced reduction in AMPA- and NMDA-mediated excitatory post-synaptic currents, whereas the control peptide, TAT-myc, had no effect. These results demonstrate that striatal A2ARs modulate cocaine-induced synaptic depression in the striatum and highlight the potential role of PTPs and specifically STEP in the effects of cocaine.

  19. Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes.

    Directory of Open Access Journals (Sweden)

    Amber N Brown

    Full Text Available Drugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y exposed to nicotine or cocaine. Widespread, drug- and time-resolved repositioning of nucleosomes was identified at the transcription start site and promoter region of multiple genes. Nicotine and cocaine produced unique and shared changes in terms of the numbers and types of genes affected, as well as repositioning of nucleosomes at sites which could increase or decrease the probability of gene expression based on DNA accessibility. Half of the drug-induced nucleosome positions approximated a theoretical model of nucleosome occupancy based on physical and chemical characteristics of the DNA sequence, whereas the basal or drug naïve positions were generally DNA sequence independent. Thus we suggest that nucleosome repositioning represents an initial dynamic genome-wide alteration of the transcriptional landscape preceding more selective downstream transcriptional reprogramming, which ultimately characterizes the cell- and tissue-specific responses to drugs of abuse.

  20. Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes.

    Science.gov (United States)

    Brown, Amber N; Vied, Cynthia; Dennis, Jonathan H; Bhide, Pradeep G

    2015-01-01

    Drugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y) exposed to nicotine or cocaine. Widespread, drug- and time-resolved repositioning of nucleosomes was identified at the transcription start site and promoter region of multiple genes. Nicotine and cocaine produced unique and shared changes in terms of the numbers and types of genes affected, as well as repositioning of nucleosomes at sites which could increase or decrease the probability of gene expression based on DNA accessibility. Half of the drug-induced nucleosome positions approximated a theoretical model of nucleosome occupancy based on physical and chemical characteristics of the DNA sequence, whereas the basal or drug naïve positions were generally DNA sequence independent. Thus we suggest that nucleosome repositioning represents an initial dynamic genome-wide alteration of the transcriptional landscape preceding more selective downstream transcriptional reprogramming, which ultimately characterizes the cell- and tissue-specific responses to drugs of abuse.

  1. Topiramate's effects on cocaine-induced subjective mood, craving and preference for money over drug taking.

    Science.gov (United States)

    Johnson, Bankole A; Roache, John D; Ait-Daoud, Nassima; Gunderson, Erik W; Haughey, Heather M; Wang, Xin-Qun; Liu, Lei

    2013-05-01

    Topiramate, presumably through antagonism of excitatory glutaminergic pathways and facilitation of inhibitory gamma-aminobutyric acid neurons in the cortico-mesolimbic system, might reduce cocaine's abuse liability. We tested whether topiramate (100 mg twice daily) would reduce the euphoria, subjective mood, craving and preference for cocaine over money induced by low and high doses (0.325 and 0.65 mg/kg i.v., respectively) of experimentally administered cocaine in 24 male and female, cocaine-dependent, non-treatment-seeking research volunteers in a university in-patient laboratory. We utilized a randomized, double-blind, placebo-controlled, within-subject, Latin-square cross-over design in which three experimental challenge doses of low-dose cocaine, high-dose cocaine and placebo were administered in counterbalanced order after 5 days of topiramate or matching placebo pre-treatments separated by a 1-week washout period (2006-2009). After placebo pre-treatments, cocaine produced dose-related increases in euphoria, stimulant effects, craving for more cocaine and monetary value of cocaine in a behavioral preference test of cocaine versus money choice. Topiramate pre-treatment reduced the cocaine-related craving and monetary value of high-dose cocaine while increasing the monetary value, euphoria and stimulant effects of low-dose cocaine. Validated and standardized human experimental methods evaluating the potential for topiramate to alter cocaine's abuse liability suggest that topiramate may reduce the reinforcing effects and craving induced by higher cocaine doses. Low-dose cocaine might appear to have some enhancement of its stimulant properties in the presence of topiramate's prominent sedative effects. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

  2. A computational model that predicts behavioral sensitivity to intracortical microstimulation

    Science.gov (United States)

    Kim, Sungshin; Callier, Thierri; Bensmaia, Sliman J.

    2017-02-01

    Objective. Intracortical microstimulation (ICMS) is a powerful tool to investigate the neural mechanisms of perception and can be used to restore sensation for patients who have lost it. While sensitivity to ICMS has previously been characterized, no systematic framework has been developed to summarize the detectability of individual ICMS pulse trains or the discriminability of pairs of pulse trains. Approach. We develop a simple simulation that describes the responses of a population of neurons to a train of electrical pulses delivered through a microelectrode. We then perform an ideal observer analysis on the simulated population responses to predict the behavioral performance of non-human primates in ICMS detection and discrimination tasks. Main results. Our computational model can predict behavioral performance across a wide range of stimulation conditions with high accuracy (R 2 = 0.97) and generalizes to novel ICMS pulse trains that were not used to fit its parameters. Furthermore, the model provides a theoretical basis for the finding that amplitude discrimination based on ICMS violates Weber’s law. Significance. The model can be used to characterize the sensitivity to ICMS across the range of perceptible and safe stimulation regimes. As such, it will be a useful tool for both neuroscience and neuroprosthetics.

  3. Endogenous cholinergic neurotransmission contributes to behavioral sensitization to morphine.

    Directory of Open Access Journals (Sweden)

    Dusica Bajic

    Full Text Available Neuroplasticity in the mesolimbic dopaminergic system is critical for behavioral adaptations associated with opioid reward and addiction. These processes may be influenced by cholinergic transmission arising from the laterodorsal tegmental nucleus (LDTg, a main source of acetylcholine to mesolimbic dopaminergic neurons. To examine this possibility we asked if chronic systemic morphine administration affects expression of genes in ventral and ventrolateral periaqueductal gray at the level of the LDTg using rtPCR. Specifically, we examined gene expression changes in the area of interest using Neurotransmitters and Receptors PCR array between chronic morphine and saline control groups. Analysis suggested that chronic morphine administration led to changes in expression of genes associated, in part, with cholinergic neurotransmission. Furthermore, using a quantitative immunofluorescent technique, we found that chronic morphine treatment produced a significant increase in immunolabeling of the cholinergic marker (vesicular acetylcholine transporter in neurons of the LDTg. Finally, systemic administration of the nonselective and noncompetitive neuronal nicotinic antagonist mecamylamine (0.5 or 2 mg/kg dose-dependently blocked the expression, and to a lesser extent the development, of locomotor sensitization. The same treatment had no effect on acute morphine antinociception, antinociceptive tolerance or dependence to chronic morphine. Taken together, the results suggest that endogenous nicotinic cholinergic neurotransmission selectively contributes to behavioral sensitization to morphine and this process may, in part, involve cholinergic neurons within the LDTg.

  4. AAVrh.10-Mediated Expression of an Anti-Cocaine Antibody Mediates Persistent Passive Immunization That Suppresses Cocaine-Induced Behavior

    Science.gov (United States)

    Rosenberg, Jonathan B.; Hicks, Martin J.; De, Bishnu P.; Pagovich, Odelya; Frenk, Esther; Janda, Kim D.; Wee, Sunmee; Koob, George F.; Hackett, Neil R.; Kaminsky, Stephen M.; Worgall, Stefan; Tignor, Nicole; Mezey, Jason G.

    2012-01-01

    Abstract Cocaine addiction is a major problem affecting all societal and economic classes for which there is no effective therapy. We hypothesized an effective anti-cocaine vaccine could be developed by using an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain. To accomplish this, we constructed AAVrh.10antiCoc.Mab, an AAVrh.10 gene transfer vector expressing the heavy and light chains of the high affinity anti-cocaine monoclonal antibody GNC92H2. Intravenous administration of AAVrh.10antiCoc.Mab to mice mediated high, persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood. With repeated intravenous cocaine challenge, naive mice exhibited hyperactivity, while the AAVrh.10antiCoc.Mab-vaccinated mice were completely resistant to the cocaine. These observations demonstrate a novel strategy for cocaine addiction by requiring only a single administration of an AAV vector mediating persistent, systemic anti-cocaine passive immunity. PMID:22486244

  5. Cocaine induces nuclear export and degradation of neuronal retinoid X receptor-γ via a TNF-α/JNK- mediated mechanism.

    Science.gov (United States)

    Kovalevich, Jane; Yen, William; Ozdemir, Ahmet; Langford, Dianne

    2015-03-01

    Cocaine abuse represents an immense societal health and economic burden for which no effective treatment currently exists. Among the numerous intracellular signaling cascades impacted by exposure to cocaine, increased and aberrant production of pro-inflammatory cytokines in the CNS has been observed. Additionally, we have previously reported a decrease in retinoid-X-receptor-gamma (RXR-γ) in brains of mice chronically exposed to cocaine. Through obligate heterodimerization with a number of nuclear receptors, RXRs serve as master regulatory transcription factors, which can potentiate or suppress expression of a wide spectrum of genes. Little is known about the regulation of RXR levels, but previous studies indicate cellular stressors such as cytokines negatively regulate levels of RXRs in vitro. To evaluate the mechanism underlying the cocaine-induced decreases in RXR-γ levels observed in vivo, we exposed neurons to cocaine in vitro and examined pathways which may contribute to disruption in RXR signaling, including activation of stress pathways by cytokine induction. In these studies, we provide the first evidence that cocaine exposure disrupts neuronal RXR-γ signaling in vitro by promoting its nuclear export and degradation. Furthermore, we demonstrate this effect may be mediated, at least in part, by cocaine-induced production of TNF-α and its downstream effector c-Jun-NH-terminal kinase (JNK). Findings from this study are therefore applicable to both cocaine abuse and to pathological conditions characterized by neuroinflammatory factors, such as neurodegenerative disease.

  6. Cannabidiol, a Cannabis sativa constituent, inhibits cocaine-induced seizures in mice: Possible role of the mTOR pathway and reduction in glutamate release.

    Science.gov (United States)

    Gobira, Pedro H; Vilela, Luciano R; Gonçalves, Bruno D C; Santos, Rebeca P M; de Oliveira, Antonio C; Vieira, Luciene B; Aguiar, Daniele C; Crippa, José A; Moreira, Fabricio A

    2015-09-01

    Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders. Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties. Its effects against cocaine neurotoxicity, however, have remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms. CBD (30 mg/kg) pre-treatment increased the latency and reduced the duration of cocaine (75 mg/kg)-induced seizures in mice. The CB1 receptor antagonist, AM251 (1 and 3mg/kg), and the CB2 receptor antagonist, AM630 (2 and 4 mg/kg), failed to reverse this protective effect, suggesting that alternative mechanisms are involved. Synaptosome studies with the hippocampus of drug-treated animals revealed that cocaine increases glutamate release, whereas CBD induces the opposite effect. Finally, the protective effect of this cannabinoid against cocaine-induced seizure was reversed by rapamycin (1 and 5mg/kg), an inhibitor of the mammalian target of rapamycin (mTOR) intracellular pathway. In conclusion, CBD protects against seizures in a model of cocaine intoxication. These effects possibly occur through activation of mTOR with subsequent reduction in glutamate release. CBD should be further investigated as a strategy for alleviating psychostimulant toxicity.

  7. Detonation behavior of emulsion explosives sensitized with polymeric microballoons

    Science.gov (United States)

    Mendes, Ricardo; Ribeiro, José; Plaksin, Igor; Campos, José

    2013-06-01

    The differences between the detonation behavior of ammonium nitrate based emulsion explosive sensitized with polymeric or with glass microballoons is presented and discussed. Expancel® are hollow polymeric microballoons that contain a hydrocarbon gas. The mean particle size of those particles is 30 μm and their wall thickness is about 0.1 μm. The detonation velocity and the failure diameter of the emulsion explosive sensitized with different amounts of these particles were measured, in cylindrical charges, by ionization pins and optical fibers. The detonation velocity of emulsion explosives shows a non-monotonic evolution with the density with the maximum being reached far below the maximum density. The detonation fails when the density approaches the one of the matrix. The failure diameter increases with increasing density. For low densities the detonation velocity is almost independent of the charge diameter and it is close to the values predict by BKW EoS. The effect of the nature and size of the microballoons on the detonation front curvature and failure diameter was also determined.

  8. Huperzine A inhibits immediate addictive behavior but not behavioral sensitization following repeated morphine administration in rats.

    Science.gov (United States)

    Sun, Jinling; Tian, Lin; Cui, Ruisi; Li, Xinwang

    2017-04-01

    Acetylcholinesterase inhibitors are regarded as promising therapeutic agents to treat addiction. The current study aimed to examine the effects of huperzine A, a cholinesterase inhibitor, on behavioral sensitization induced by repeated morphine administration and relapse induced by contextual conditioning. The present study also assessed whether the state-dependency hypothesis may explain the results. Adult rats were divided into four groups (n=8) and intraperitoneally injected with 0.2, 0.3 or 0.4 mg/kg huperzine A or saline (1 ml/kg, control), for 5 days. The effect of repeated huperzine A administration alone on locomotor activity was assessed. For the experiments that analyzed the development of morphine-induced sensitization, 40 rats were divided into five groups (n=8): Saline+Saline, Saline+Morphine, 0.2, 0.3 and 0.4 mg/kg huperzine A+Morphine. Following a withdrawal period of 7 days, all animals were administered saline or morphine, as appropriate. To test the state-dependency hypothesis, the rats in the Saline+Morphine group were injected with saline and morphine, while the other three groups were administered different doses of huperzine A and morphine. To examine the effect of huperzine A on the expression of morphine-induced sensitization, the rats in huperzine A+Morphine groups were injected with appropriate concentrations of huperzine A, and morphine. The current results indicated that the administration of huperzine A alone did not affect locomotor activity, while higher doses of huperzine A inhibited the addictive behavior induced by morphine at the development phase. Additionally, huperzine A administration during the expression phase of morphine sensitization did not inhibit the relapse induced by administration of saline. Furthermore, 0.4 mg/kg huperzine A inhibited the expression of morphine-induced behavioral sensitization. Therefore, the results of the current study do not support the state-dependency hypothesis.

  9. A sensitive period for environmental regulation of eating behavior and leptin sensitivity.

    Science.gov (United States)

    Mainardi, Marco; Scabia, Gaia; Vottari, Teresa; Santini, Ferruccio; Pinchera, Aldo; Maffei, Lamberto; Pizzorusso, Tommaso; Maffei, Margherita

    2010-09-21

    Western lifestyle contributes to body weight dysregulation. Leptin down-regulates food intake by modulating the activity of neural circuits in the hypothalamic arcuate nucleus (ARC), and resistance to this hormone constitutes a permissive condition for obesity. Physical exercise modulates leptin sensitivity in diet-induced obese rats. The role of other lifestyle components in modulating leptin sensitivity remains elusive. Environmentally enriched mice were used to explore the effects of lifestyle change on leptin production/action and other metabolic parameters. We analyzed adult mice exposed to environmental enrichment (EE), which showed decreased leptin, reduced adipose mass, and increased food intake. We also analyzed 50-d-old mice exposed to either EE (YEE) or physical exercise (YW) since birth, both of which showed decreased leptin. YEE mice showed no change in food intake, increased response to leptin administration, increased activation of STAT3 in the ARC. The YW leptin-induced food intake response was intermediate between young mice kept in standard conditions and YEE. YEE exhibited increased and decreased ratios of excitatory/inhibitory synapses onto α-melanocyte-stimulating hormone and agouti-related peptide neurons of the ARC, respectively. We also analyzed animals as described for YEE and then placed in standard cages for 1 mo. They showed no altered leptin production/action but demonstrated changes in excitatory/inhibitory synaptic contacts in the ARC similar to YEE. EE and physical activity resulted in improved insulin sensitivity. In conclusion, EE and physical activity had an impact on feeding behavior, leptin production/action, and insulin sensitivity, and EE affected ARC circuitry. The leptin-hypothalamic axis is maximally enhanced if environmental stimulation is applied during development.

  10. Characteristics of ethanol-induced behavioral sensitization in rats: Molecular mediators and cross-sensitization between ethanol and cocaine.

    Science.gov (United States)

    Xu, Shijie; Kang, Ung Gu

    2017-09-01

    Repeated exposure to drugs of abuse can induce a progressive increase in locomotor activity, known as behavioral sensitization. However, little is known about behavioral sensitization to ethanol. We examined whether ethanol could induce behavioral sensitization and investigated several molecular changes accompanying sensitization. We also assessed whether "cross-sensitization" occurred between ethanol and cocaine, another abused drug. Ethanol-induced sensitization was examined in rats after ethanol treatment (0.5 or 2g/kg) for 15days. The biochemical effects of low- or high-dose ethanol were examined in terms of N-methyl-d-aspartate (NMDA) receptor subunit phosphorylation or expression. Neuronal activity after ethanol treatment was assessed by measuring the level of early growth response (Egr-1) expression. Ethanol-induced behavioral sensitization was observed at the low dose (0.5g/kg) but not the high dose (2g/kg). Although acute treatment with the sensitizing dose of ethanol robustly increased Egr-1 protein and mRNA levels, the expression and phosphorylation of NMDA receptor subunits were not affected. The biochemical responses to ethanol seemed to be enhanced in ethanol-sensitized animals. Cross-sensitization between ethanol and cocaine was observed, which supports the hypothesis that there are commonalities among substances in the pathophysiology of substance dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 18-Methoxycoronaridine acts in the medial habenula to attenuate behavioral and neurochemical sensitization to nicotine.

    Science.gov (United States)

    Eggan, Branden L; McCallum, Sarah E

    2016-07-01

    Systemic 18-methoxycoronaridine, an alpha3beta4 nicotinic antagonist, slows the rate of induction of behavioral sensitization to nicotine (Glick et al., 1996; 2011). The primary mechanism of action of 18-MC is believed to be the inhibition of α3β4 nicotinic acetylcholine receptors which are densely expressed in the medial habenula and interpeduncular nucleus (Pace et al., 2004; Glick et al., 2012). Recently, these habenular nicotinic receptors and their multiple roles in nicotine aversion and withdrawal have been increasingly emphasized (Antolin-Fontes et al., 2015). Here, we investigated the effects of 18-MC on both behavioral and neurochemical sensitization to nicotine. Daily systemic administration of 18-MC slowed the rate of induction of behavioral sensitization to nicotine but failed to block the expression of a sensitized locomotor response when absent. In contrast, in nicotine sensitized animals, systemic 18-MC significantly reduced the expression of behavioral sensitization. Results from intra-habenular administration of 18-MC paralleled these findings in that the expression of behavioral sensitization was also reduced in sensitized animals. Consistent with its effects on behavioral sensitization, intra-MHb treatment with 18-MC completely abolished sensitized dopamine responses in the nucleus accumbens in nicotine sensitized animals. These results show that α3β4 nicotinic receptors in the MHb contribute to nicotine sensitization, a phenomenon associated with drug craving and relapse.

  12. Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

    Directory of Open Access Journals (Sweden)

    C.C. Justo

    2010-07-01

    Full Text Available Several lines of evidence indicate that the use of stimulant drugs, including methylphenidate (MPD, increases tobacco smoking. This has raised concerns that MPD use during adolescence could facilitate nicotine abuse. Preclinical studies have shown that repeated treatment with an addictive drug produces sensitization to that drug and usually cross-sensitization to other drugs. Behavioral sensitization has been implicated in the development of drug addiction. We examined whether repeated oral MPD administration during adolescence could induce behavioral sensitization to MPD and long-lasting cross-sensitization to nicotine. Adolescent male Wistar rats were treated orally with 10 mg/kg MPD or saline (SAL from postnatal day (PND 27 to 33. To evaluate behavioral sensitization to MPD in adolescent rats (PND 39, the SAL pretreated group was subdivided into two groups that received intragastric SAL (1.0 mL/kg or MPD (10 mg/kg; MPD pretreated rats received MPD (10 mg/kg. Cross-sensitization was evaluated on PND 39 or PND 70 (adulthood. To this end, SAL- and MPD-pretreated groups received subcutaneous injections of SAL (1.0 mL/kg or nicotine (0.4 mg/kg. All groups had 8 animals. Immediately after injections, locomotor activity was determined. The locomotor response to MPD challenge of MPD-pretreated rats was not significantly different from that of the SAL-pretreated group. Moreover, the locomotor response of MPD-pretreated rats to nicotine challenge was not significantly different from that of the SAL-pretreated group. This lack of sensitization and cross-sensitization suggests that MPD treatment during adolescence does not induce short- or long-term neuroadaptation in rats that could increase sensitivity to MPD or nicotine.

  13. Longitudinal Changes in Behavioral Approach System Sensitivity and Brain Structures Involved in Reward Processing during Adolescence

    Science.gov (United States)

    Urosevic, Snezana; Collins, Paul; Muetzel, Ryan; Lim, Kelvin; Luciana, Monica

    2012-01-01

    Adolescence is a period of radical normative changes and increased risk for substance use, mood disorders, and physical injury. Researchers have proposed that increases in reward sensitivity (i.e., sensitivity of the behavioral approach system [BAS]) and/or increases in reactivity to all emotional stimuli (i.e., reward and threat sensitivities)…

  14. Hypervigilance to Rejecting Stimuli in Rejection Sensitive Individuals: Behavioral and Neurocognitive Evidence.

    Science.gov (United States)

    Ehrlich, Katherine B; Gerson, Sarah A; Vanderwert, Ross E; Cannon, Erin N; Fox, Nathan A

    2015-10-01

    Individuals who are high in rejection sensitivity are vigilant toward social cues that signal rejection, and they exhibit attention biases towards information that confirms expectations of rejection. Little is known, however, about the neural correlates of rejection sensitivity. The present study examined whether rejection sensitivity is associated with individuals' neural responses to rejection-relevant information. Female participants, classified as high or average in rejection sensitivity, completed a modified dot-probe task in which a neutral face was paired with either another neutral face or a gaze-averted ("rejecting") face while EEG was collected and ERP components were computed. Behavioral results indicated that average rejection sensitive participants showed an attention bias away from rejecting faces, while high rejection sensitive participants were equally vigilant to neutral and rejecting faces. High rejection sensitivity was associated with ERP components signaling elevated attention and arousal to faces. These findings suggest that rejection sensitivity shapes behavioral and neurocognitive responses to faces.

  15. Quinine enhances the behavioral stimulant effect of cocaine in mice.

    Science.gov (United States)

    Huertas, Adriana; Wessinger, William D; Kucheryavykh, Yuri V; Sanabria, Priscila; Eaton, Misty J; Skatchkov, Serguei N; Rojas, Legier V; Maldonado-Martínez, Gerónimo; Inyushin, Mikhail Y

    2015-02-01

    The Na(+)-dependent dopamine transporter (DAT) is primarily responsible for regulating free dopamine (DA) concentrations in the brain by participating in the majority of DA uptake; however, other DA transporters may also participate, especially if cocaine or other drugs of abuse compromise DAT. Recently, such cocaine-insensitive low-affinity mono- and poly-amine OCT transporters were described in astrocytes which use DA as a substrate. These transporters are from a different transporter family and while insensitive to cocaine, they are specifically blocked by quinine and some steroids. Quinine is inexpensive and is often found in injected street drugs as an "adulterant". The present study was designed to determine the participation of OCTs in cocaine dependent behavioral and physiological changes in mice. Using FVB mice we showed, that daily single injections of quinine (10 mg/kg, i.p.) co-administered with cocaine (15 mg/kg, i.p.) for 10 days significantly enhanced cocaine-induced locomotor behavioral sensitization. Quinine had no significant effect on the time course of behavioral activation. In astrocytes from the ventral tegmental area of mice, transporter currents of quinine-sensitive monoamine transporters were also augmented after two weeks of cocaine administration. The importance of low-affinity high-capacity transporters for DA clearance is discussed, explaining the known ability of systemically administered DAT inhibitors to anomalously increase DA clearance.

  16. THE PHOTORESPONSE BEHAVIOR OF A MEH-PPV SENSITIZED ...

    African Journals Online (AJOL)

    Photovoltaic cells based on composite films of nc-TiO2 and ... we have designed a solid-state polymer-sensitized nc-TiO2 PEC where MEH-PPV was used as a ..... Gebeyehu, D.; Brabec, C.J.; Sariciftci, N.S. Thin Solid Films 2002, 271, 403. 16.

  17. Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish

    Directory of Open Access Journals (Sweden)

    Eric J. Mersereau

    2016-05-01

    Full Text Available A sizeable portion of the societal drain from cocaine abuse results from the complications of in utero drug exposure. Because of challenges in using humans and mammalian model organisms as test subjects, much debate remains about the impact of in utero cocaine exposure. Zebrafish offer a number of advantages as a model in longitudinal toxicology studies and are quite sensitive physiologically and behaviorally to cocaine. In this study, we have used zebrafish to model the effects of embryonic pre-exposure to cocaine on development and on subsequent cardiovascular physiology and cocaine-induced conditioned place preference (CPP in longitudinal adults. Larval fish showed a progressive decrease in telencephalic size with increased doses of cocaine. These treated larvae also showed a dose dependent response in heart rate that persisted 24 h after drug cessation. Embryonic cocaine exposure had little effect on overall health of longitudinal adults, but subtle changes in cardiovascular physiology were seen including decreased sensitivity to isoproterenol and increased sensitivity to cocaine. These longitudinal adult fish also showed an embryonic dose-dependent change in CPP behavior, suggesting an increased sensitivity. These studies clearly show that pre-exposure during embryonic development affects subsequent cocaine sensitivity in longitudinal adults.

  18. Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish.

    Science.gov (United States)

    Mersereau, Eric J; Boyle, Cody A; Poitra, Shelby; Espinoza, Ana; Seiler, Joclyn; Longie, Robert; Delvo, Lisa; Szarkowski, Megan; Maliske, Joshua; Chalmers, Sarah; Darland, Diane C; Darland, Tristan

    2016-05-31

    A sizeable portion of the societal drain from cocaine abuse results from the complications of in utero drug exposure. Because of challenges in using humans and mammalian model organisms as test subjects, much debate remains about the impact of in utero cocaine exposure. Zebrafish offer a number of advantages as a model in longitudinal toxicology studies and are quite sensitive physiologically and behaviorally to cocaine. In this study, we have used zebrafish to model the effects of embryonic pre-exposure to cocaine on development and on subsequent cardiovascular physiology and cocaine-induced conditioned place preference (CPP) in longitudinal adults. Larval fish showed a progressive decrease in telencephalic size with increased doses of cocaine. These treated larvae also showed a dose dependent response in heart rate that persisted 24 h after drug cessation. Embryonic cocaine exposure had little effect on overall health of longitudinal adults, but subtle changes in cardiovascular physiology were seen including decreased sensitivity to isoproterenol and increased sensitivity to cocaine. These longitudinal adult fish also showed an embryonic dose-dependent change in CPP behavior, suggesting an increased sensitivity. These studies clearly show that pre-exposure during embryonic development affects subsequent cocaine sensitivity in longitudinal adults.

  19. Maternal separation altered behavior and neuronal spine density without influencing amphetamine sensitization.

    Science.gov (United States)

    Muhammad, Arif; Kolb, Bryan

    2011-09-30

    We studied the long-term influence of maternal separation (MS) on periadolescent behavior, adult amphetamine (AMPH) sensitization, and structural plasticity in the corticolimbic regions in rats. Male and female pups, separated daily for 3h from the dam during postnatal day 3-21, were tested for periadolescent exploratory, emotional, cognitive, and social behaviors. The development and persistence of drug-induced behavioral sensitization were tested by repeated AMPH administration and a challenge, respectively. The spine density was examined in the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the orbital frontal cortex (OFC) from Golgi-Cox stained neurons. The results showed that MS enhanced anxiety-like behavior in males. MS abolished the sex difference in playful attacks observed in controls with resultant feminization of male play behavior. Furthermore, the probability of complete rotation defense to face an attack was decreased in females. AMPH administration resulted in the development of behavioral sensitization that persisted at least for two weeks. Sensitization was not influenced by MS. MS increased the spine density in the NAc, the mPFC, and the OFC. Repeated AMPH administration increased the spine density in the NAc and the mPFC, and decreased it in the OFC. MS blocked the drug-induced alteration in these regions. In sum, MS during development influenced periadolescent behavior in males, and structurally reorganized cortical and subcortical brain regions without affecting AMPH-induced behavioral sensitization.

  20. Adolescent mice are more vulnerable than adults to single injection-induced behavioral sensitization to amphetamine

    OpenAIRE

    Kameda, Sonia Regina; Fukushiro, Daniela Fukue [UNIFESP; Trombin, Thaís Fernanda [UNIFESP; Procopio-Souza, Roberta [UNIFESP; Patti, Camilla de Lima [UNIFESP; Hollais, André Willian [UNIFESP; Calzavara, Mariana Bendlin [UNIFESP; Abílio, Vanessa Costhek [UNIFESP; Ribeiro, Rosana de Alencar [UNIFESP; Tufik, Sergio; D'Almeida, Vânia; Frussa Filho, Roberto [UNIFESP

    2011-01-01

    Drug-induced behavioral sensitization in rodents has enhanced our understanding of why drugs acquire increasing motivational and incentive value. Compared to adults, human adolescents have accelerated dependence courses with shorter times from first exposure to dependence. We compared adolescent and adult mice in their ability to develop behavioral sensitization to amphetamine following a single injection. Adult (90-day-old) and adolescent (45-day-old) male Swiss mice received an acute intrap...

  1. Women's finger sensitivity correlates with partnered sexual behavior but not solitary masturbation frequencies.

    Science.gov (United States)

    Brody, Stuart; Fischer, Agneta H; Hess, Ursula

    2008-01-01

    In a sample of 97 healthy Dutch female university students, women with greater finger tactile sensitivity (von Frey-type filaments) engaged more in partnered (but not solitary masturbation) sexual behavior. Orgasmic responses in the past 30 days were not correlated with finger sensitivity. Results are discussed in terms of differences between different sexual behaviors, as well as susceptibility to reinforcement, and psychoanalytic views of conversion hysteria.

  2. Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats

    Science.gov (United States)

    Eagle, Andrew L.; Singh, Robby; Kohler, Robert J.; Friedman, Amy L.; Liebowitz, Chelsea P.; Galloway, Matthew P.; Enman, Nicole M.; Jutkiewicz, Emily M.; Perrine, Shane A.

    2017-01-01

    Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague–Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0,10 or 20mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, asexpected. However, compared to control ratson Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. PMID:25712697

  3. How victim sensitivity leads to uncooperative behavior via expectancies of injustice

    Directory of Open Access Journals (Sweden)

    Simona eMaltese

    2016-01-01

    Full Text Available According to the Sensitivity-to-mean-intentions (SeMI model, dispositional victim sensitivity involves a suspicious mindset that is activated by situational cues and guides subsequent information processing and behavior like a schema. Study 1 tested whether victim-sensitive persons are more prone to form expectancies of injustice in ambiguous situations and whether these expectancies mediate the relationship between victim sensitivity and cooperation behavior in a trust game. Results show an indirect effect of victim sensitivity on cooperation after unfair treatment (vs control condition, mediated by expectancies of injustice. In Study 2 we directly manipulated the tendency to form expectancies of injustice in ambiguous situations to test for causality. Results confirmed that the readiness to expect unjust outcomes led to lower cooperation, compared to a control condition. These findings provide direct evidence that expectancy tendencies are implicated in elevated victim sensitivity and are of theoretical and practical relevance.

  4. Bystander Behavior in Bullying Situations: Basic Moral Sensitivity, Moral Disengagement and Defender Self-Efficacy

    Science.gov (United States)

    Thornberg, Robert; Jungert, Tomas

    2013-01-01

    The aim of the present study was to investigate how basic moral sensitivity in bullying, moral disengagement in bullying and defender self-efficacy were related to different bystander behaviors in bullying. Therefore, we examined pathways that linked students' basic moral sensitivity, moral disengagement, and defender self-efficacy to different…

  5. The efficacy of cognitive-behavioral interventions for reducing anxiety sensitivity: A meta-analytic review

    NARCIS (Netherlands)

    Smits, J.A.J.; Berry, A.C.; Tart, C.D.; Powers, M.B.

    2008-01-01

    The present study meta-analytically reviewed the efficacy of cognitive-behavioral therapy (CBT) vs. control conditions in the reduction of anxiety sensitivity. A computerized search was conducted to indentify CBT outcome studies that included the Anxiety Sensitivity Index as a dependent variable. Of

  6. Women's finger sensitivity correlates with partnered sexual behavior but not solitary masturbation frequencies

    NARCIS (Netherlands)

    Brody, S.; Fischer, A.H.; Hess, U.

    2008-01-01

    In a sample of 97 healthy Dutch female university students, women with greater finger tactile sensitivity (von Frey-type filaments) engaged more in partnered (but not solitary masturbation) sexual behavior. Orgasmic responses in the past 30 days were not correlated with finger sensitivity. Results a

  7. Women's finger sensitivity correlates with partnered sexual behavior but not solitary masturbation frequencies

    NARCIS (Netherlands)

    Brody, S.; Fischer, A.H.; Hess, U.

    2008-01-01

    In a sample of 97 healthy Dutch female university students, women with greater finger tactile sensitivity (von Frey-type filaments) engaged more in partnered (but not solitary masturbation) sexual behavior. Orgasmic responses in the past 30 days were not correlated with finger sensitivity. Results a

  8. Bystander Behavior in Bullying Situations: Basic Moral Sensitivity, Moral Disengagement and Defender Self-Efficacy

    Science.gov (United States)

    Thornberg, Robert; Jungert, Tomas

    2013-01-01

    The aim of the present study was to investigate how basic moral sensitivity in bullying, moral disengagement in bullying and defender self-efficacy were related to different bystander behaviors in bullying. Therefore, we examined pathways that linked students' basic moral sensitivity, moral disengagement, and defender self-efficacy to different…

  9. Adolescent behavioral and neural reward sensitivity : a test of the differential susceptibility theory

    NARCIS (Netherlands)

    Richards, J. S.; Vasquez, A. Arias; von Rhein, D.; van der Meer, D.; Franke, B.; Hoekstra, P. J.; Heslenfeld, D. J.; Oosterlaan, J.; Faraone, S. V.; Buitelaar, J. K.; Hartman, C. A.

    2016-01-01

    Little is known about the causes of individual differences in reward sensitivity. We investigated gene-environment interactions (GxE) on behavioral and neural measures of reward sensitivity, in light of the differential susceptibility theory. This theory states that individuals carrying plasticity g

  10. Sensitization of sexual behavior in ovariectomized rats by chronic estradiol treatment.

    Science.gov (United States)

    Jones, Sherri Lee; Farrell, Sara; Gregory, James Gardner; Pfaus, James G

    2013-06-01

    The ovariectomized (OVX) rat treated with estradiol benzoate (EB) is used to elucidate neuroendocrine mechanisms of sexual behavior. Chronic behavioral and pharmacological manipulations can be confounded by rising baselines, since females are behaviorally more sensitive to repeated EB injections. The literature lacks a systematic examination of chronic effects of EB administered alone to the sexually experienced OVX rat. Long-Evans rats were repeatedly treated (8 tests) with s.c. injections of 2, 5, or 10 μg EB at different time intervals (4 or 8 days). Female sexual behaviors as well as receipt of mounts, intromissions and ejaculations from the male were observed in the unilevel 4-hole pacing chamber. The effects of adrenalectomy (ADX) and strain (Long-Evans vs. Wistar) were also assessed. Long-Evans OVX rats treated with 5 μg EB every 8 days showed persistently low levels of sexual behavior. Sensitization was most robust following 10 μg EB at 4-day intervals. Very few sexual behaviors were ever induced by 2 μg EB. ADX did not affect the development of behavioral sensitization by 10μg EB. Therefore, to achieve a low steady state of sexual behaviors in sexually experienced Long-Evans OVX rats 5μg of EB administered every 8days is optimal, whereas a persistently high level of sexual behaviors is induced with 10 μg EB administered every 4 days. OVX Wistar rats are behaviorally more sensitive to EB. Behavioral sensitization to EB may serve as a mechanism to optimize reproductive success.

  11. The development of adolescents' internalizing behavior: longitudinal effects of maternal sensitivity and child inhibition.

    Science.gov (United States)

    van der Voort, Anja; Linting, Mariëlle; Juffer, Femmie; Bakermans-Kranenburg, Marian J; Schoenmaker, Christie; van Ijzendoorn, Marinus H

    2014-04-01

    Internalizing symptoms such as withdrawn and anxious-depressed behavior are common in adolescence. This prospective longitudinal study helps to gain insight into the development of internalizing behavior, focusing on the role of early parent-child interaction while ruling out genetic similarity as a confounder. More specifically, the central question addressed in this study was whether parental sensitivity and child inhibited temperament predict children's withdrawn and anxious-depressed behavior in middle childhood and adolescence. We followed 160 early-adopted children (53 % girls) from infancy to adolescence. Structural equation modeling was used to test relationships both prospectively and concurrently. The results revealed that more sensitive parenting in infancy and middle childhood predicted less inhibited behavior in adolescence, which in turn predicted fewer internalizing problems in adolescence. The findings suggest that maternal sensitivity lowers adolescents' inhibited behavior and decreases the risk for adolescents' internalizing problem behavior indirectly through lower levels of inhibition. Supporting sensitive parenting in the years before adolescence may protect children from developing inhibited behavior and internalizing behavior problems in adolescence.

  12. The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats

    Directory of Open Access Journals (Sweden)

    Colin N. Haile

    2012-11-01

    Full Text Available Medications that target norepinephrine (NE neurotransmission alter the behavioral effects of cocaine and may be beneficial for stimulant-use disorders. We showed previously that the short-acting, α1-adrenergic antagonist, prazosin, blocked drug-induced reinstatement of cocaine-seeking in rats and doxazosin (DOX, a longer-acting α1 antagonist blocked cocaine’s subjective effects in cocaine-dependent volunteers. To further characterize DOX as a possible pharmacotherapy for cocaine dependence, we assessed its impact on the development and expression of cocaine-induced locomotor sensitization in rats. Rats (n = 6–8 were administered saline, cocaine (COC, 10 mg/kg or DOX (0.3 or 1.0 mg/kg alone or in combination for 5 consecutive days (development. Following 10-days of drug withdrawal, all rats were administered COC and locomotor activity was again assessed (expression. COC increased locomotor activity across days indicative of sensitization. The high dose (1.0 mg/kg, but not the low dose (0.3 mg/kg of DOX significantly decreased the development and expression of COC sensitization. DOX alone did not differ from saline. These results are consistent with studies showing that α1 receptors are essential for the development and expression of cocaine’s behavioral effects. Results also suggest that blockade of both the development and expression of locomotor sensitization may be important characteristics of possible pharmacotherapies for cocaine dependence in humans.

  13. Chronic exposure to MDMA (Ecstasy elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants

    Directory of Open Access Journals (Sweden)

    Swann Alan C

    2006-01-01

    Full Text Available Abstract Background The recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA. Methods The objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg and a saline control group (N = 9/group. All three MDMA groups were treated for six consecutive days, followed by a 5-day washout, and subsequently re-challenged with their respective doses of MDMA (day 13. Rats were then given an additional 25-day washout period, and re-challenged (day 38 with similar MDMA doses as before followed by either 0.6 mg/kg amphetamine or 2.5 mg/kg methylphenidate on the next day (day 39. Open-field locomotor activity was recorded using a computerized automated activity monitoring system. Results Acute injection of 2.5 mg/kg MDMA showed no significant difference in locomotor activity from rats given saline (control group, while animals receiving acute 5.0 mg/kg or 10.0 mg/kg MDMA showed significant increases in locomotor activity. Rats treated chronically with 5.0 mg/kg and 10.0 mg/kg MDMA doses exhibited an augmented response, i.e., behavioral sensitization, on experimental day 13 in at least one locomotor index. On experimental day 38, all three MDMA groups demonstrated sensitization to MDMA in at least one locomotor index. Amphetamine and methylphenidate administration to MDMA-sensitized animals did not elicit any significant change

  14. A new buprenorphine analogy, thenorphine,inhibits morphine-induced behavioral sensitization in mice

    Institute of Scientific and Technical Information of China (English)

    Wen-liZHAO; Ze-huiGONG; Jian-huiLIANG

    2004-01-01

    AIM: To investigate effects of thenorphine, a new compound of partial agonist of μ-opioid receptor, on the locomotor activity and the behavioral sensitization to morphine in mice. METHODS: Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization. RESULTS: A single dose of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01). Co-administration of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the development,transfer, and expression of behavioral sensitization to morphine in mice (P<0.05 or P<0.01). CONCLUSION:Thenorphine inhibited morphine-induced behavioral sensitization in mice, suggesting that thenorphine may be effective against the addiction of opioids.

  15. A new buprenorphine analogy,thenorphine,inhibits morphine-induced behavioral sensitization in mice

    Institute of Scientific and Technical Information of China (English)

    Wen-li ZHAO; Ze-hui GONG; Jian-hui LIANG

    2004-01-01

    AIM: To investigate effects of thenorphine, a new compound of partial agonist of μ-opioid receptor, on the locomotor activity and the behavioral sensitization to morphine in mice. METHODS: Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization. RESULTS: A single dose of thenorphine (0.0625, 0.25, and 1.0mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01).Co-administration of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the development,transfer, and expression of behavioral sensitization to morphine in mice (P<0.05 or P<0.01). CONCLUSION:Thenorphine inhibited morphine-induced behavioral sensitization in mice, suggesting that thenorphine may be effective against the addiction of opioids.

  16. Neural and Behavioral Evidence for Infants' Sensitivity to the Trustworthiness of Faces.

    Science.gov (United States)

    Jessen, Sarah; Grossmann, Tobias

    2016-11-01

    Face evaluation is a key aspect of face processing in humans, serving important functions in regulating social interactions. Adults and preschool children readily evaluate faces with respect to a person's trustworthiness and dominance. However, it is unclear whether face evaluation is mainly a product of extensive learning or a foundational building block of face perception already during infancy. We examined infants' sensitivity to facial signs of trustworthiness (Experiment 1) and dominance (Experiment 2) by measuring ERPs and looking behavior in response to faces that varied with respect to the two facial attributes. Results revealed that 7-month-old infants are sensitive to facial signs of trustworthiness but not dominance. This sensitivity was reflected in infants' behavioral preference and in the modulation of brain responses previously linked to emotion detection from faces. These findings provide first evidence that processing faces with respect to trustworthiness has its origins in infancy and shed light on the behavioral and neural correlates of this early emerging sensitivity.

  17. Chronic cocaine-induced H3 acetylation and transcriptional activation of CaMKIIalpha in the nucleus accumbens is critical for motivation for drug reinforcement.

    Science.gov (United States)

    Wang, Lei; Lv, Zhigang; Hu, Zhaoyang; Sheng, Jian; Hui, Bin; Sun, Jie; Ma, Lan

    2010-03-01

    The regulation of gene expression in the brain reward regions is known to contribute to the pathogenesis and persistence of drug addiction. Increasing evidence suggests that the regulation of gene transcription is mediated by epigenetic mechanisms that alter the chromatin structure at specific gene promoters. To better understand the involvement of epigenetic regulation in drug reinforcement properties, rats were subjected to cocaine self-administration paradigm. Daily histone deacetylase (HDAC) inhibitor infusions in the shell of the nucleus accumbens (NAc) caused an upward shift in the dose-response curve under fixed-ratio schedule and increased the break point under progressive-ratio schedule, indicating enhanced motivation for self-administered drug. The effect of the HDAC inhibitor is attributed to the increased elevation of histone acetylation induced by chronic, but not acute, cocaine experience. In contrast, neutralizing the chronic cocaine-induced increase in histone modification by the bilateral overexpression of HDAC4 in the NAc shell reduced drug motivation. The association between the motivation for cocaine and the transcriptional activation of addiction-related genes by H3 acetylation in the NAc shell was analyzed. Among the genes activated by chronic cocaine experiences, the expression of CaMKIIalpha, but not CaMKIIbeta, correlated positively with motivation for the drug. Lentivirus-mediated shRNA knockdown experiments showed that CaMKIIalpha, but not CaMKIIbeta, in the NAc shell is essential for the maintenance of motivation to self-administered cocaine. These findings suggest that chronic drug-use-induced transcriptional activation of genes, such as CaMKIIalpha, modulated by H3 acetylation in the NAc is a critical regulatory mechanism underlying motivation for drug reinforcement.

  18. Protein expression profile in the striatum of rats with methamphetamine-induced behavioral sensitization.

    Science.gov (United States)

    Iwazaki, Takeshi; McGregor, Iain S; Matsumoto, Izuru

    2007-04-01

    Repeated administration of methamphetamine (MAP) results in an increased behavioral response to the drug during subsequent exposure. This phenomenon is called behavioral sensitization. Sensitization is an enduring phenomenon, and suggests chronic alterations in neuronal plasticity. MAP-induced sensitization has been proposed and widely investigated as an animal model of MAP psychosis and schizophrenia. However, little is known about the molecular mechanisms underlying MAP-induced sensitization. 2-DE-based proteomics allows us to examine global changes in protein expression in complex biological systems and to propose hypotheses concerning the mechanisms underlying various pathological conditions. In the present study, we examined protein expression profiles in the striatum of MAP-sensitized rats using 2-DE-based proteomics. Repeated administration of MAP (4.0 mg/kg, once a day, intraperitoneal (i.p.)) for 10 days significantly augmented the locomotor response to an MAP challenge injection (1.0 mg/kg, i.p.) on day 11. This enhanced activity was maintained even after a week of drug abstinence. 2-DE analysis revealed 42 protein spots were differentially regulated in the striatum of MAP-sensitized rats compared to control. Thirty-one protein spots were identified using MALDI-TOF, including synapsin II, synaptosomal-associated protein 25 (SNAP-25), adenylyl cyclase-associated protein 1 (CAP1), and dihydropyrimidinase-related protein 2 (DRP2). These proteins can be related to underlying mechanisms of MAP-induced behavioral sensitization, indicating cytoskeletal modification, and altered synaptic function.

  19. Differential effects of endomorphin-1 and -2 on amphetamine sensitization: neurochemical and behavioral aspects.

    Science.gov (United States)

    Chen, J C; Liang, K W; Huang, E Y

    2001-03-01

    Mu-opioid receptors are known to modulate mesolimbic dopaminergic activity in the ventral tegmental area via disinhibition of GABA-containing neurons. Recently, two novel tetrapeptides, endomorphin-1 and endomorphin-2, were identified in the mammalian brain and reported to have high binding affinities toward mu-opioid receptors. To determine if endomorphins would modulate the development of amphetamine sensitization, we administered endomorphins locally into the rat brain followed by behavioral and neurochemical examinations. The results indicate that rats pretreated with endomorphin-1 or -2 (5 microg per side for 7 days) in the ventral tegmental area developed locomotor sensitization to the challenge injection of amphetamine (1 mg/kg). On the other hand, when endomorphins were given in the lateral ventricle (20 microg for 5 days) of amphetamine-sensitized rats (5 mg/kg x 14 days) during the withdrawal period (w5-w9), neither peptide had a modulatory effect on locomotor sensitization. Biochemical analyses revealed that treatment with endomorphins in the ventral tegmental area significantly increased the levels of glutamate in the medial prefrontal cortex and ventral and dorsal striatum to levels comparable to those observed in the amphetamine-sensitized rats. In the same animals, endomorphins also caused decreases in the levels of serotonin and its metabolite, 5-hydroxyindoleacetic acid, in the medial prefrontal cortex. Interestingly, although there was no behavioral significance, endomorphin-1 treatment in the lateral ventricle of control and amphetamine-sensitized rats during withdrawal resulted in decreases of GABA, aspartate, dopamine, and its metabolite 3,4-dihydroxyphenylacetic acid in the ventral striatum. We conclude that endomorphins, by stimulating the mu-opioid receptors in the ventral tegmental area, could sensitize the behavioral response to amphetamine. The results also demonstrate that there are differential responses between endomorphin-1 and -2 on

  20. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    OpenAIRE

    Kennard, John A.; Woodruff-Pak, Diana S.

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memo...

  1. Hippocampal volume and sensitivity to maternal aggressive behavior: a prospective study of adolescent depressive symptoms.

    Science.gov (United States)

    Whittle, Sarah; Yap, Marie B H; Sheeber, Lisa; Dudgeon, Paul; Yücel, Murat; Pantelis, Christos; Simmons, Julian G; Allen, Nicholas B

    2011-02-01

    It has been suggested that biological factors confer increased sensitivity to environmental influences on depressive symptoms during adolescence, a crucial time for the onset of depressive disorders. Given the critical role of the hippocampus in sensitivity to stress and processing of contextual aspects of the environment, investigation of its role in determining sensitivity to environmental context seems warranted. This study prospectively examined hippocampal volume as a measure of sensitivity to the influence of aggressive maternal behavior on change in depressive symptoms from early to midadolescence. The interaction between aggressive maternal behavior and hippocampal volume was found to predict change in depressive symptoms. Significant sex differences also emerged, whereby only for girls were larger bilateral hippocampal volumes more sensitive to the effects of maternal aggressive behavior, particularly with respect to experiencing the protective effects of low levels of maternal aggressiveness. These findings help elucidate the complex relationships between brain structure, environmental factors such as maternal parenting style, and sensitivity to (i.e., risk for, and protection from) the emergence of depression during this life stage. Given that family context risk factors are modifiable, our findings suggest the potential utility of targeted parenting interventions for the prevention and treatment of adolescent depressive disorder.

  2. Acute estradiol treatment affects the expression of cocaine-induced conditioned place preference in ovariectomized female rats.

    Science.gov (United States)

    Bobzean, Samara A M; Dennis, Torry S; Perrotti, Linda I

    2014-04-01

    Women and female rodents are more responsive to the subjective effects of psychostimulant drugs of abuse compared to males. A growing body of literature supports a role for estradiol as a mechanism underlying these sex differences. However, little is known about the influence of acute elevations in levels of estradiol on drug conditioned behaviors. The aim of the present study was to evaluate the influence of an acute increase in systemic estradiol levels on the expression of cocaine conditioned place preference (CPP). Using a six day conditioning procedure, ovariectomized (OVX) female rats were conditioned with one of four doses of cocaine (2.5, 5, 10, or 15mg/kg) to associate one of two large chambers of a CPP apparatus with cocaine or saline. Thirty minutes prior to the start of the CPP preference test, rats were pretreated with either 5μg estradiol benzoate (EB) or peanut oil (PO). PO-treated rats expressed a significant preference for only the mid-range conditioning doses of cocaine (5 and 10mg/kg). However, acute EB treatment resulted in a rightward shift in the cocaine dose-response curve; rats demonstrated a significant preference at only the moderate and high conditioning doses of cocaine (10 and 15mg/kg). These findings demonstrate that acute elevations in estradiol may dampen the expression of conditioned responses to cocaine's secondary rewards at lower conditioning doses of the drug and facilitate CPP at higher doses while estradiol deficiency decreases the threshold dose of cocaine necessary to induce CPP.

  3. Neuropsychological Behavioral Inhibition System (BIS) and Behavioral Approach System (BAS) assessment: a shortened Sensitivity to Punishment and Sensitivity to Reward Questionnaire version (SPSRQ-20).

    Science.gov (United States)

    Aluja, Anton; Blanch, Angel

    2011-11-01

    This research was designed to investigate the items and factor structure of the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) proposed by Torrubia, Avila, Moltó, and Caseras ( 2001 ), as a measure of the behavioral inhibition system and behavioral activation system in Gray's reinforcement sensitivity theory. Recent studies that analyzed this instrument by exploratory and confirmatory factor analysis suggest the need for structural refinement. The Spanish version of the SPSRQ was analyzed by exploratory and confirmatory procedures in calibration (n = 2,102) and validation (n = 746) independent samples. In addition, convergent and discriminant validity was evaluated with the Zuckerman-Kuhlman Personality Questionnaire (Zuckerman, Kuhlman, Teta, Joireman, & Kraft, 1993 ), the Impulsiveness, Venturesomeness and Empathy Inventory (S. B. G. Eysenck, Pearson, Easting, & Allsopp, 1985 ) the Neuroticism, Extraversion and Openness Five Factor Inventory (Costa & McCrae, 1992 ), and the Barratt Impulsiveness Scales (Barratt, 1985 ). Results showed the robustness of a 20-item structure of the SPSRQ, with satisfactory fit adjustment, validity, and reliability. The findings are discussed in terms of the better functioning and sound psychometric properties of the SPSRQ 20-item version for Gray's personality theory.

  4. Characterization of SWAT hydrologic parameter sensitivity and behavior across spatial and temporal gradient

    Science.gov (United States)

    Kim, Y.; Hwang, T.; Vose, J. M.; Martin, K. L.; Band, L. E.

    2016-12-01

    Hydrologic models reflect our understanding of factors that regulate stream discharge and range from simple empirical models to highly complex process-based models. Sensitivity analysis is a commonly used tool to detect the parameters that significantly impact model results. In this study, we hypothesized that (1) analysis of patterns in parameter sensitivity could be used to better understand variation in controls on hydrologic behavior within and across a mountain-piedmont-coastal gradient, and (2) shifts in parameter significance among wet, dry, and average precipitation years could reveal differing sensitivities to variation in precipitation. To test our hypotheses, we applied the Soil and Water Assessment Tool (SWAT) to several small headwater sub-watersheds in the Yadkin-Pee Dee basin, located in North and South Carolina, USA. In global sensitivity analyses, we found that main channel routing and curve number for surface runoff parameters were the most significant parameters across all of the study watersheds. Parameters influence on hydrologic behavior varied across the physiographic gradient as well. Soil parameters were more sensitive in the Mountains, while the surface runoff lag coefficient and the plant uptake compensation factor were significant in the Piedmont and Coastal Plain watersheds. The groundwater revap coefficient was significant only in the Piedmont watersheds. We also found noticeable shifts in the behavioral ranges of parameters along the geographical gradient, including surface runoff, main channel routing and soil related parameters. There were also inter-annual variations across the dry, wet, and normal water yield years at the study watersheds. Mountain watersheds exhibited noticeable temporal variation in the behavior of parameters driving evapotranspiration, main channel routing, and soil properties. Two Piedmont watersheds had different temporal variations in parameter behavior, which might be due to the difference in landuse

  5. Testing the role of reward and punishment sensitivity in avoidance behavior: a computational modeling approach.

    Science.gov (United States)

    Sheynin, Jony; Moustafa, Ahmed A; Beck, Kevin D; Servatius, Richard J; Myers, Catherine E

    2015-04-15

    Exaggerated avoidance behavior is a predominant symptom in all anxiety disorders and its degree often parallels the development and persistence of these conditions. Both human and non-human animal studies suggest that individual differences as well as various contextual cues may impact avoidance behavior. Specifically, we have recently shown that female sex and inhibited temperament, two anxiety vulnerability factors, are associated with greater duration and rate of the avoidance behavior, as demonstrated on a computer-based task closely related to common rodent avoidance paradigms. We have also demonstrated that avoidance is attenuated by the administration of explicit visual signals during "non-threat" periods (i.e., safety signals). Here, we use a reinforcement-learning network model to investigate the underlying mechanisms of these empirical findings, with a special focus on distinct reward and punishment sensitivities. Model simulations suggest that sex and inhibited temperament are associated with specific aspects of these sensitivities. Specifically, differences in relative sensitivity to reward and punishment might underlie the longer avoidance duration demonstrated by females, whereas higher sensitivity to punishment might underlie the higher avoidance rate demonstrated by inhibited individuals. Simulations also suggest that safety signals attenuate avoidance behavior by strengthening the competing approach response. Lastly, several predictions generated by the model suggest that extinction-based cognitive-behavioral therapies might benefit from the use of safety signals, especially if given to individuals with high reward sensitivity and during longer safe periods. Overall, this study is the first to suggest cognitive mechanisms underlying the greater avoidance behavior observed in healthy individuals with different anxiety vulnerabilities.

  6. Getting what you want: How fit between desired and received leader sensitivity influences emotion and counterproductive work behavior.

    Science.gov (United States)

    Rupprecht, Elizabeth A; Kueny, Clair Reynolds; Shoss, Mindy K; Metzger, Andrew J

    2016-10-01

    We challenge the intuitive belief that greater leader sensitivity is always associated with desirable outcomes for employees and organizations. Specifically, we argue that followers' idiosyncratic desires for, and perceptions of, leader sensitivity behaviors play a key role in how followers react to their leader's sensitivity. Moreover, these resulting affective experiences are likely to have important consequences for organizations, specifically as they relate to employee counterproductive work behavior (CWB). Drawing from supplies-values (S-V) fit theory and the stressor-emotion model of CWB, the current study focuses on the affective and behavioral consequences of fit between subordinates' ideal leader sensitivity behavior preferences and subordinates' perceptions of their actual leader's sensitivity behaviors. Polynomial regression analyses reveal that congruence between ideal and actual leader sensitivity influences employee negative affect and, consequently, engagement in counterproductive work behavior. (PsycINFO Database Record

  7. Anxiety sensitivity uniquely predicts exercise behaviors in young adults seeking to increase physical activity

    NARCIS (Netherlands)

    Moshier, S.J.; Szuhany, K.L.; Hearon, B.A.; Smits, J.A.J.; Otto, M.W.

    2016-01-01

    Individuals with elevated levels of anxiety sensitivity (AS) may be motivated to avoid aversive emotional or physical states, and therefore may have greater difficulty achieving healthy behavioral change. This may be particularly true for exercise, which produces many of the somatic sensations withi

  8. Sensitivity to Change of Objectively-Derived Measures of Sedentary Behavior

    Science.gov (United States)

    Chastin, Sebastien F. M.; Winkler, Elisabeth A. H.; Eakin, Elizabeth G.; Gardiner, Paul A.; Dunstan, David W.; Owen, Neville; Healy, Genevieve N.

    2015-01-01

    The aim of this study was to examine the sensitivity to change of measures of sedentary behavior derived from body worn sensors in different intervention designs. Results from two intervention studies: "Stand up for Your Health" (pre-post home-based study with older adults not in paid employment) and "Stand Up Comcare"…

  9. Distinguishing between learning and motivation in behavioral tests of the reinforcement sensitivity theory of personality.

    Science.gov (United States)

    Smillie, Luke D; Dalgleish, Len I; Jackson, Chris J

    2007-04-01

    According to Gray's (1973) Reinforcement Sensitivity Theory (RST), a Behavioral Inhibition System (BIS) and a Behavioral Activation System (BAS) mediate effects of goal conflict and reward on behavior. BIS functioning has been linked with individual differences in trait anxiety and BAS functioning with individual differences in trait impulsivity. In this article, it is argued that behavioral outputs of the BIS and BAS can be distinguished in terms of learning and motivation processes and that these can be operationalized using the Signal Detection Theory measures of response-sensitivity and response-bias. In Experiment 1, two measures of BIS-reactivity predicted increased response-sensitivity under goal conflict, whereas one measure of BAS-reactivity predicted increased response-sensitivity under reward. In Experiment 2, two measures of BIS-reactivity predicted response-bias under goal conflict, whereas a measure of BAS-reactivity predicted motivation response-bias under reward. In both experiments, impulsivity measures did not predict criteria for BAS-reactivity as traditionally predicted by RST.

  10. Anxiety sensitivity and working memory capacity: Risk factors and targets for health behavior promotion

    NARCIS (Netherlands)

    Otto, M.W.; Eastman, A.; Lo, S.; Hearon, B.A.; Bickel, W.K.; Zvolensky, M.J.; Smits, J.A.J.; Doan, S.N.

    2016-01-01

    Understanding the nature and influence of specific risk profiles is increasingly important for health behavior promotion. The purpose of this article is to document the value of two factors - anxiety sensitivity (AS) and working memory capacity (WMC) - for enhancing risk for the initiation and/or ma

  11. A sensitivity analysis on the springback behavior of the Unconstrained Bending Problem

    NARCIS (Netherlands)

    Meinders, T.; Konter, A.W.A.; Meijers, S.E.; Atzema, E.H.; Kappert, H.

    2006-01-01

    Sheet metal forming software is commonly used in the automotive and sheet metal sectors to support the design stage. However, the ability of the currently available software to accurately predict springback is limited. A sensitivity analysis of the springback behavior of a simple product is performe

  12. A complex interplay between personality domains, marital status and a variant in CHRNA5 on the risks of cocaine, nicotine dependences and cocaine-induced paranoia.

    Directory of Open Access Journals (Sweden)

    Tetyana Zayats

    Full Text Available BACKGROUND: Personality correlates highly with both cocaine and nicotine dependencies (CD, ND, and their co-morbid psychopathologies. However, little is known about the nature of these relationships. This study examined if environment (marriage or genetics (a single SNP, CHRNA5*rs16969968 would moderate the correlation of personality with CD, ND and cocaine-induced paranoia (CIP in African and European Americans (AAs, EAs. METHODS: 1432 EAs and 1513 AAs were examined using logistic regression. Personality was assessed by NEO-PI-R, while CD, ND and CIP were diagnosed according to DSM-IV. ND and CD were examined as binary traits and for the analysis of CIP, subjects were divided into 3 groups: (A Controls with no CIP; (B CD cases without CIP; and (C CD cases with CIP. Multiple testing was Bonferroni-corrected. RESULTS: For CD and ND in the EA population, marital status proved to be a significant moderator in their relationship with openness only (OR = 1.90, 95%CI = 1.36-2.64, p = 1.54e-04 and OR = 2.12, 95%CI = 1.52-2.90, p = 4.65e-06 respectively. For CIP, marriage was observed to moderate its correlation with openness and neuroticism (OR = 1.39, 95%CI = 1.18-1.63, p = 7.64e-04 and OR = 1.26, 95%CI = 1.12-1.42, p = 1.27e-03 respectively. The correlations moderated by rs16969968 were those of conscientiousness and CD (OR = 1.62, 95%CI: 1.23-2.12, p = 8.94e-04 as well as CIP (OR = 1.21, 95%CI: 1.11-1.32, p = 4.93e-04 when comparing group A versus group C. No significant interactions were observed in AA population. The Bonferroni-corrected significance threshold was set to be 1.67e-03. CONCLUSION: The role of personality in CD and CIP may be interceded by both environment and genetics, while in ND by environment only.

  13. Pineal photoreceptor cells are required for maintaining the circadian rhythms of behavioral visual sensitivity in zebrafish.

    Directory of Open Access Journals (Sweden)

    Xinle Li

    Full Text Available In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity.

  14. Behavioral cross-sensitization between morphine-induced locomotion and sodium depletion-induced salt appetite.

    Science.gov (United States)

    Na, Elisa S; Morris, Michael J; Johnson, Alan Kim

    2009-10-01

    In general terms, sensitization refers to the capacity of a repetitive stimulus of fixed strength to produce a progressive increase in the magnitude of a response with each stimulation. In the addiction literature cross-sensitization is the capacity of an agent with abuse potential to sensitize a behavioral response induced by another stimulus. In the present experiments we examined the effects of morphine pretreatment on furosemide-induced saline intake and conversely sodium appetite induction on morphine-induced locomotion. In an initial experiment rats were pretreated with morphine (10 mg/kg, s.c.) or vehicle for 5 days. The rats were then sodium or sham depleted and 24 h later given a sodium appetite test. Sodium depleted rats pretreated with morphine increased saline intake compared to depleted rats initially pretreated with vehicle. In a second experiment rats that were previously depleted and repleted of sodium as compared to sham depleted animals showed enhanced locomotor activity in an open field test when challenged with morphine (1 mg/kg, s.c.). These studies demonstrate that the behavioral responses induced by sodium deficiency and morphine treatment cross-sensitize with one another and suggest that common neural substrates underlie the sensitization of behaviors associated with states induced by morphine and sodium appetite.

  15. NMDA receptors on non-dopaminergic neurons in the VTA support cocaine sensitization.

    Directory of Open Access Journals (Sweden)

    Yu Luo

    Full Text Available BACKGROUND: The initiation of behavioral sensitization to cocaine and other psychomotor stimulants is thought to reflect N-methyl-D-aspartate receptor (NMDAR-mediated synaptic plasticity in the mesolimbic dopamine (DA circuitry. The importance of drug induced NMDAR mediated adaptations in ventral tegmental area (VTA DA neurons, and its association with drug seeking behaviors, has recently been evaluated in Cre-loxp mice lacking functional NMDARs in DA neurons expressing Cre recombinase under the control of the endogenous dopamine transporter gene (NR1(DATCre mice. METHODOLOGY AND PRINCIPAL FINDINGS: Using an additional NR1(DATCre mouse transgenic model, we demonstrate that while the selective inactivation of NMDARs in DA neurons eliminates the induction of molecular changes leading to synaptic strengthening, behavioral measures such as cocaine induced locomotor sensitization and conditioned place preference remain intact in NR1(DATCre mice. Since VTA DA neurons projecting to the prefrontal cortex and amygdala express little or no detectable levels of the dopamine transporter, it has been speculated that NMDA receptors in DA neurons projecting to these brain areas may have been spared in NR1(DATCre mice. Here we demonstrate that the NMDA receptor gene is ablated in the majority of VTA DA neurons, including those exhibiting undetectable DAT expression levels in our NR1(DATCre transgenic model, and that application of an NMDAR antagonist within the VTA of NR1(DATCre animals still blocks sensitization to cocaine. CONCLUSIONS/SIGNIFICANCE: These results eliminate the possibility of NMDAR mediated neuroplasticity in the different DA neuronal subpopulations in our NR1(DATCre mouse model and therefore suggest that NMDARs on non-DA neurons within the VTA must play a major role in cocaine-related addictive behavior.

  16. An inexpensive, scalable behavioral assay for measuring ethanol sedation sensitivity and rapid tolerance in Drosophila.

    Science.gov (United States)

    Sandhu, Simran; Kollah, Arnavaz P; Lewellyn, Lara; Chan, Robin F; Grotewiel, Mike

    2015-04-15

    Alcohol use disorder (AUD) is a serious health challenge. Despite a large hereditary component to AUD, few genes have been unambiguously implicated in their etiology. The fruit fly, Drosophila melanogaster, is a powerful model for exploring molecular-genetic mechanisms underlying alcohol-related behaviors and therefore holds great promise for identifying and understanding the function of genes that influence AUD. The use of the Drosophila model for these types of studies depends on the availability of assays that reliably measure behavioral responses to ethanol. This report describes an assay suitable for assessing ethanol sensitivity and rapid tolerance in flies. Ethanol sensitivity measured in this assay is influenced by the volume and concentration of ethanol used, a variety of previously reported genetic manipulations, and also the length of time the flies are housed without food immediately prior to testing. In contrast, ethanol sensitivity measured in this assay is not affected by the vigor of fly handling, sex of the flies, and supplementation of growth medium with antibiotics or live yeast. Three different methods for quantitating ethanol sensitivity are described, all leading to essentially indistinguishable ethanol sensitivity results. The scalable nature of this assay, combined with its overall simplicity to set-up and relatively low expense, make it suitable for small and large scale genetic analysis of ethanol sensitivity and rapid tolerance in Drosophila.

  17. The link between hypomania risk and creativity: The role of heightened behavioral activation system (BAS) sensitivity.

    Science.gov (United States)

    Kim, Bin-Na; Kwon, Seok-Man

    2017-06-01

    The relationship between bipolar disorder (BD) and creativity is well-known; however, relatively little is known about its potential mechanism. We investigated whether heightened behavioral activation system (BAS) sensitivity may mediate such relationship. Korean young adults (N=543) completed self-report questionnaires that included the Hypomanic Personality Scale (HPS), the Behavioral Activation System(BAS) Scale, the Everyday Creativity Scale (ECS), the Positive Affect and Negative Affect Schedule (PANAS), and the Altman Self-Rating Mania Scale (ASRM). Correlational, hierarchical regression and mediation analyses using bootstrap confidence intervals were conducted. As predicted, BAS sensitivity was associated with self-reported creativity as well as hypomania risk and symptoms. Even when positive affect was controlled, BAS sensitivity predicted incrementally significant variance in explaining creativity. In mediation analysis, BAS sensitivity partially mediated the relation between hypomania risk and creativity. Reliance on self-report measures in assessing creativity and usage of non-clinical sample. BAS sensitivity was related not only to mood pathology but also to creativity. As a basic affective temperament, BAS sensitivity may help explain incompatible sides of adaptation associated with BD. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Ablation of kappa-opioid receptors from brain dopamine neurons has anxiolytic-like effects and enhances cocaine-induced plasticity.

    Science.gov (United States)

    Van't Veer, Ashlee; Bechtholt, Anita J; Onvani, Sara; Potter, David; Wang, Yujun; Liu-Chen, Lee-Yuan; Schütz, Günther; Chartoff, Elena H; Rudolph, Uwe; Cohen, Bruce M; Carlezon, William A

    2013-07-01

    Brain kappa-opioid receptors (KORs) are implicated in states of motivation and emotion. Activation of KORs negatively regulates mesolimbic dopamine (DA) neurons, and KOR agonists produce depressive-like behavioral effects. To further evaluate how KOR function affects behavior, we developed mutant mice in which exon 3 of the KOR gene (Oprk1) was flanked with Cre-lox recombination (loxP) sites. By breeding these mice with lines that express Cre-recombinase (Cre) in early embryogenesis (EIIa-Cre) or only in DA neurons (dopamine transporter (DAT)-Cre), we developed constitutive KOR knockouts (KOR(-/-)) and conditional knockouts that lack KORs in DA-containing neurons (DAT-KOR(lox/lox)). Autoradiography demonstrated complete ablation of KOR binding in the KOR(-/-) mutants, and reduced binding in the DAT-KOR(lox/lox) mutants. Quantitative reverse transcription PCR (qPCR) studies confirmed that KOR mRNA is undetectable in the constitutive mutants and reduced in the midbrain DA systems of the conditional mutants. Behavioral characterization demonstrated that these mutant lines do not differ from controls in metrics, including hearing, vision, weight, and locomotor activity. Whereas KOR(-/-) mice appeared normal in the open field and light/dark box tests, DAT-KOR(lox/lox) mice showed reduced anxiety-like behavior, an effect that is broadly consistent with previously reported effects of KOR antagonists. Sensitization to the locomotor-stimulating effects of cocaine appeared normal in KOR(-/-) mutants, but was exaggerated in DAT-KOR(lox/lox) mutants. Increased sensitivity to cocaine in the DAT-KOR(lox/lox) mutants is consistent with a role for KORs in negative regulation of DA function, whereas the lack of differences in the KOR(-/-) mutants suggests compensatory adaptations after constitutive receptor ablation. These mouse lines may be useful in future studies of KOR function.

  19. Interoceptive sensitivity, body weight and eating behavior in children: A prospective study

    Directory of Open Access Journals (Sweden)

    Anne eKoch

    2014-09-01

    Full Text Available Previous research indicates that interindividual differences in the ability to perceive one’s own bodily signals (interoceptive sensitivity, IS are associated with disordered eating behavior and weight problems. But representative and prospective data in children are lacking and therefore, the exact nature of these observed associations remains unclear. Data on IS measured by heartbeat perception ability in 1657 children between 6 and 11 years of age were collected on the basis of two measurement points with a year distance in time. Stability of the construct and its prospective association with different food approach behaviors (assessed via parent questionnaires (Children`s Eating Behavior Questionnaire and Dutch Eating Behavior Questionnaire as well as with weight status were analyzed via structural equation modeling. Main results were that only in overweight children external and emotional eating behavior were predictive for later IS, whereas no such relation was found in normal weight children. There was no direct relation between IS and body mass index. For the first time, we could show that eating behavior and IS in middle childhood are prospectively related to each other. But surprisingly, our data indicate that altered interoceptive processes rather follow than precede non-adaptive eating behavior patterns in overweight children. This suggests a possible crucial role of faulty learning mechanisms in eating behavior early in life, undermining the later confidence in one’s body.

  20. Interoceptive sensitivity, body weight and eating behavior in children: a prospective study.

    Science.gov (United States)

    Koch, Anne; Pollatos, Olga

    2014-01-01

    Previous research indicates that interindividual differences in the ability to perceive one's own bodily signals (interoceptive sensitivity, IS) are associated with disordered eating behavior and weight problems. But representative and prospective data in children are lacking and therefore, the exact nature of these observed associations remains unclear. Data on IS measured by heartbeat perception ability in 1657 children between 6 and 11 years of age were collected on the basis of two measurement points with a year distance in time. Stability of the construct and its prospective association with different food approach behaviors [assessed via parent questionnaires (Children's Eating Behavior Questionnaire and Dutch Eating Behavior Questionnaire)] as well as with weight status were analyzed via structural equation modeling. Main results were that only in overweight children external and emotional eating behavior were predictive for later IS, whereas no such relation was found in normal weight children. There was no direct relation between IS and body mass index. For the first time, we could show that eating behavior and IS in middle childhood are prospectively related to each other. But surprisingly, our data indicate that altered interoceptive processes rather follow than precede non-adaptive eating behavior patterns in overweight children. This suggests a possible crucial role of faulty learning mechanisms in eating behavior early in life, undermining the later confidence in one's body.

  1. Body weight status, eating behavior, sensitivity to reward/punishment, and gender: relationships and interdependencies.

    Science.gov (United States)

    Dietrich, Anja; Federbusch, Martin; Grellmann, Claudia; Villringer, Arno; Horstmann, Annette

    2014-01-01

    Behavioral and personality characteristics are factors that may jointly regulate body weight. This study explored the relationship between body mass index (BMI) and self-reported behavioral and personality measures. These measures included eating behavior (based on the Three-Factor Eating Questionnaire; Stunkard and Messick, 1985), sensitivity to reward and punishment (based on the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales) (Carver and White, 1994) and self-reported impulsivity (based on the Barratt Impulsiveness Scale-11; Patton et al., 1995). We found an inverted U-shaped relationship between restrained eating and BMI. This relationship was moderated by the level of disinhibited eating. Independent of eating behavior, BIS and BAS responsiveness were associated with BMI in a gender-specific manner with negative relationships for men and positive relationships for women. Together, eating behavior and BIS/BAS responsiveness accounted for a substantial proportion of BMI variance (men: ∼25%, women: ∼32%). A direct relationship between self-reported impulsivity and BMI was not observed. In summary, our results demonstrate a system of linear and non-linear relationships between the investigated factors and BMI. Moreover, body weight status was not only associated with eating behavior (cognitive restraint and disinhibition), but also with personality factors not inherently related to an eating context (BIS/BAS). Importantly, these relationships differ between men and women.

  2. Spectral Dependent Photoelectrochemical Behaviors of CdS Sensitized ZnO Nanorods.

    Science.gov (United States)

    Majumder, T; Hmar, J J L; Roy, J N; Mondal, S P

    2016-04-01

    CdS decorated ZnO nanorods have been grown by a combination of hydrothermal method and successive ion layer absorption and reaction (SILAR) method. Optical absorption and emission properties of ZnO nanorods have been studied after sensitization with CdS nanoparticles. Current-voltage characteristics of ZnO nanorods and CdS sensitized ZnO nanorods have been studied in an electrochemical cell. The spectral dependent photocurrent and photopotential behaviors of ZnO nanorods and CdS sensitized ZnO nanorods have been investigated using monochromatic light of wavelength 300-700 nm. The photopotential recovery time have been estimated for CdS sensitized nanorods and pristine nanorods.

  3. Sensitivity, child regulatory processes, and naturally occurring declines in antisocial behavior across childhood.

    Science.gov (United States)

    Buck, Katharine Ann

    2014-12-01

    Despite considerable research on why antisocial behavior develops and interventions that reduce it, aspects of everyday family processes that may promote naturally occurring declines in antisocial behavior or that may result from such declines in most children without intervention are poorly understood. The current study explored family processes that may enable children to replace antisocial tendencies and the effects that declines in antisocial behavior may have on parenting and child regulatory processes. Longitudinal data from 1,022 children (54 months-6th grade) from the NICHD Study of Early Child Care and Youth Development were examined. Findings demonstrated that naturally occurring declines in antisocial behavior both predicted and were predicted by maternal sensitivity, emotion regulation, and social skills. These declines predicted but were not predicted by declines in hostile attributions. The data revealed multiple indirect paths, which highlight the complex nature of these variables across development.

  4. Differential behavioral sensitivity to carbon dioxide (CO2) inhalation in rats.

    Science.gov (United States)

    Winter, Andrew; Ahlbrand, Rebecca; Naik, Devanshi; Sah, Renu

    2017-03-27

    Inhalation of carbon dioxide (CO2) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO2 reliably evokes panic attacks. Sensitivity to CO2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. Preclinical models that can simulate differential responsivity to CO2 are therefore relevant. In the current study we investigated CO2-evoked behavioral responses in four different rat strains: Sprague-Dawley (SD), Wistar (W), Long Evans (LE) and Wistar-Kyoto, (WK) rats. We also assessed tryptophan hydroxylase 2 (TPH-2)-positive serotonergic neurons in anxiety/panic regulatory subdivisions of the dorsal raphe nucleus (DR), as well as dopamine β hydroxylase (DβH)-positive noradrenergic neurons in the locus coeruleus, implicated in central CO2-chemosensitivity. Behavioral responsivity to CO2 inhalation varied between strains. CO2-evoked immobility was significantly higher in LE and WK rats as compared with W and SD cohorts. Differences were also observed in CO2-evoked rearing and grooming behaviors. Exposure to CO2 did not produce conditioned behavioral responses upon re-exposure to CO2 context in any strain. Reduced TPH-2-positive cell counts were observed specifically in the panic-regulatory dorsal raphe ventrolateral (DRVL)-ventrolateral periaqueductal gray (VLPAG) subdivision in CO2-sensitive strains. Conversely, DβH-positive cell counts within the LC were significantly higher in CO2-sensitive strains. Collectively, our data provide evidence for strain dependent, differential CO2-sensitivity and potential differences in monoaminergic systems regulating panic and anxiety. Comparative studies between CO2-vulnerable and resistant strains may facilitate the mechanistic understanding of differential CO2-sensitivity in the development of panic and anxiety disorders.

  5. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

    Directory of Open Access Journals (Sweden)

    Yoshio Iguchi

    Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  6. Anxiety sensitivity and working memory capacity: Risk factors and targets for health behavior promotion.

    Science.gov (United States)

    Otto, Michael W; Eastman, Abraham; Lo, Stephen; Hearon, Bridget A; Bickel, Warren K; Zvolensky, Michael; Smits, Jasper A J; Doan, Stacey N

    2016-11-01

    Understanding the nature and influence of specific risk profiles is increasingly important for health behavior promotion. The purpose of this article is to document the value of two factors-anxiety sensitivity (AS) and working memory capacity (WMC)-for enhancing risk for the initiation and/or maintenance of a range of negative health behaviors. AS is a distress-related risk factor that potentiates avoidance/coping motivations for negative health behaviors. Stress provides the conditions for negative somatic and affective states, and AS amplifies the aversiveness of these experiences and correspondingly hinders adaptive functioning. In contrast, low WMC is hypothesized to exert its effect by decreasing the capacity to filter out current temptations, attenuating a focus on longer-term goals and impairing the application of relevant coping skills at times of stress. In this review, we provide conceptual models for the separate roles of high AS and low WMC in negative health behaviors, review the influence of these factors on specific health behavior exemplars (eating behaviors/obesity, physical activity, smoking, alcohol use, and sleep promotion), provide preliminary evidence for their value as independent treatment targets for health-behavior promotion, and encourage specific research directions in relation to these variables. Copyright © 2016. Published by Elsevier Ltd.

  7. Group cognitive-behavioral therapy for depression in Spanish: culture-sensitive manualized treatment in practice.

    Science.gov (United States)

    Aguilera, Adrian; Garza, Monica J; Muñoz, Ricardo F

    2010-08-01

    The authors applied cognitive-behavioral therapy (CBT) for depression using the Healthy Management of Reality treatment manual. This 16-week group treatment comprised four 4-week modules: thoughts (cognitive restructuring), activities (behavioral activation), people (interpersonal skills training), and health (addresses physical health and depression). They illustrated the use of the culture-sensitive treatment manuals by way of the member characteristics and clinical process of a Spanish-language CBT group for depression. They highlighted the challenges and satisfactions of working with a Spanish-speaking population in the public sector, and focused on how culture and socioeconomic status influence patients, and how to adapt treatment to these factors. Last, they demonstrated how technological advances integrate with culture-sensitive, evidence-based treatments to better serve this population and reduce disparities.

  8. Coupling behavior of the pH/temperature sensitive hydrogels for the inhomogeneous and homogeneous swelling

    Science.gov (United States)

    Mazaheri, H.; Baghani, M.; Naghdabadi, R.; Sohrabpour, S.

    2016-08-01

    In this work, a model is developed to continuously predict homogeneous and inhomogeneous swelling behavior of pH/temperature sensitive PNIPAM hydrogels. Employing the model, homogeneous swelling of the pH/temperature sensitive hydrogel is investigated for free and biaxial constrained swelling cases. Comparing the model results with the experimental data available in the literature, the validity of the model is confirmed. The model is then employed to investigate inhomogeneous swelling of a spherical shell on a hard core both analytically and numerically for pH or temperature variations. In this regard, numerical tools are developed via preparing a user defined subroutine in ABAQUS software. Then, the complicated problem of contact between the hydrogel shell and a micro-channel with rigid walls is also investigated. Considering the results, we can say that the model is applicable for solving engineering boundary value problem of pH/temperature sensitive hydrogels.

  9. Size determines antennal sensitivity and behavioral threshold to odors in bumblebee workers

    Science.gov (United States)

    Spaethe, Johannes; Brockmann, Axel; Halbig, Christine; Tautz, Jürgen

    2007-09-01

    The eusocial bumblebees exhibit pronounced size variation among workers of the same colony. Differently sized workers engage in different tasks (alloethism); large individuals are found to have a higher probability to leave the colony and search for food, whereas small workers tend to stay inside the nest and attend to nest duties. We investigated the effect of size variation on morphology and physiology of the peripheral olfactory system and the behavioral response thresholds to odors in workers of Bombus terrestris. Number and density of olfactory sensilla on the antennae correlate significantly with worker size. Consistent with these morphological changes, we found that antennal sensitivity to odors increases with body size. Antennae of large individuals show higher electroantennogram responses to a given odor concentration than those of smaller nestmates. This finding indicates that large antennae exhibit an increased capability to catch odor molecules and thus are more sensitive to odors than small antennae. We confirmed this prediction in a dual choice behavioral experiment showing that large workers indeed are able to respond correctly to much lower odor concentrations than small workers. Learning performance in these experiments did not differ between small and large bumblebees. Our results clearly show that, in the social bumblebees, variation in olfactory sensilla number due to size differences among workers strongly affects individual odor sensitivity. We speculate that superior odor sensitivity of large workers has favored size-related division of labor in bumblebee colonies.

  10. Body weight status, eating behavior, sensitivity to reward/punishment, and gender: relationships and interdependencies

    Directory of Open Access Journals (Sweden)

    Anja eDietrich

    2014-10-01

    Full Text Available Behavioral and personality characteristics are factors that may jointly regulate body weight. This study explored the relationship between body mass index (BMI and self-reported behavioral and personality measures. These measures included eating behavior (based on the Three-Factor Eating Questionnaire- TFEQ (Stunkard and Messick, 1985, sensitivity to reward and punishment (based on the BIS/BAS Scales (Carver and White, 1994 and self-reported impulsivity (based on the Barratt Impulsiveness Scale-11 (Patton et al., 1995. We found an inverted U-shaped relationship between restrained eating and BMI. This relationship was moderated by the level of disinhibited eating. Independent of eating behavior, BIS and BAS responsiveness were associated with BMI in a gender-specific manner with negative relationships for men and positive relationships for women. Together, eating behavior and BIS/BAS responsiveness accounted for a substantial proportion of BMI variance (men: ~25%, women: ~32%. A direct relationship between self-reported impulsivity and BMI was not observed. In summary, our results demonstrate a system of linear and non-linear relationships between the investigated factors and BMI. Moreover, body weight status was not only associated with eating behavior (cognitive restraint and disinhibition, but also with personality factors not inherently related to an eating context (BIS/BAS. Importantly, these relationships differ between men and women.

  11. How reinforcement sensitivity and perceived risk influence young drivers' reported engagement in risky driving behaviors.

    Science.gov (United States)

    Harbeck, Emma L; Glendon, A Ian

    2013-05-01

    Gray's reinforcement sensitivity theory (RST), implementing Carver and White's behavior inhibition system (BIS) and behavior approach system (BAS) scales, was used to predict reported engagement in 10 risky driving behaviors: speeding (2 levels), driving under the influence of alcohol, racing other vehicles, cell phone use (hand-held and hands free), tailgating, unsafe overtaking, driving while fatigued, and not wearing a seatbelt. Participants were 165 young male and female (n=101) drivers aged 17-25 years who held a valid Australian driver's license. Effects of the explanatory variables and specific risk perceptions upon engagement in the reported risky driving behaviors were examined using SEM analyses. Also of interest was whether perceived risk mediated the relationship between the personality variables and reported engagement in risky driving behaviors. RST variables, negative reactivity, reward responsiveness and fun seeking, accounted for unique variance in young drivers' perceived risk. Reward responsiveness and perceived risk accounted for unique variance in young drivers' reported engagement in risky driving behaviors. Negative reactivity was completely mediated by perceived risk in its negative relationship with reported engagement. To better understand driving related risk decision making, future research could usefully incorporate drivers' motivation systems. This has the potential to lead to more tailored approaches to identifying risk-prone drivers and provide information for the development and implementation of media campaigns and educational programs.

  12. Failure to retreat: Blunted sensitivity to negative feedback supports risky behavior in adolescents.

    Science.gov (United States)

    McCormick, Ethan M; Telzer, Eva H

    2017-02-15

    Decision-making processes rarely occur in isolation. Rather, representations are updated constantly based on feedback to past decisions and actions. However, previous research has focused on the reaction to feedback receipt itself, instead of examining how feedback information is integrated into future decisions. In the current study, we examined differential neural sensitivity during risk decisions following positive versus negative feedback in a risk-taking context, and how this differential sensitivity is linked to adolescent risk behavior. Fifty-eight adolescents (ages 13-17 years) completed the Balloon Analogue Risk Task (BART) during an fMRI session and reported on their levels of risk-taking behavior. Results show that reduced medial PFC (mPFC) response following negative versus positive feedback is associated with fewer reductions in task-based risky decisions following negative feedback, as well as increased self-reported risk-taking behavior. These results suggest that reduced neural integration of negative feedback into during future decisions supports risky behavior, perhaps by discounting negative relative to positive feedback information when making subsequent risky decisions.

  13. Effects of adolescent caffeine consumption on cocaine sensitivity.

    Science.gov (United States)

    O'Neill, Casey E; Levis, Sophia C; Schreiner, Drew C; Amat, Jose; Maier, Steven F; Bachtell, Ryan K

    2015-03-01

    Caffeine is the most commonly used psychoactive substance, and consumption by adolescents has risen markedly in recent years. We identified the effects of adolescent caffeine consumption on cocaine sensitivity and determined neurobiological changes within the nucleus accumbens (NAc) that may underlie caffeine-induced hypersensitivity to cocaine. Male Sprague-Dawley rats consumed caffeine (0.3 g/l) or water for 28 days during adolescence (postnatal day 28-55; P28-P55) or adulthood (P67-P94). Testing occurred in the absence of caffeine during adulthood (P62-82 or P101-121). Cocaine-induced and quinpirole (D2 receptor agonist)-induced locomotion was enhanced in rats that consumed caffeine during adolescence. Adolescent consumption of caffeine also enhanced the development of a conditioned place preference at a sub-threshold dose of cocaine (7.5 mg/kg, i.p.). These behavioral changes were not observed in adults consuming caffeine for an equivalent period of time. Sucrose preferences were not altered in rats that consumed caffeine during adolescence, suggesting there are no differences in natural reward. Caffeine consumption during adolescence reduced basal dopamine levels and augmented dopamine release in the NAc in response to cocaine (5 mg/kg, i.p.). Caffeine consumption during adolescence also increased the expression of the dopamine D2 receptor, dopamine transporter, and adenosine A1 receptor and decreased adenosine A2A receptor expression in the NAc. Consumption of caffeine during adulthood increased adenosine A1 receptor expression in the NAc, but no other protein expression changes were observed. Together these findings suggest that caffeine consumption during adolescence produced changes in the NAc that are evident in adulthood and may contribute to increases in cocaine-mediated behaviors.

  14. Age sensitivity of behavioral tests and brain substrates of normal aging in mice.

    Science.gov (United States)

    Kennard, John A; Woodruff-Pak, Diana S

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  15. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    Directory of Open Access Journals (Sweden)

    John A. Kennard

    2011-05-01

    Full Text Available Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  16. Sensitive Periods, Vasotocin-Family Peptides, and the Evolution and Development of Social Behavior

    Directory of Open Access Journals (Sweden)

    Nicole M. Baran

    2017-08-01

    Full Text Available Nonapeptides, by modulating the activity of neural circuits in specific social contexts, provide an important mechanism underlying the evolution of diverse behavioral phenotypes across vertebrate taxa. Vasotocin-family nonapeptides, in particular, have been found to be involved in behavioral plasticity and diversity in social behavior, including seasonal variation, sexual dimorphism, and species differences. Although nonapeptides have been the focus of a great deal of research over the last several decades, the vast majority of this work has focused on adults. However, behavioral diversity may also be explained by the ways in which these peptides shape neural circuits and influence social processes during development. In this review, I synthesize comparative work on vasotocin-family peptides during development and classic work on early forms of social learning in developmental psychobiology. I also summarize recent work demonstrating that early life manipulations of the nonapeptide system alter attachment, affiliation, and vocal learning in zebra finches. I thus hypothesize that vasotocin-family peptides are involved in the evolution of social behaviors through their influence on learning during sensitive periods in social development.

  17. 多巴胺受体在可卡因诱导的转录因子CREB活化中的作用%Dopamine receptors oppositely regulate cocaine-induced transcription factor CREB activation

    Institute of Scientific and Technical Information of China (English)

    刘怒云; 张琳; 王小宁; 张璐

    2006-01-01

    Objective To study the role of dopamine receptors in the regulation of the activity of transcription factor cAMP response element-binding protein (CREB) after cocaine treatment. Methods By using dopamine receptor antagonists SCH23390 and nafadotride, the activation of CREB by D1 and D3 dopamine receptors after cocaine treatment and role of extracellular signal-regulated kinase (ERK) in cocaine-induced CREB activation were examined by Western blotting, which was also employed for determination of the effect of SCH23390 and nafadotride on CREB activation. Results D1 receptor antagonist could inhibit cocaine-induced CREB activation, while D3 receptor antagonist enhanced cocaine-induced CREB activation. Dopamine receptor antagonists SCH23390 and nafadotride did not induce CREB activation. SL327, a MEK inhibitor, inhibited cocaine-induced CREB activation. Conclusion D1 and D3 dopamine receptors can oppositely regulate CREB activation after cocaine treatment and this regulation depends on ERK signaling pathway.%目的研究多巴胺受体在可卡因诱导的转录因子CREB磷酸化活化中的调控作用.方法采用D1和D3多巴胺受体抑制剂,应用Western blotting检测D1与D3多巴胺受体在可卡因诱导的cAMP反应元件结合蛋白(CREB)磷酸化活化中的作用及D1和D3多巴胺受体抑制剂本身对CREB磷酸化活化的影响,进一步应用Westernblotting检测细胞外信号调节激酶(ERK)在CREB磷酸化活化中的作用.结果 D1多巴胺受体抑制剂阻止可卡因诱导的CREB磷酸化活化,而D3多巴胺受体抑制剂促进可卡因诱导的CREB磷酸化活化,D1和D3多巴胺受体抑制剂本身不能诱导CREB磷酸化活化.MEK的特异性抑制剂SL327可以抑制可卡因诱导的CREB磷酸化活化.结论 D1和D3多巴胺受体对CREB的磷酸化活化起反式调控作用,并且这种反式调控作用依赖于ERK信号通路.

  18. Cohort removal induces changes in body temperature, pain sensitivity, and anxiety-like behavior

    Directory of Open Access Journals (Sweden)

    Keizo eTakao

    2016-06-01

    Full Text Available Mouse behavior is analyzed to elucidate the effects of various experimental manipulations, including gene mutation and drug administration. When the effect of a factor of interest is assessed, other factors, such as age, sex, temperature, apparatus, and housing, are controlled in experiments by matching, counterbalancing, and/or randomizing. One such factor that has not attracted much attention is the effect of sequential removal of animals from a common cage (cohort removal. Here we evaluated the effects of cohort removal on rectal temperature, pain sensitivity, and anxiety-like behavior by analyzing the combined data of a large number of C57BL/6J mice that we collected using a comprehensive behavioral test battery. Rectal temperature increased in a stepwise manner according to the position of sequential removal from the cage, consistent with previous reports. In the hot plate test, the mice that were removed first from the cage had a significantly longer latency to show the first paw response than the mice removed later. In the elevated plus maze, the mice removed first spent significantly less time on the open arms compared to the mice removed later. The results of the present study demonstrated that cohort removal induces changes in body temperature, pain sensitivity, and anxiety-like behavior in mice. Cohort removal also increased the plasma corticosterone concentration in mice. Thus, the ordinal position in the sequence of removal from the cage should be carefully counterbalanced between groups when the effect of experimental manipulations, including gene manipulation and drug administration, are examined using behavioral tests.

  19. Cohort Removal Induces Changes in Body Temperature, Pain Sensitivity, and Anxiety-Like Behavior.

    Science.gov (United States)

    Takao, Keizo; Shoji, Hirotaka; Hattori, Satoko; Miyakawa, Tsuyoshi

    2016-01-01

    Mouse behavior is analyzed to elucidate the effects of various experimental manipulations, including gene mutation and drug administration. When the effect of a factor of interest is assessed, other factors, such as age, sex, temperature, apparatus, and housing, are controlled in experiments by matching, counterbalancing, and/or randomizing. One such factor that has not attracted much attention is the effect of sequential removal of animals from a common cage (cohort removal). Here we evaluated the effects of cohort removal on rectal temperature, pain sensitivity, and anxiety-like behavior by analyzing the combined data of a large number of C57BL/6J mice that we collected using a comprehensive behavioral test battery. Rectal temperature increased in a stepwise manner according to the position of sequential removal from the cage, consistent with previous reports. In the hot plate test, the mice that were removed first from the cage had a significantly longer latency to show the first paw response than the mice removed later. In the elevated plus maze, the mice removed first spent significantly less time on the open arms compared to the mice removed later. The results of the present study demonstrated that cohort removal induces changes in body temperature, pain sensitivity, and anxiety-like behavior in mice. Cohort removal also increased the plasma corticosterone concentration in mice. Thus, the ordinal position in the sequence of removal from the cage should be carefully counterbalanced between groups when the effect of experimental manipulations, including gene manipulation and drug administration, are examined using behavioral tests.

  20. Correlations of health behaviors and factors with high sensitivity C-reactive protein in diabetic population

    Directory of Open Access Journals (Sweden)

    Jin-hong HOU

    2013-11-01

    Full Text Available Objective To explore the correlations of ideal cardiovascular health behaviors and factors with the level of high sensitivity C-reactive protein (hsCRP in diabetic population. Methods A cross-sectional method was used in present study. Seven thousand eight hundred and sixty-nine workers with diabetes were recruited who participated in the 2006-2007 Kailuan health examination without history of cerebral and myocardial infarction and without data incompleted. All the information was obtained from the unified questionnaire and measurement of blood biochemistry. Multivariate logistic regression analysis was used to analyze the effects of ideal cardiovascular health behaviors and factors on the level of hsCRP. Results The hsCRP concentrations decreased with the increasing numbers of ideal cardiovascular health behaviors and factors, the medians of hsCRP concentrations were 1.16mg/L, 1.11mg/L, 0.90mg/L and 0.76mg/L in 0-1, 2, 3 and 4-6 ideal cardiovascular health groups, respectively (P<0.01. Multivariate logistic regression analysis showed that, after adjustment by age, gender, triglyceride, low density lipoprotein cholesterol (LDL-C and high density lipoprotein cholesterol (HDL-C, the risk of hsCRP level exceeding 3mg/L in the subjects having 3 and 4-6 ideal cardiovascular health behaviors and factors was 0.60 times (95%CI 0.50-0.72 and 0.45 times (95%CI 0.34-0.61, respectively, than those having 0-1 ideal cardiovascular health behaviors and factors. Conclusion The hsCRP concentrations decreased with increasing numbers of ideal cardiovascular health behaviors and factors; the risk of hsCRP exceeding 3mg/L can be reduced by ideal cardiovascular health behaviors and factors. DOI: 10.11855/j.issn.0577-7402.2013.10.013

  1. The algorithmic complexity of multichannel EEGs is sensitive to changes in behavior.

    Science.gov (United States)

    Watanabe, T A A; Cellucci, C J; Kohegyi, E; Bashore, T R; Josiassen, R C; Greenbaun, N N; Rapp, P E

    2003-01-01

    Symbolic measures of complexity provide a quantitative characterization of the sequential structure of symbol sequences. Promising results from the application of these methods to the analysis of electroencephalographic (EEG) and event-related brain potential (ERP) activity have been reported. Symbolic measures used thus far have two limitations, however. First, because the value of complexity increases with the length of the message, it is difficult to compare signals of different epoch lengths. Second, these symbolic measures do not generalize easily to the multichannel case. We address these issues in studies in which both single and multichannel EEGs were analyzed using measures of signal complexity and algorithmic redundancy, the latter being defined as a sequence-sensitive generalization of Shannon's redundancy. Using a binary partition of EEG activity about the median, redundancy was shown to be insensitive to the size of the data set while being sensitive to changes in the subject's behavioral state (eyes open vs. eyes closed). The covariance complexity, calculated from the singular value spectrum of a multichannel signal, was also found to be sensitive to changes in behavioral state. Statistical separations between the eyes open and eyes closed conditions were found to decrease following removal of the 8- to 12-Hz content in the EEG, but still remained statistically significant. Use of symbolic measures in multivariate signal classification is described.

  2. Adolescent mice are more vulnerable than adults to single injection-induced behavioral sensitization to amphetamine.

    Science.gov (United States)

    Kameda, Sonia R; Fukushiro, Daniela F; Trombin, Thaís F; Procópio-Souza, Roberta; Patti, Camilla L; Hollais, André W; Calzavara, Mariana B; Abílio, Vanessa C; Ribeiro, Rosana A; Tufik, Sergio; D'Almeida, Vânia; Frussa-Filho, Roberto

    2011-04-01

    Drug-induced behavioral sensitization in rodents has enhanced our understanding of why drugs acquire increasing motivational and incentive value. Compared to adults, human adolescents have accelerated dependence courses with shorter times from first exposure to dependence. We compared adolescent and adult mice in their ability to develop behavioral sensitization to amphetamine following a single injection. Adult (90-day-old) and adolescent (45-day-old) male Swiss mice received an acute intraperitoneal injection of saline or amphetamine (1.0, 2.0 or 4.0 mg/kg). Seven days later, half of the mice from the saline group received a second injection of saline. The remaining animals were challenged with 2.0 mg/kg amphetamine. Following all of the injections, mice were placed in activity chambers and locomotion was quantified for 45 min. The magnitude of both the acute and sensitized locomotor stimulatory effect of amphetamine was higher in the adolescent mice. Previous experience with the test environment inhibited the acute amphetamine stimulation in both adolescent and adult mice, but facilitated the detection of elevated spontaneous locomotion in adolescent animals. These results support the notion that the adolescent period is associated with an increased risk for development of drug abuse. Additionally, they indicate a complex interaction between the environmental novelty, adolescence and amphetamine.

  3. Evaluating Emotional and Biological Sensitivity to Maternal Behavior Among Self-Injuring and Depressed Adolescent Girls Using Nonlinear Dynamics

    DEFF Research Database (Denmark)

    Crowe, Sheila E; Butner, Jonathan E.; Wiltshire, Travis

    2017-01-01

    High sensitivity and reactivity to behaviors of family members characterize several forms of psychopathology, including self-inflicted injury (SII). We examined mother-daughter behavioral and psychophysiological reactivity during a conflict discussion using nonlinear dynamics to assess asymmetrical...... would not evoke mothers’ behavioral or physiological reactivity, and (c) control teens and mothers would be less reactive, with no dynamic associations in either direction. Convergent cross-mapping with dewdrop regression, which identifies directional associations, indicated that mothers’ behaviors...

  4. Tramadol—induced physical dependence and its effects on behavioral sensitization to methamphetamine in mice

    Institute of Scientific and Technical Information of China (English)

    LiangJH; WangK

    2002-01-01

    Tramadol is a widely used and non-controlled analgesic,which stimulates both centrally opiatergic and monoaminergic systems.The epidemiological data indicate that tramadol possesses relatively high poly-drug abuse potential.Therefore,the present study was designed to assess the physical dependence of tramadol and investigate the effects of tramadol on behavioral sensitization to methamphetamine (MA) and its toxicity.Mice were made acute dependence on tramadol by injection (sc) of tramadol.After 3h,naloxone was given (ip) to precipitate withdrawal symptoms.The results showed that tramadol displayed marked naloxoneprecipitated withdrawal symptoms.5-HTP,a precursor of 5-HT,attenuated tramadol withdrawal symptoms,but parachlorophenylalanine,a tryptophan hydroxylase inhibitor,aggravated them.In the open field test,tramadol enhanced the development and expression of behavioral sensitization to MA in mice.In addition,co-administration of tramadol (120mg·kg-1,a non-lethal dose) and MA reduced the LD50 for MA from 63.4mg·kg-1 to 32.3mg·kg-1.Our findings suggest that tramadol produce physical dependence in itself and potentiate MA-induced addictive behavior and toxicity.

  5. A comparison of survey techniques on sensitive sexual behavior in Italy.

    Science.gov (United States)

    Caltabiano, Marcantonio; Dalla-Zuanna, Gianpiero

    2013-01-01

    This article compares two national surveys carried out through the most commonly used procedures in Italy: CATI (computer-assisted telephone interviews) and SAQ-FI (self-answered questionnaires following interviews). Both surveys ask two identical questions concerning sensitive sexual behavior: early age at first intercourse and same-sex attraction. The SAQ-FI survey had both unit non-response and item non-response rates much lower than the CATI survey. Moreover, in the CATI survey, the groups with highest item non-response rates were also the groups with the lowest proportions of early intercourse and homosexual attraction. In addition, a differential analysis of the respondents produced diverse results for the two surveys. This is especially true of results by gender for same-sex attraction: Such behavior is more common among men (3.1%) than women (2.9%), according to the CATI survey, whereas the opposite is true of the SAQ-FI survey (6.1% of men vs. 7.7% women). In Italy at the beginning of the 21st century, CATI surveys reveal a lower level of early intercourse and same-sex attraction than SAQ-FI surveys. This article argues that the CATI survey underestimates the true level of these sensitive sexual behaviors in the Italian population.

  6. Sensitivity studies on thermal-hydraulic behavior associated with LOFT total loss-of-feedwater accident

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K.B.; Lee, H.; Ko, H.J.; Seong, H.J.; Jeung, J.S. [Department of Nuclar Engineering, Korea Power Engineering Company, Inc., Gyeonggi-do (Korea, Republic of); Chang, H.K. [Seoul National University, Seoul (Korea, Republic of)

    2004-07-01

    The purpose of this paper is to study the thermal-hydraulic behaviors associated with the Loss-of-Fluid Test (LOFT) Experiment of total loss-of-feedwater accident and its recovery (Test No. L9-1/L3-3), and to perform sensitivity studies to identify parameters having significant effect on the thermal-hydraulic behaviors predicted by RELAP5/MOD3.3-Beta computer code. The Experiment L9-1/L3-3 was a simulation of the total loss-of-feedwater (TLOFW) accident and its recovery modes. Generally, the RELAP5/MOD3.3Beta calculation results were in good agreement with experimental data, even though some differences were also observed. Sensitivity studies showed that several parameters have significant effect on the predicted thermal-hydraulic behaviors. These parameters include the pressurizer spray system loss coefficient, nodalization of the steam generator secondary side, steam generator U-tube heat transfer area, heat transfer coefficient from the LOFT main components to the environment, and the power-operated relief valve (PORV) discharge coefficient. The first three parameters are significant during the short-term transient phase, while the last two are significant during the long-term transient phase. Therefore, the five parameters should be carefully modeled to obtain appropriate calculation results for transient types such as the total-loss-of feedwater accident and its recovery modes. (authors)

  7. Uncertainty and sensitivity analysis of fission gas behavior in engineering-scale fuel modeling

    Energy Technology Data Exchange (ETDEWEB)

    Pastore, Giovanni, E-mail: Giovanni.Pastore@inl.gov [Fuel Modeling and Simulation, Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415-3840 (United States); Swiler, L.P., E-mail: LPSwile@sandia.gov [Optimization and Uncertainty Quantification, Sandia National Laboratories, P.O. Box 5800, Albuquerque, NM 87185-1318 (United States); Hales, J.D., E-mail: Jason.Hales@inl.gov [Fuel Modeling and Simulation, Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415-3840 (United States); Novascone, S.R., E-mail: Stephen.Novascone@inl.gov [Fuel Modeling and Simulation, Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415-3840 (United States); Perez, D.M., E-mail: Danielle.Perez@inl.gov [Fuel Modeling and Simulation, Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415-3840 (United States); Spencer, B.W., E-mail: Benjamin.Spencer@inl.gov [Fuel Modeling and Simulation, Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415-3840 (United States); Luzzi, L., E-mail: Lelio.Luzzi@polimi.it [Politecnico di Milano, Department of Energy, Nuclear Engineering Division, via La Masa 34, I-20156 Milano (Italy); Van Uffelen, P., E-mail: Paul.Van-Uffelen@ec.europa.eu [European Commission, Joint Research Centre, Institute for Transuranium Elements, Hermann-von-Helmholtz-Platz 1, D-76344 Karlsruhe (Germany); Williamson, R.L., E-mail: Richard.Williamson@inl.gov [Fuel Modeling and Simulation, Idaho National Laboratory, P.O. Box 1625, Idaho Falls, ID 83415-3840 (United States)

    2015-01-15

    The role of uncertainties in fission gas behavior calculations as part of engineering-scale nuclear fuel modeling is investigated using the BISON fuel performance code with a recently implemented physics-based model for fission gas release and swelling. Through the integration of BISON with the DAKOTA software, a sensitivity analysis of the results to selected model parameters is carried out based on UO{sub 2} single-pellet simulations covering different power regimes. The parameters are varied within ranges representative of the relative uncertainties and consistent with the information in the open literature. The study leads to an initial quantitative assessment of the uncertainty in fission gas behavior predictions with the parameter characterization presently available. Also, the relative importance of the single parameters is evaluated. Moreover, a sensitivity analysis is carried out based on simulations of a fuel rod irradiation experiment, pointing out a significant impact of the considered uncertainties on the calculated fission gas release and cladding diametral strain. The results of the study indicate that the commonly accepted deviation between calculated and measured fission gas release by a factor of 2 approximately corresponds to the inherent modeling uncertainty at high fission gas release. Nevertheless, significantly higher deviations may be expected for values around 10% and lower. Implications are discussed in terms of directions of research for the improved modeling of fission gas behavior for engineering purposes.

  8. Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice.

    Science.gov (United States)

    Oliveira-Lima, A J; Santos, R; Hollais, A W; Gerardi-Junior, C A; Baldaia, M A; Wuo-Silva, R; Yokoyama, T S; Costa, J L; Malpezzi-Marinho, E L A; Ribeiro-Barbosa, P C; Berro, L F; Frussa-Filho, R; Marinho, E A V

    2015-04-01

    Hallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems. We investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8g/kg) for 8 alternate days. Aya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500 mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500 mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300 mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge. We demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The effect of varenicline on the development and expression of nicotine-induced behavioral sensitization and cross-sensitization in rats.

    Science.gov (United States)

    Goutier, Wouter; Kloeze, Margreet B; McCreary, Andrew C

    2015-03-01

    The present study focused on the evaluation of behavioral sensitization and cross-sensitization induced by nicotine and varenicline in rats. Furthermore, it examined the influence of varenicline, a partial alpha4beta2 nicotinic receptor agonist, on nicotine-induced sensitization. To assess the development of behavioral sensitization, rats were chronically treated with vehicle, varenicline (0.03-3.0 mg/kg), nicotine (0.4 mg/kg) or combinations for 5 days and locomotor activity was measured. The expression of sensitization was assessed following a withdrawal period (17-26 days). The present results confirmed previous data showing the development and expression of nicotine-induced sensitization of locomotor activity in the rat. Varenicline did not induce sensitization on its own. When varenicline and nicotine were repeatedly administered sequentially, varenicline blocked the development and expression of nicotine-induced sensitization. Acute varenicline blocked the expression of nicotine-induced sensitization in a dose-dependent manner. Acute varenicline did not significantly increase locomotor activity, nor did it attenuate nicotine-induced sensitization. However, varenicline did cross-sensitize to the effects of nicotine, and vice versa. The present study showed that varenicline produced a dose-dependent bidirectional cross-sensitization with nicotine. Taken together, these findings provide pre-clinical evidence that varenicline is able to attenuate the effects of nicotine, yet simultaneously 'substitutes' for the effects of nicotine in the rat. Longitudinal studies would be needed to see if similar effects are seen in the clinical setting, and whether such effects contribute to the actions of varenicline as a smoking cessation aid.

  10. Sensitive periods in epigenetics: bringing us closer to complex behavioral phenotypes.

    Science.gov (United States)

    Nagy, Corina; Turecki, Gustavo

    2012-08-01

    Genetic studies have attempted to elucidate causal mechanisms for the development of complex disease, but genome-wide associations have been largely unsuccessful in establishing these links. As an alternative link between genes and disease, recent efforts have focused on mechanisms that alter the function of genes without altering the underlying DNA sequence. Known as epigenetic mechanisms, these include DNA methylation, chromatin conformational changes through histone modifications, ncRNAs and, most recently, 5-hydroxymethylcytosine. Although DNA methylation is involved in normal development, aging and gene regulation, altered methylation patterns have been associated with disease. It is generally believed that early life constitutes a period during which there is increased sensitivity to the regulatory effects of epigenetic mechanisms. The purpose of this review is to outline the contribution of epigenetic mechanisms to genomic function, particularly in the development of complex behavioral phenotypes, focusing on the sensitive periods.

  11. Sensitive Periods in Epigenetics: bringing us closer to complex behavioral phenotypes

    Science.gov (United States)

    Nagy, Corina; Turecki, Gustavo

    2017-01-01

    Genetic studies have attempted to elucidate causal mechanisms for the development of complex disease but genome-wide associations have been largely unsuccessful in establishing these links. As an alternative link between genes and disease, recent efforts have focused on mechanisms that alter the function of genes without altering the underlying DNA sequence. Known as epigenetic mechanisms, these include: DNA methylation, chromatin conformational changes through histone modifications, non-coding RNAs, and most recently, 5-hydroxymethylcytosine. Though DNA methylation is involved in normal development, aging and gene regulation, altered methylation patterns have been associated with disease. It is generally believed that early life constitutes a period during which there is increased sensitivity to the regulatory effects of epigenetic mechanisms. The purpose of this review is to outline the contribution of epigenetic mechanisms to genomic function, particularly in the development of complex behavioral phenotypes, focusing on the sensitive periods. PMID:22920183

  12. Corrosion Behavior of the Stressed Sensitized Austenitic Stainless Steels of High Nitrogen Content in Seawater

    Directory of Open Access Journals (Sweden)

    A. Almubarak

    2013-01-01

    Full Text Available The purpose of this paper is to study the effect of high nitrogen content on corrosion behavior of austenitic stainless steels in seawater under severe conditions such as tensile stresses and existence of sensitization in the structure. A constant tensile stress has been applied to sensitized specimens types 304, 316L, 304LN, 304NH, and 316NH stainless steels. Microstructure investigation revealed various degrees of stress corrosion cracking. SCC was severe in type 304, moderate in types 316L and 304LN, and very slight in types 304NH and 316NH. The electrochemical polarization curves showed an obvious second current peak for the sensitized alloys which indicated the existence of second phase in the structure and the presence of intergranular stress corrosion cracking. EPR test provided a rapid and efficient nondestructive testing method for showing passivity, degree of sensitization and determining IGSCC for stainless steels in seawater. A significant conclusion was obtained that austenitic stainless steels of high nitrogen content corrode at a much slower rate increase pitting resistance and offer an excellent resistance to stress corrosion cracking in seawater.

  13. The effects of instructions on the sensitivity of negatively reinforced human behavior to extinction.

    Science.gov (United States)

    Alessandri, Jérôme; Cançado, Carlos R X

    2017-03-01

    The effects of instructions on the sensitivity of negatively reinforced (escape) behavior to extinction were studied. Initially, responding produced timeouts from pressing a force cell on a variable-ratio (VR) schedule, which was then discontinued (extinction). Based on extinction data, participants were distributed into two groups. Participants in the Extinction Group (for which response rates were low in extinction) were instructed that the experimenter expected them to continue responding in extinction after a second exposure to the VR schedule. Participants in the Persistence group (for which response rates were high in extinction) were instructed that the experimenter expected them to stop responding in extinction. Relative to the condition in which instructions were absent, extinction-response rates increased and decreased, respectively, for participants in the Persistence and Extinction groups. These results replicate and extend to negatively reinforced responding previous findings that showed behavioral control by instructions formulated as explicit experimenter demands or expectations.

  14. A Molecular Thermodynamic Model for Restricted Swelling Behaviors of Thermo-sensitive Hydrogel☆

    Institute of Scientific and Technical Information of China (English)

    Cheng Lian; Dongyan Zhi; Shouhong Xu; Honglai Liu

    2014-01-01

    A molecular thermodynamic model was developed for describing the restricted swelling behavior of a thermo-sensitive hydrogel confined in a limited space. The Gibbs free energy includes two contributions, the contribution of mixing of polymer and solvent calculated by using the lattice model of random polymer solution, and the con-tribution due to the elasticity of polymer network. This model can accurately describe the swel ing behavior of restricted hydrogels under uniaxial and biaxial constraints by using two model parameters. One is the interaction energy parameter between polymer network and solvent, and the other is the size parameter depending on the degree of cross-linking. The calculated results show that the swelling ratio reduces significantly and the phase transition temperature decreases slightly as the restricted degree increases, which agree wel with the experi-mental data.

  15. Diacylglycerol kinase β knockout mice exhibit lithium-sensitive behavioral abnormalities.

    Directory of Open Access Journals (Sweden)

    Kenichi Kakefuda

    Full Text Available BACKGROUND: Diacylglycerol kinase (DGK is an enzyme that phosphorylates diacylglycerol (DG to produce phosphatidic acid (PA. DGKβ is widely distributed in the central nervous system, such as the olfactory bulb, cerebral cortex, striatum, and hippocampus. Recent studies reported that the splice variant at the COOH-terminal of DGKβ was related to bipolar disorder, but its detailed mechanism is still unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we performed behavioral tests using DGKβ knockout (KO mice to investigate the effects of DGKβ deficits on psychomotor behavior. DGKβ KO mice exhibited some behavioral abnormalities, such as hyperactivity, reduced anxiety, and reduced depression. Additionally, hyperactivity and reduced anxiety were attenuated by the administration of the mood stabilizer, lithium, but not haloperidol, diazepam, or imipramine. Moreover, DGKβ KO mice showed impairment in Akt-glycogen synthesis kinase (GSK 3β signaling and cortical spine formation. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKβ KO mice exhibit lithium-sensitive behavioral abnormalities that are, at least in part, due to the impairment of Akt-GSK3β signaling and cortical spine formation.

  16. Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil

    OpenAIRE

    Wuo-Silva, Raphael; Fukushiro, Daniela F.; Hollais, André W.; Santos-Baldaia, Renan; Mári-Kawamoto, Elisa; Berro, Laís F.; Yokoyama, Thaís S.; Lopes-Silva, Leonardo B.; Bizerra, Carolina S.; Procópio-Souza, Roberta; Hashiguchi, Debora; Figueiredo, Lilian A.; Jose L. Costa; Frussa-Filho, Roberto; Longo, Beatriz M.

    2016-01-01

    There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of dru...

  17. The role of L-type calcium channels in the development and expression of behavioral sensitization to ethanol.

    Science.gov (United States)

    Broadbent, Julie

    2013-10-11

    Behavioral sensitization is thought to play a significant role in drug addiction. L-type calcium channels have been implicated in sensitization to stimulant and opiate drugs but it is unclear if these channels also contribute to sensitization to ethanol. The effects of three L-type calcium channel blockers, nifedipine (1-7.5 mg/kg), diltiazem (12.5-50 mg/kg), and verapamil (12.5 and 25 mg/kg), on sensitization to ethanol (2 g/kg) were examined in DBA/2J mice. All three blockers reduced but did not prevent expression of sensitization. Only nifedipine blocked acquisition of sensitization. Nifedipine and verapamil decreased blood ethanol levels. The current findings suggest L-type calcium channels do not play a substantial role in sensitization to ethanol and that the neural mechanisms underlying sensitization to ethanol are distinct from those mediating sensitization to stimulants and opiates.

  18. Behavioral sensitization produced by a single administration of apomorphine: implications for the role of Pavlovian conditioning in the mediation of context-specific sensitization.

    Science.gov (United States)

    Bloise, Enrrico; Carey, Robert J; Carrera, Marinete Pinheiro

    2007-03-01

    The present study examined the minimal number of exposures to the D1/D2 agonist apomorphine capable of producing behavioral sensitization. Rats received one (experiment 1) or two administrations on two successive days (experiment 2) of apomorphine (0.5 and 2.0 mg/kg) paired or unpaired to an open-field environment. After 2 days of drug withdrawal, the rats received a challenge injection with the same dose of apomorphine (sensitization test) and locomotion, rearing and sniffing were measured. The results of the first experiment showed that locomotor sensitization occurred after a single acute exposure to apomorphine and that 0.5 and 2.0 mg/kg treatments were equally effective. This sensitization effect was context-specific and was limited to locomotion. The second experiment revealed a differential dose effect on the sensitization test. Two treatments with 2.0 mg/kg potentiated locomotor sensitization as compared with a single treatment but two treatments with 0.5 mg/kg did not increase the sensitization effect more than the single 0.5 mg/kg treatment. This result indicates an interaction between drug dose and frequency of drug treatment for the induction of apomorphine locomotor sensitization. In that the sensitization effects are considered to be a core contributor to psychostimulant addiction, the present findings are of importance to understanding addiction because they indicate that sensitization processes can be initiated with a single drug experience and amplified with exposure to higher drug dosage levels.

  19. Effects of disclosing hypothetical genetic test results for salt sensitivity on salt restriction behavior

    Directory of Open Access Journals (Sweden)

    Takeshima T

    2013-05-01

    Full Text Available Taro Takeshima,1,2 Masanobu Okayama,1 Masanori Harada,3 Ryusuke Ae,4 Eiji Kajii1 1Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Tochigi, Japan; 2Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan; 3Department for Support of Rural Medicine, Yamaguchi Grand Medical Center, Yamaguchi, Japan; 4Department of General Internal Medicine, Hamasaka Public Hospital, Mikata, Japan Background: A few studies have explored the effects of disclosure of genetic testing results on chronic disease predisposition. However, these effects remain unclear in cases of hypertension. Reducing salt intake is an important nonpharmacological intervention for hypertension. We investigated the effects of genetic testing for salt sensitivity on salt restriction behavior using hypothetical genetic testing results. Methods: We conducted a cross-sectional study using a self-completed questionnaire. We enrolled consecutive outpatients who visited primary care clinics and small hospitals between September and December 2009 in Japan. We recorded the patients’ baseline characteristics and data regarding their salt restriction behavior, defined as reducing salt intake before and after disclosure of hypothetical salt sensitivity genetic test results. Behavioral stage was assessed according to the five-stage transtheoretical model. After dividing subjects into salt restriction and no salt restriction groups, we compared their behavioral changes following positive and negative test results and analyzed the association between the respondents’ characteristics and their behavioral changes. Results: We analyzed 1562 participants with a mean age of 58 years. In the no salt restriction group, which included patients at the precontemplation, contemplation, and preparation stages, 58.7% stated that their behavioral stage progressed after a positive test result, although 29

  20. Whole body vibration induces forepaw and hind paw behavioral sensitivity in the rat.

    Science.gov (United States)

    Baig, Hassam A; Guarino, Benjamin B; Lipschutz, Daniel; Winkelstein, Beth A

    2013-11-01

    Whole body vibration (WBV) has been linked to neck and back pain, but the biomechanical and physiological mechanisms responsible for its development and maintenance are unknown. A rodent model of WBV was developed in which rats were exposed to different WBV paradigms, either daily for 7 consecutive days (repeated WBV) or two single exposures at Day 0 and 7 (intermittent WBV). Each WBV session lasted for 30 min and was imposed at a frequency of 15 Hz and RMS platform acceleration of 0.56 ± 0.07 g. Changes in the withdrawal response of the forepaw and hind paw were measured, and were used to characterize the onset and maintenance of behavioral sensitivity. Accelerations and displacements of the rat and deformations in the cervical and lumbar spines were measured during WBV to provide mechanical context for the exposures. A decrease in withdrawal threshold was induced at 1 day after the first exposure in both the hind paw and forepaw. Repeated WBV exhibited a sustained reduction in withdrawal threshold in both paws and intermittent WBV induced a sustained response only in the forepaw. Cervical deformations were significantly elevated which may explain the more robust forepaw response. Findings suggest that a WBV exposure leads to behavioral sensitivity.

  1. Adolescent behavioral and neural reward sensitivity: a test of the differential susceptibility theory

    Science.gov (United States)

    Richards, J S; Arias Vásquez, A; von Rhein, D; van der Meer, D; Franke, B; Hoekstra, P J; Heslenfeld, D J; Oosterlaan, J; Faraone, S V; Buitelaar, J K; Hartman, C A

    2016-01-01

    Little is known about the causes of individual differences in reward sensitivity. We investigated gene–environment interactions (GxE) on behavioral and neural measures of reward sensitivity, in light of the differential susceptibility theory. This theory states that individuals carrying plasticity gene variants will be more disadvantaged in negative, but more advantaged in positive environments. Reward responses were assessed during a monetary incentive delay task in 178 participants with and 265 without attention-deficit/hyperactivity disorder (ADHD), from N=261 families. We examined interactions between variants in candidate plasticity genes (DAT1, 5-HTT and DRD4) and social environments (maternal expressed emotion and peer affiliation). HTTLPR short allele carriers showed the least reward speeding when exposed to high positive peer affiliation, but the most when faced with low positive peer affiliation or low maternal warmth. DAT1 10-repeat homozygotes displayed similar GxE patterns toward maternal warmth on general task performance. At the neural level, DRD4 7-repeat carriers showed the least striatal activation during reward anticipation when exposed to high maternal warmth, but the most when exposed to low warmth. Findings were independent of ADHD severity. Our results partially confirm the differential susceptibility theory and indicate the importance of positive social environments in reward sensitivity and general task performance for persons with specific genotypes. PMID:27045841

  2. Reward/punishment sensitivities among internet addicts: Implications for their addictive behaviors.

    Science.gov (United States)

    Dong, Guangheng; Hu, Yanbo; Lin, Xiao

    2013-10-01

    Internet addiction disorder (IAD) has raised widespread public health concerns. In this study, we used a gambling task to simulate extreme win/lose situations to find the reward/punishment sensitivities after continuous wins and losses. FMRI data were collected from 16 IAD subjects (21.4±3.1years) and 15 healthy controls (HC, 22.1±3.6years). Group comparisons showed higher superior frontal gyrus activations after continuous wins for IAD subjects than for HC. The brain activities in IAD subjects were not disturbed by their losses. In addition, IAD participants showed decreased posterior cingulate activation compared to HC after continuous losses. These results indicated that IAD participants showed preference to win while neglecting their losses. Therefore they engaged less executive endeavor to control their frustration after continuous losses. Taken together, we concluded that IAD subjects showed enhanced sensitivity to win and decreased sensitivity to lose. This can help us understand why IAD subjects continue playing online even after noticing the severe negative consequences of their behaviors.

  3. Different Fear-Regulation Behaviors in Toddlerhood: Relations to Preceding Infant Negative Emotionality, Maternal Depression, and Sensitivity

    Science.gov (United States)

    Gloggler, Bettina; Pauli-Pott, Ursula

    2008-01-01

    In the study presented, the development of different fear regulation behaviors and their associations with preceding maternal sensitivity and depression is addressed. A sample of 64 mother-child pairs was examined at the children's ages of 4, 12, and 30 months. Four-month negative reactivity and 12- and 30- month behavioral inhibition and fear…

  4. Theory of Planned Behavior: Sensitivity and Specificity in Predicting Graduation and Drop-Out among College and University Students?

    Science.gov (United States)

    Fichten, Catherine S.; Amsel, Rhonda; Jorgensen, Mary; Nguyen, Mai Nhu; Budd, Jillian; King, Laura; Jorgensen, Shirley; Asuncion, Jennison

    2016-01-01

    We examined sensitivity and specificity when using the three theory of planned behavior (TPB) scales (Perceived Behavioral Control, Subjective Norms, Attitude) to predict graduation and drop-out in a longitudinal study of 252 college and university students with disabilities and in a separate cross-sectional study of a random sample of 1380…

  5. Sensitivity of Gray’s behavioral inhibition system in clinically anxious and non-anxious children and adolescents

    NARCIS (Netherlands)

    Vervoort, L.; Wolters, L.H.; Hogendoorn, S.M.; de Haan, E.; de Boer, F.; Prins, P.J.M.

    2010-01-01

    The child version of the Carver and White (1994) BIS/BAS-scales (Muris et al., 2005) was used to assess sensitivity of the Behavioral Inhibition and the Behavioral Activation System in clinically anxious and non-anxious youth (n = 175, ages 8-18 years, 70 boys). Results supported the hypothesis that

  6. Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil.

    Science.gov (United States)

    Wuo-Silva, Raphael; Fukushiro, Daniela F; Hollais, André W; Santos-Baldaia, Renan; Mári-Kawamoto, Elisa; Berro, Laís F; Yokoyama, Thaís S; Lopes-Silva, Leonardo B; Bizerra, Carolina S; Procópio-Souza, Roberta; Hashiguchi, Debora; Figueiredo, Lilian A; Costa, Jose L; Frussa-Filho, Roberto; Longo, Beatriz M

    2016-01-01

    There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross-sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.

  7. Maternal mind-mindedness during infancy, general parenting sensitivity and observed child feeding behavior: a longitudinal study.

    Science.gov (United States)

    Farrow, Claire; Blissett, Jackie

    2014-01-01

    Maternal mind-mindedness, or the tendency to view the child as a mental agent, has been shown to predict sensitive and responsive parenting behavior. As yet the role of mind-mindedness has not been explored in the context of feeding interactions. This study evaluates the relations between maternal mind-mindedness at 6 months of infant age and subsequently observed maternal sensitivity and feeding behaviors with children at age 1 year. Maternal mind-mindedness was greater in mothers who had breast-fed compared to formula-fed. Controlling for breast-feeding, mind-mindedness at 6 months was correlated with observations of more sensitive and positive feeding behaviors at 1 year of age. Mind-mindedness was also associated with greater general maternal sensitivity in play and this general parenting sensitivity mediated the effect of mind-mindedness on more sensitive and positive feeding behaviors. Interventions to promote maternal tendency to consider their child's mental states may encourage more adaptive parental feeding behaviors.

  8. An Equation-of-State Compositional In-Situ Combustion Model: A Study of Phase Behavior Sensitivity

    DEFF Research Database (Denmark)

    Kristensen, Morten Rode; Gerritsen, M. G.; Thomsen, Per Grove

    2009-01-01

    of in situ combustion processes is the formation and sustained propagation of a high-temperature combustion front. Using the models developed, we study the impact of phase behavior on ignition/extinction dynamics as a function of the operating conditions. We show that when operating close to ignition/extinction...... branches, a change of phase behavior model will shift the system from a state of ignition to a state of extinction or vice versa. For both the rigorous equation of state based and a simplified, but commonly used, K-value-based phase behavior description we identify areas of operating conditions which lead...... phase behavior sensitivity for in situ combustion, a thermal oil recovery process. For the one-dimensional model we first study the sensitivity to numerical discretization errors and provide grid density guidelines for proper resolution of in situ combustion behavior. A critical condition for success...

  9. Perinatal protein deprivation facilitates morphine cross-sensitization to cocaine and enhances ΔFosB expression in adult rats.

    Science.gov (United States)

    Perondi, María Cecilia; Gutiérrez, María Cecilia; Valdomero, Analía; Cuadra, Gabriel Ricardo

    2017-08-30

    Previous studies have indicated that neural changes induced by early nutritional insult cause an altered response to pharmacological treatments, including addictive drugs. This study evaluates the influence of perinatal protein malnutrition in developing cross-sensitization to cocaine-induced rewarding effects in animals pre-exposed to morphine. Different groups of well-nourished (C-rats) and protein-deprived animals (D-rats) were treated twice a day for three days with increasing doses of morphine or with saline. After 3days, the incentive motivational effects of cocaine were assessed in a Conditioned Place Preference paradigm in both groups. In saline pre-treated animals, dose-response curves to cocaine revealed a conditioning effect in D-rats at doses of 5, 7.5 and 10mg/kg, while this effect was observed in C-rats only with 10 and 15mg/kg. Furthermore, when animals of both groups were pre-treated with escalating doses of morphine, cross-sensitization to the conditioning effect of cocaine was elicited only in D-rats with low doses of cocaine (5 and 7.5mg/kg). In contrast, under the same experimental conditions, C-rats show no cross-sensitization. To correlate this differential rewarding response with a molecular substrate linked to the behavioral changes observed after repeated drug exposure, ΔFosB expression was assessed in different brain regions. D-rats showed a significant increase in this transcription factor in the nucleus accumbens, amygdala and medial prefrontal cortex. These results demonstrated that perinatal protein deprivation facilitates rewarding effects and the development of cross-sensitization to cocaine, which correlates with an upregulation of ΔFosB in brain areas related to the reward circuitry. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Precipitation Behavior and Quenching Sensitivity of a Spray Deposited Al-Zn-Mg-Cu-Zr Alloy

    Directory of Open Access Journals (Sweden)

    Xiaofei Sheng

    2017-09-01

    Full Text Available Precipitation behavior and the quenching sensitivity of a spray deposited Al-Zn-Mg-Cu-Zr alloy during isothermal heat treatment have been studied systematically. Results demonstrate that both the hardness and the ultimate tensile strength of the studied alloy decreased with the isothermal treatment time at certain temperatures. More notably, the hardness decreases rapidly after the isothermal heat treatment. During isothermal heat treatment processing, precipitates readily nucleated in the medium-temperature zone (250–400 °C, while the precipitation nucleation was scarce in the low-temperature zone (<250 °C and in the high-temperature zone (>400 °C. Precipitates with sizes of less than ten nanometers would contribute a significant increase in yield strength, while the ones with a larger size than 300 nm would contribute little strengthening effect. Quenching sensitivity is high in the medium-temperature zone (250–400 °C, and corresponding time-temperature-property (TTP curves of the studied alloy have been established.

  11. pH-Sensitive surfactants from lysine: assessment of their cytotoxicity and environmental behavior.

    Science.gov (United States)

    Colomer, Aurora; Pinazo, Aurora; García, Maria Teresa; Mitjans, Montserrat; Vinardell, M Pilar; Infante, Maria Rosa; Martínez, Verónica; Pérez, Lourdes

    2012-04-10

    The toxicity and environmental behavior of new pH-sensitive surfactants from lysine are presented. Three different chemical structures are studied: surfactants with one amino acid and one alkyl chain, surfactants with two amino acids on the polar head and one alkyl chain, and gemini surfactants. The pH sensitivity of these compounds can be tuned by modifying their chemical structures. Cytotoxicity has been evaluated using erythrocytes and fibroblast cells. The toxic effects against these cells depend on the hydrophobicity of the molecules as well as their cationic charge density. The effect of hydrophobicity and cationic charge density on toxicity is different for each type of cells. For erythrocytes, the toxicity increases as hydrophobicity and charge density increases. Nevertheless, for fibroblasts cationic charge density affects cytotoxicity in the opposite way: the higher charge density, the lower the toxicity. The effect of the pH on hemolysis has been evaluated in detail. The aquatic toxicity was established using Daphnia magna . All surfactants yielded EC(50) values considerably higher than that reported for cationic surfactants based on quaternary ammonium groups. Finally, their biodegradability was evaluated using the CO(2) headspace test (ISO 14593). These lysine derivatives showed high levels of biodegradation under aerobic conditions and can be classified as "readily biodegradable compounds".

  12. Mechanical behavior of a fluid-sensitive material during liquid diffusion

    Science.gov (United States)

    Widiastuti, Indah; Sbarski, Igor; Masood, S. H.

    2014-05-01

    This paper described the analytical study that we performed in an attempt to understand the combined effect of liquid diffusion and temperature on the mechanical response of viscoelastic liquid-sensitive material. A constitutive equation for linear viscoelasticity, which includes the effect of liquid diffusion, is used to model the mechanical response of a fluid-sensitive polymer such as PLA-based bioplastic. The viscoelastic characteristics which represent material degradation due to liquid diffusion were expressed using a creep-based formulation represented by Burger's model. Creep experiment data were fitted to the Burgers model to provide a liquid content-dependent set of input data for subsequent time-dependent analysis. Further, analytical solutions for stresses and deformations were obtained from the corresponding elastic solution by applying the Correspondence Principle, using previously defined material characteristics. Spatial and time variations of stress and deformation were evaluated to give a precise description of the material behavior under hygroscopic conditions. We propose a stress concentration factor to take into account the liquid diffusion-induced stress that may result in a failure of an application. The results emphasize the importance of considering liquid diffusion and viscoelastic properties in the design of components using liquid-absorbable material.

  13. Behavior of plant plasma membranes under hydrostatic pressure as monitored by fluorescent environment-sensitive probes.

    Science.gov (United States)

    Roche, Yann; Klymchenko, Andrey S; Gerbeau-Pissot, Patricia; Gervais, Patrick; Mély, Yves; Simon-Plas, Françoise; Perrier-Cornet, Jean-Marie

    2010-08-01

    We monitored the behavior of plasma membrane (PM) isolated from tobacco cells (BY-2) under hydrostatic pressures up to 3.5kbar at 30 degrees C, by steady-state fluorescence spectroscopy using the newly introduced environment-sensitive probe F2N12S and also Laurdan and di-4-ANEPPDHQ. The consequences of sterol depletion by methyl-beta-cyclodextrin were also studied. We found that application of hydrostatic pressure led to a marked decrease of hydration as probed by F2N12S and to an increase of the generalized polarization excitation (GPex) of Laurdan. We observed that the hydration effect of sterol depletion was maximal between 1 and 1.5 kbar but was much less important at higher pressures (above 2 kbar) where both parameters reached a plateau value. The presence of a highly dehydrated gel state, insensitive to the sterol content, was thus proposed above 2.5 kbar. However, the F2N12S polarity parameter and the di-4-ANEPPDHQ intensity ratio showed strong effect on sterol depletion, even at very high pressures (2.5-3.5 kbar), and supported the ability of sterols to modify the electrostatic properties of membrane, notably its dipole potential, in a highly dehydrated gel phase. We thus suggested that BY-2 PM undergoes a complex phase behavior in response to the hydrostatic pressure and we also emphasized the role of phytosterols to regulate the effects of high hydrostatic pressure on plant PM.

  14. Acute Cocaine Induces Fast Activation of D1 Receptor and Progressive Deactivation of D2 Receptor Strial Neurons: In Vivo Optical Microprobe [Ca(superscript)2+]subscript)i Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Du, C.; Luo, Z.; Volkow, N.D.; Heintz, N.; Pan, Y.; Du, C.

    2011-09-14

    Cocaine induces fast dopamine increases in brain striatal regions, which are recognized to underlie its rewarding effects. Both dopamine D1 and D2 receptors are involved in cocaine's reward but the dynamic downstream consequences of cocaine effects in striatum are not fully understood. Here we used transgenic mice expressing EGFP under the control of either the D1 receptor (D1R) or the D2 receptor (D2R) gene and microprobe optical imaging to assess the dynamic changes in intracellular calcium ([Ca{sup 2+}]{sub i} ) responses (used as marker of neuronal activation) to acute cocaine in vivo separately for D1R- versus D2R-expressing neurons in striatum. Acute cocaine (8 mg/kg, i.p.) rapidly increased [Ca{sup 2+}]{sub i} in D1R-expressing neurons (10.6 {+-} 3.2%) in striatum within 8.3 {+-} 2.3 min after cocaine administration after which the increases plateaued; these fast [Ca{sup 2+}]{sub i} increases were blocked by pretreatment with a D1R antagonist (SCH23390). In contrast, cocaine induced progressive decreases in [Ca{sup 2+}]{sub i} in D2R-expressing neurons (10.4 {+-} 5.8%) continuously throughout the 30 min that followed cocaine administration; these slower [Ca{sup 2+}]{sub i} decreases were blocked by pretreatment with a D2R antagonist (raclopride). Since activation of striatal D1R-expressing neurons (direct-pathway) enhances cocaine reward, whereas activation of D2R expressing neurons suppresses it (indirect-pathway) (Lobo et al., 2010), this suggests that cocaine's rewarding effects entail both its fast stimulation ofD1R (resulting in abrupt activation of direct-pathway neurons) and a slower stimulation of D2R (resulting in longer-lasting deactivation of indirect-pathway neurons). We also provide direct in vivo evidence of D2R and D1R interactions in the striatal responses to acute cocaine administration.

  15. Global state measures of the dentate gyrus gene expression system predict antidepressant-sensitive behaviors.

    Directory of Open Access Journals (Sweden)

    Benjamin A Samuels

    Full Text Available BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs such as fluoxetine are the most common form of medication treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems respond to treatments may be critical for understanding antidepressant resistance. METHODS: We take a novel approach to this problem by demonstrating that the gene expression system of the dentate gyrus responds to fluoxetine (FLX, a commonly used antidepressant medication, in a stereotyped-manner involving changes in the expression levels of thousands of genes. The aggregate behavior of this large-scale systemic response was quantified with principal components analysis (PCA yielding a single quantitative measure of the global gene expression system state. RESULTS: Quantitative measures of system state were highly correlated with variability in levels of antidepressant-sensitive behaviors in a mouse model of depression treated with fluoxetine. Analysis of dorsal and ventral dentate samples in the same mice indicated that system state co-varied across these regions despite their reported functional differences. Aggregate measures of gene expression system state were very robust and remained unchanged when different microarray data processing algorithms were used and even when completely different sets of gene expression levels were used for their calculation. CONCLUSIONS: System state measures provide a robust method to quantify and relate global gene expression system state variability to behavior and treatment. State variability also suggests that the diversity of reported changes in gene expression levels in response to treatments such as fluoxetine may represent different perspectives on unified but noisy global gene expression system state level responses. Studying regulation of gene expression systems at the state level may be useful in guiding new

  16. Increased brain dopamine D4-like binding after chronic ethanol is not associated with behavioral sensitization in mice.

    Science.gov (United States)

    Quadros, Isabel Marian Hartmann; Nobrega, Jose Nascimento; Hipolide, Debora Cristina; Souza-Formigoni, Maria Lucia Oliveira

    2005-10-01

    Dopaminergic D4 receptors have been hypothesized to be involved in neuropsychiatric disorders and substance abuse. In mice, repeated ethanol administration may induce behavioral sensitization, a phenomenon of increased sensitivity to the drug's stimulant properties. This study aimed to analyze brain D4 receptors binding in mice with different levels of behavioral sensitization to ethanol. Male Swiss mice received 2.2 g/kg ethanol (n = 64) or saline (n = 16) intraperitoneally daily for 21 days and were weekly tested for locomotor activity and for blood ethanol levels. According to the locomotor scores presented across test days, ethanol-treated mice were classified as "sensitized" or "nonsensitized." Twenty-four hours after the last administration, mice were sacrificed and brains were processed for autoradiography. Brain D4 binding was assessed by quantitative autoradiography using [3H]nemonapride + raclopride in three groups: saline-treated controls (n = 10), ethanol-sensitized (n = 11), and ethanol-nonsensitized (n = 9) mice. Both sensitized and nonsensitized mice showed higher D4 binding densities than saline-treated controls in the posterior caudate-putamen and the olfactory tubercle (p < .02), but only sensitized mice presented higher D4 binding than controls at the lateral septal nucleus (p < .02). However, there were no differences between sensitized and nonsensitized mice in any of the brain regions analyzed. Furthermore, sensitized and nonsensitized mice presented similar blood ethanol levels during the treatment. The higher D4 binding levels observed in both ethanol-treated subgroups (sensitized and nonsensitized) suggest that chronic ethanol treatment may induce upregulation of D4 receptors in specific brain regions. However, this mechanism does not seem to be associated with the differential ability to develop behavioral sensitization to ethanol in mice.

  17. Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses

    Science.gov (United States)

    Pildervasser, João V. N.; Abrahao, Karina P.; Souza-Formigoni, Maria L. O.

    2014-01-01

    Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties. PMID:25152719

  18. Sleep Fragmentation Exacerbates Mechanical Hypersensitivity and Alters Subsequent Sleep-Wake Behavior in a Mouse Model of Musculoskeletal Sensitization

    Science.gov (United States)

    Sutton, Blair C.; Opp, Mark R.

    2014-01-01

    Study Objectives: Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Results: Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on

  19. The importance of sensitive parenting : a longitudinal adoption study on maternal sensitivity, problem behavior, and cortisol secretion

    NARCIS (Netherlands)

    Voort, Anja van der

    2014-01-01

    The current thesis focuses on the longitudinal development of early-adopted children in the Leiden Longitudinal Adoption Study (LLAS). In the LLAS, adopted children were followed from infancy until young adulthood. In Chapter 1 we discuss the role of sensitive parenting and the precursors and develo

  20. Naltrexone Prevents in Males and Attenuates in Females the Expression of Behavioral Sensitization to Ethanol Regardless of Maternal Separation

    Science.gov (United States)

    Kawakami, Suzi E.; Quadros, Isabel M. H.; Suchecki, Deborah

    2016-01-01

    Maternal separation alters the activity of the opioid system, which modulates ethanol-induced stimulation and behavioral sensitization. This study examined the effects of an opioid antagonist, naltrexone (NTX), on the expression of behavioral sensitization to ethanol in adult male and female mice submitted to maternal separation from postnatal days (PNDs) 2 to 14. Whole litters of Swiss mice were either not separated [animal facility rearing (AFR)] or separated from their mothers for 3 h [long maternal separation (LMS)]. Starting on PND 90, male and female AFR and LMS mice received daily i.p. injections of saline (SAL) or ethanol (EtOH, 2.2 g/kg) for 21 days. Locomotor activity was assessed in cages containing photoelectric beams, once a week, to examine the development of behavioral sensitization. Five days after the end of the chronic treatment, animals were submitted to four locomotor activity tests spaced by 48 h, to assess the expression of behavioral sensitization. In all tests, animals received two i.p. injections with a 30-min interval and were then assessed for locomotor response to different treatment challenges, which were: SAL/SAL, SAL/EtOH (2.2 g/kg), NTX 2.0 mg/kg (NTX2)/EtOH, and NTX 4.0 mg/kg (NTX4)/EtOH. Regardless of maternal separation, EtOH-treated male and female mice displayed increased locomotor responses to EtOH during the 21-day treatment, indicating the development of behavioral sensitization. In the SAL/EtOH challenge, EtOH-treated LMS and AFR male and female mice exhibited higher locomotor activity than their SAL-treated counterparts, indicating the expression of sensitization. The coadministration of either dose of NTX blocked the expression of locomotor sensitization in both AFR and LMS male mice with a history of EtOH sensitization. In females, a significant attenuation of EtOH sensitization was promoted by both NTX doses, while still maintaining an augmented stimulant response to EtOH. Importantly, maternal separation

  1. Pattern of intake and drug craving predict the development of cocaine addiction-like behavior in rats.

    Science.gov (United States)

    Belin, David; Balado, Eric; Piazza, Pier Vincenzo; Deroche-Gamonet, Véronique

    2009-05-15

    Clinical observations suggest that cocaine addiction often emerges with new patterns of use. Whether these changes are a cause of addiction or its consequence is unknown. We investigated whether the development of an addiction-like behavior in the rat is associated with the pattern of cocaine intake and with cocaine craving, a major feature of cocaine addiction. To determine whether changes in the pattern of cocaine use and enhanced craving precede or parallel the onset of addiction, we used a rat addiction model that incorporates core features of human addiction. For this purpose, the pattern of inter-infusion intervals (a measure of pattern of cocaine intake), sensitivity to cocaine-induced reinstatement (a measure of cocaine craving), and addiction-like behaviour were assessed over several months of intravenous cocaine self-administration. We found that, even at early stages of cocaine self-administration, both the pattern of cocaine intake and the intensity of drug-induced reinstatement predict the severity of cocaine use, measured after 75 days of self-administration. Our results identify key predictors of cocaine addiction-intensified pattern of drug use and high drug-induced craving-that may help in the identification of subjects at risk for subsequent development of severe cocaine addiction.

  2. Developmentally sensitive cognitive behavioral therapy for adolescent school refusal: rationale and case illustration.

    Science.gov (United States)

    Heyne, David; Sauter, Floor M; Ollendick, Thomas H; Van Widenfelt, Brigit M; Westenberg, P Michiel

    2014-06-01

    School refusal can be difficult to treat and the poorest treatment response is observed among older school refusers. This poor response may be explained, in part, by the impact of developmental transitions and tasks upon the young person, their family, and the treatment process. This paper describes and illustrates the @school program, a cognitive behavioral therapy (CBT) designed to promote developmental sensitivity when planning and delivering treatment for adolescent school refusal. Treatment is modularized and it incorporates progress reviews, fostering a planned yet flexible approach to CBT. The treatment is illustrated in the case of Allison, a 16-year-old female presenting with major depressive disorder and generalized anxiety disorder. A case formulation guided the selection, sequencing, and pacing of modules targeting predisposing, precipitating, perpetuating, and protective factors. Treatment comprised 16 sessions with Allison (interventions addressing depression, anxiety, and school attendance) and 15 concurrent sessions with her mother (strategies to facilitate an adolescent's school attendance), including two sessions with Allison and mother together (family communication and problem solving to reduce parent-adolescent conflict). Two treatment-related consultations were also conducted with Allison's homeroom teacher. Allison's school attendance improved during the course of treatment. By post-treatment, there was a decrease in internalizing behavior, an increase in self-efficacy, and remission of depressive disorder and anxiety disorder. Clinically significant treatment gains were maintained at 2-month follow-up. Factors influencing outcome may include those inherent to the @school program together with less specific factors. Special consideration is given to parents' use of both authoritative and autonomy-granting approaches when helping an adolescent to attend school.

  3. Brief predator sound exposure elicits behavioral and neuronal long-term sensitization in the olfactory system of an insect

    DEFF Research Database (Denmark)

    Anton, S.; Evengaard, K.; Barrozo, R. B.

    2011-01-01

    these processes have been described. However, the influence of sensory signals on the sensitivity of a different modality is largely unknown. In males of the noctuid moth, Spodoptera littoralis, the sensitivity to the female-produced sex pheromone increases 24 h after a brief preexposure with pheromone...... at the behavioral and central nervous level. Here we show that this effect is not confined to the same sensory modality: the sensitivity of olfactory neurons can also be modulated by exposure to a different sensory stimulus, i.e., a pulsed stimulus mimicking echolocating sounds from attacking insectivorous bats. We......, but also on the central nervous level, in an insect....

  4. Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice : spinal cord c-Fos expression and behavior

    NARCIS (Netherlands)

    Eijkelkamp, Niels; Kavelaars, Annemieke; Elsenbruch, Sigrid; Schedlowski, Manfred; Holtmann, Gerald; Heijnen, Cobi J.

    2007-01-01

    Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior. Am J Physiol Gastrointest Liver Physiol 293: G749-G757, 2007. First published July 26, 2007; doi:10.1152/ajpgi.00114.2007.During acute and chronic inflammation visceral pain perc

  5. Direct and indirect predictors of social anxiety: The role of anxiety sensitivity, behavioral inhibition, experiential avoidance and self-consciousness.

    Science.gov (United States)

    Panayiotou, Georgia; Karekla, Maria; Panayiotou, Margarita

    2014-11-01

    Using mediated and moderated regression, this study examined the hypothesis that anxiety sensitivity, the tendency to be concerned about anxiety symptoms, and behavioral inhibition, the tendency to withdraw from novel and potentially dangerous stimuli, predict social anxiety indirectly through experiential avoidance as measured by the Acceptance and Action Questionnaire-II and self-consciousness, as measured by the Self-Consciousness Scale. Behavioral inhibition and anxiety sensitivity are operationalized as temperamental traits, while experiential avoidance and self-consciousness are seen as learned emotion regulation strategies. Study 1 included college student groups from Cyprus scoring high and low on social anxiety (N=64 and N=63) as measured by the Social Phobia and Anxiety Inventory. Study 2 examined a random community sample aged 18-65 (N=324) treating variables as continuous and using the Psychiatric Disorders Screening Questionnaire to screen for social anxiety. Results suggest that experiential avoidance, but not self-consciousness mediates the effects of anxiety sensitivity on predicting social anxiety status, but that behavioral inhibition predicts social anxiety directly and not through the proposed mediators. Moderation effects were not supported. Overall, the study finds that social anxiety symptomatology is predicted not only by behavioral inhibition, but also anxiety sensitivity, when individuals take actions to avoid anxious experiences. Modifying such avoidant coping approaches may be more beneficial for psychological treatments than attempts to change long-standing, temperamental personality traits.

  6. Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice : spinal cord c-Fos expression and behavior

    NARCIS (Netherlands)

    Eijkelkamp, Niels; Kavelaars, Annemieke; Elsenbruch, Sigrid; Schedlowski, Manfred; Holtmann, Gerald; Heijnen, Cobi J.

    2007-01-01

    Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior. Am J Physiol Gastrointest Liver Physiol 293: G749-G757, 2007. First published July 26, 2007; doi:10.1152/ajpgi.00114.2007.During acute and chronic inflammation visceral pain

  7. Activation of D2 autoreceptors alters cocaine-induced locomotion and slows down local field oscillations in the rat ventral tegmental area.

    Science.gov (United States)

    Koulchitsky, Stanislav; Delairesse, Charlotte; Beeken, Thom; Monteforte, Alexandre; Dethier, Julie; Quertemont, Etienne; Findeisen, Rolf; Bullinger, Eric; Seutin, Vincent

    2016-09-01

    Psychoactive substances affecting the dopaminergic system induce locomotor activation and, in high doses, stereotypies. Network mechanisms underlying the shift from an active goal-directed behavior to a "seemingly purposeless" stereotypic locomotion remain unclear. In the present study we sought to determine the relationships between the behavioral effects of dopaminergic drugs and their effects on local field potentials (LFPs), which were telemetrically recorded within the ventral tegmental area (VTA) of freely moving rats. We used the D2/D3 agonist quinpirole in a low, autoreceptor-selective (0.1 mg/kg, i.p.) and in a high (0.5 mg/kg, i.p.) dose, and a moderate dose of cocaine (10 mg/kg, i.p.). In the control group, power spectrum analysis revealed a prominent peak of LFP power in the theta frequency range during active exploration. Cocaine alone stimulated locomotion, but had no significant effect on the peak of the LFP power. In contrast, co-administration of low dose quinpirole with cocaine markedly altered the pattern of locomotion, from goal-directed exploratory behavior to recurrent motion resembling locomotor stereotypy. This behavioral effect was accompanied by a shift of the dominant theta power toward a significantly lower (by ∼15%) frequency. High dose quinpirole also provoked an increased locomotor activity with signs of behavioral stereotypies, and also induced a shift of the dominant oscillation frequency toward the lower range. These results demonstrate a correlation between the LFP oscillation frequency within the VTA and a qualitative aspect of locomotor behavior, perhaps due to a variable level of coherence of this region with its input or output areas.

  8. Luteolin inhibits behavioral sensitization by blocking methamphetamine-induced MAPK pathway activation in the caudate putamen in mice.

    Directory of Open Access Journals (Sweden)

    Tinglin Yan

    Full Text Available GOAL: To investigate the effect of luteolin on methamphetamine (MA-induced behavioral sensitization and mitogen-activated protein kinase (MAPK signal transduction pathway activation in mice. METHODS: Mice received a single dose of MA to induce hyperactivity or repeated intermittent intraperitoneal injections of MA to establish an MA-induced behavioral sensitization mouse model. The effect of luteolin on the development and expression of MA-induced hyperactivity and behavioral sensitization was examined. The expression and activity of ΔFosB and the levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2, phosphorylated c-Jun N-terminal kinase (pJNK, and phosphorylated p38 mitogen-activated protein kinase (pp38 in the caudate putamen (CPu were measured by western blot. RESULTS: Luteolin significantly decreased hyperactivity as well as the development and expression of MA-induced behavioral sensitization in mice. ΔFosB, pERK1/2, and pJNK levels in the CPu were higher in MA-treated mice than in control mice, whereas the pp38 level did not change. Injection of luteolin inhibited the MA-induced increase in ΔFosB, pERK1/2, and pJNK levels, but did not affect the pp38 level. CONCLUSIONS: Luteolin inhibits MA-induced hyperactivity and behavioral sensitization in mice through the ERK1/2/ΔFosB pathway. Furthermore, the JNK signaling pathway might be involved in MA-induced neurodegeneration in the CPu, and luteolin inhibits this process.

  9. Acute total sleep deprivation potentiates amphetamine-induced locomotor-stimulant effects and behavioral sensitization in mice.

    Science.gov (United States)

    Saito, Luis P; Fukushiro, Daniela F; Hollais, André W; Mári-Kawamoto, Elisa; Costa, Jacqueline M; Berro, Laís F; Aramini, Tatiana C F; Wuo-Silva, Raphael; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

    2014-02-01

    It has been demonstrated that a prolonged period (48 h) of paradoxical sleep deprivation (PSD) potentiates amphetamine (AMP)-induced behavioral sensitization, an animal model of addiction-related neuroadaptations. In the present study, we examined the effects of an acute short-term deprivation of total sleep (TSD) (6h) on AMP-induced behavioral sensitization in mice and compared them to the effects of short-term PSD (6 h). Three-month-old male C57BL/6J mice underwent TSD (experiment 1-gentle handling method) or PSD (experiment 2-multiple platforms method) for 6 h. Immediately after the sleep deprivation period, mice were tested in the open field for 10 min under the effects of saline or 2.0 mg/kg AMP. Seven days later, to assess behavioral sensitization, all of the mice received a challenge injection of 2.0 mg/kg AMP and were tested in the open field for 10 min. Total, peripheral, and central locomotion, and grooming duration were measured. TSD, but not PSD, potentiated the hyperlocomotion induced by an acute injection of AMP and this effect was due to an increased locomotion in the central squares of the apparatus. Similarly, TSD facilitated the development of AMP-induced sensitization, but only in the central locomotion parameter. The data indicate that an acute period of TSD may exacerbate the behavioral effects of AMP in mice. Because sleep architecture is composed of paradoxical and slow wave sleep, and 6-h PSD had no effects on AMP-induced hyperlocomotion or sensitization, our data suggest that the deprivation of slow wave sleep plays a critical role in the mechanisms that underlie the potentiating effects of TSD on both the acute and sensitized addiction-related responses to AMP.

  10. A comparison of auditory brainstem responses and behavioral estimates of hearing sensitivity in Lemur catta and Nycticebus coucang.

    Science.gov (United States)

    Ramsier, Marissa A; Dominy, Nathaniel J

    2010-03-01

    Primates depend on acoustic signals and cues to avoid predators, locate food, and share information. Accordingly, the structure and function of acoustic stimuli have long been emphasized in studies of primate behavioral and cognitive ecology. Yet, few studies have addressed how well primates hear such stimuli; indeed, the auditory thresholds of most primate species are unknown. This empirical void is due in part to the logistic and economic challenges attendant on traditional behavioral testing methods. Technological advances have produced a safe and cost-effective alternative-the auditory brainstem response (ABR) method, which can be utilized in field conditions, on virtually any animal species, and without subject training. Here we used the ABR and four methods of threshold determination to construct audiograms for two strepsirrhine primates: the ring-tailed lemur (Lemur catta) and slow loris (Nycticebus coucang). Next, to verify the general efficacy of the ABR method, we compared our results to published behaviorally-derived audiograms. We found that the four ABR threshold detection methods produced similar results, including relatively elevated thresholds but similarly shaped audiograms compared to those derived behaviorally. The ABR and behavioral absolute thresholds were significantly correlated, and the frequencies of best sensitivity and high-frequency limits were comparable. However, at frequencies Lemur, the ABR 10-dB range starting points were more than 2 octaves higher than the behavioral points. Finally, a comparison of ABR- and behaviorally-derived audiograms from various animal taxa demonstrates the widespread efficacy of the ABR for estimating frequency of best sensitivity, but otherwise suggests caution; factors such as stimulus properties and threshold definition affect results. We conclude that the ABR method is a promising technique for estimating primate hearing sensitivity, but that additional data are required to explore its efficacy for

  11. Stereochemistry and neuropharmacology of a ‘bath salt’ cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates

    Science.gov (United States)

    Vouga, Alexandre; Gregg, Ryan A.; Haidery, Maryah; Ramnath, Anita; Al-Hassani, Hassan K.; Tallarida, Christopher S.; Grizzanti, David; Raffa, Robert B.; Smith, Garry R.; Reitz, Allen B.; Rawls, Scott M.

    2015-01-01

    Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100–1000 μM) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 μM) and racemate (100 μM) produced EPC, but S-MEPH was ineffective at all concentrations (10–100 μM). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 μM) produced EPC that was abolished when S-MEPH (100 μM) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 μM) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10–250 μM). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own. PMID:25496724

  12. Stereochemistry and neuropharmacology of a 'bath salt' cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates.

    Science.gov (United States)

    Vouga, Alexandre; Gregg, Ryan A; Haidery, Maryah; Ramnath, Anita; Al-Hassani, Hassan K; Tallarida, Christopher S; Grizzanti, David; Raffa, Robert B; Smith, Garry R; Reitz, Allen B; Rawls, Scott M

    2015-04-01

    Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100-1000 μM) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 μM) and racemate (100 μM) produced EPC, but S-MEPH was ineffective at all concentrations (10-100 μM). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 μM) produced EPC that was abolished when S-MEPH (100 μM) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 μM) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10-250 μM). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own.

  13. The effects of Valeriana officinalis L. hydro-alcoholic extract on depression like behavior in ovalbumin sensitized rats

    Directory of Open Access Journals (Sweden)

    Ali Neamati

    2014-01-01

    Full Text Available Background: Neuroimmune factors have been considered as contributors to the pathogenesis of depression. Beside other therapeutic effects, Valeriana officinalis L., have been suggested to have anti-inflammatory effects. In the present study, the effects of V. officinalis L. hydro alcoholic extract was investigated on depression like behavior in ovalbumin sensitized rats. Materials and Methods: A total of 50 Wistar rats were divided into five groups: Group 1 (control group received saline instead of Valeriana officinalis L. extract. The animals in group 2 (sensitized were treated by saline instead of the extract and were sensitized using the ovalbumin. Groups 3-5 (Sent - Ext 50, (Sent - Ext 100 and (Sent - Ext 200 were treated by 50, 100 and 200 mg/kg of V. officinalis L. hydro-alcoholic extract respectively, during the sensitization protocol. Forced swimming test was performed for all groups and immobility time was recorded. Finally, the animals were placed in the open-field apparatus and the crossing number on peripheral and central areas was observed. Results: The immobility time in the sensitized group was higher than that in the control group (P < 0.01. The animals in Sent-Ext 100 and Sent-Ext 200 groups had lower immobility times in comparison with sensitized group (P < 0.05 and P < 0.01. In the open field test, the crossed number in peripheral by the sensitized group was higher than that of the control one (P < 0.01 while, the animals of Sent-Ext 50, Sent-Ext 100 and Sent-Ext 200 groups had lower crossing number in peripheral compared with the sensitized group (P < 0.05 and P < 0.01 respectively. Furthermore, in the sensitized group, the central crossing number was lower than that of the control group (P < 0.001. In the animals treated by 200 mg/kg of the extract, the central crossing number was higher than that of the sensitized group (P < 0. 05. Conclusions: The results of the present study showed that the hydro-alcoholic extract of V

  14. Testing the role of reward and punishment sensitivity in avoidance behavior: a computational modeling approach

    OpenAIRE

    Sheynin, Jony; Moustafa, Ahmed A.; Beck, Kevin D.; Servatius, Richard J.; Myers, Catherine E.

    2015-01-01

    Exaggerated avoidance behavior is a predominant symptom in all anxiety disorders and its degree often parallels the development and persistence of these conditions. Both human and non-human animal studies suggest that individual differences as well as various contextual cues may impact avoidance behavior. Specifically, we have recently shown that female sex and inhibited temperament, two anxiety vulnerability factors, are associated with greater duration and rate of the avoidance behavior, as...

  15. Enhancement of behavioral sensitization, anxiety-like behavior, and hippocampal and frontal cortical CREB levels following cocaine abstinence in mice exposed to cocaine during adolescence.

    Directory of Open Access Journals (Sweden)

    Maria Cristina Valzachi

    Full Text Available Adolescence has been linked to greater risk-taking and novelty-seeking behavior and a higher prevalence of drug abuse and risk of relapse. Decreases in cyclic adenosine monophosphate response element binding protein (CREB and phosphorylated CREB (pCREB have been reported after repeated cocaine administration in animal models. We compared the behavioral effects of cocaine and abstinence in adolescent and adult mice and investigated possible age-related differences in CREB and pCREB levels. Adolescent and adult male Swiss mice received one daily injection of saline or cocaine (10 mg/kg, i.p. for 8 days. On day 9, the mice received a saline injection to evaluate possible environmental conditioning. After 9 days of withdrawal, the mice were tested in the elevated plus maze to evaluate anxiety-like behavior. Twelve days after the last saline/cocaine injection, the mice received a challenge injection of either cocaine or saline, and locomotor activity was assessed. One hour after the last injection, the brains were extracted, and CREB and pCREB levels were evaluated using Western blot in the prefrontal cortex (PFC and hippocampus. The cocaine-pretreated mice during adolescence exhibited a greater magnitude of the expression of behavioral sensitization and greater cocaine withdrawal-induced anxiety-like behavior compared with the control group. Significant increases in CREB levels in the PFC and hippocampus and pCREB in the hippocampus were observed in cocaine-abstinent animals compared with the animals treated with cocaine in adulthood. Interestingly, significant negative correlations were observed between cocaine sensitization and CREB levels in both regions. These results suggest that the behavioral and neurochemical consequences of psychoactive substances in a still-developing nervous system can be more severe than in an already mature nervous system.

  16. Simulation of the strain rate sensitive flow behavior of SiC-particulate reinforced aluminum metal matrix composites

    OpenAIRE

    Tirtom, İsmail; Güden, Mustafa; Yıldız, Hasan

    2008-01-01

    Strain rate dependent compression mechanical behavior of an SiC-particulate reinforced Al (2024-O) metal matrix composite (MMC) with different particle volume fractions was numerically investigated at various strain rates. Calculations were performed using axisymmetric finite element unit cell model, in which an elastic SiC particle was embedded inside a strain rate sensitive viscoplastic Al matrix. Stress–strain curves of Al matrix material were derived from Split Hopkinson Pressure Bar expe...

  17. Not all risk taking behavior is bad: Associative sensitivity predicts learning during risk taking among high sensation seekers.

    Science.gov (United States)

    Humphreys, Kathryn L; Lee, Steve S; Tottenham, Nim

    2013-04-01

    Risk taking behavior can be both adaptive and maladaptive depending on context. The majority of studies of risk taking, however, focus on clinical populations and dangerous or harmful risk taking. Individual differences in learning during risk taking are rarely examined in relation to task performance. The present study examined risk taking and associated outcomes in an exploration-based instrumental learning task (Balloon Emotional Learning Task; BELT), which presented a series of balloons in which participants pump up for points. Consistent with prior work, sensation seeking predicted increased risk taking behavior. Importantly, however, a significant interaction between sensation seeking and associative sensitivity, an attentional construct defined as the frequency and remoteness of automatic cognitive activity, was found. Specifically, among individuals high in sensation seeking, associative sensitivity predicted fewer balloon explosions and an increase in points earned on the balloon condition with the most potential feedback driven learning. Thus, these findings suggest that sensation seekers are a heterogeneous group, and secondary traits such as associative sensitivity moderate behavior such as risk taking and learning according to context.

  18. The behavioral effects of chronic sugar and/or caffeine consumption in adult and adolescent rats.

    Science.gov (United States)

    Franklin, Jane L; Wearne, Travis A; Homewood, Judi; Cornish, Jennifer L

    2017-08-01

    Caffeine is a psychostimulant frequently consumed by adults and children, often in combination with high levels of sugar. Chronic pretreatment with either substance can amplify both amphetamine and cocaine-induced hyperactivity in rodents. The present study sought to elucidate whether age at the time of exposure to sugar and/or caffeine alters sensitivity to an acute illicit psychostimulant (methamphetamine, [METH]) challenge in adulthood. Adult and adolescent (Postnatal Day 35 on first day of treatment) male Sprague-Dawley rats were treated for 26 days with water, caffeine (0.6 g/L), 10% sucrose or their combination. Locomotor behavior was measured on the first and last day of treatment. Following 9-days treatment free, animals were challenged with saline (1 ml/kg, i.p.) or METH (1 mg/kg, i.p.) and locomotor activity was measured. During the treatment period, adolescent rats maintained a higher caffeine (mg/kg) dose than their adult counterparts. Adding sugar to caffeine increased adolescent consumption and the highest caffeine dose consumed was measured in these animals. Drinking sugar-sweetened caffeinated water or combination did not produce cross-sensitization to METH administration in either age group. Nevertheless, the finding that regular exposure through adolescence to caffeinated sugar-sweetened beverages could increase consumption of caffeine and sugar later in life is important, as there is a large body of evidence that has linked excess consumption of sugar-sweetened beverages to a broad range of other negative physical and mental health outcomes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. The sensitivity of lateral line receptors and their role in the behavior of Mexican blind cavefish (Astyanax mexicanus)

    Science.gov (United States)

    Yoshizawa, Masato; Jeffery, William R.; van Netten, Sietse M.; McHenry, Matthew J.

    2014-01-01

    The characid fish species Astyanax mexicanus offers a classic comparative model for the evolution of sensory systems. Populations of this species evolved in caves and became blind while others remained in streams (i.e. surface fish) and retained a functional visual system. The flow-sensitive lateral line receptors, called superficial neuromasts, are more numerous in cavefish than in surface fish, but it is unclear whether individual neuromasts differ in sensitivity between these populations. The aims of this study were to determine whether the neuromasts in cavefish impart enhanced sensitivity relative to surface fish and to test whether this aids their ability to sense flow in the absence of visual input. Sensitivity was assessed by modeling the mechanics and hydrodynamics of a flow stimulus. This model required that we measure the dimensions of the transparent cupula of a neuromast, which was visualized with fluorescent microspheres. We found that neuromasts within the eye orbit and in the suborbital region were larger and consequently about twice as sensitive in small adult cavefish as in surface fish. Behavioral experiments found that these cavefish, but not surface fish, were attracted to a 35 Hz flow stimulus. These results support the hypothesis that the large superficial neuromasts of small cavefish aid in flow sensing. We conclude that the morphology of the lateral line could have evolved in cavefish to permit foraging in a cave environment. PMID:24265419

  20. The sensitivity of lateral line receptors and their role in the behavior of Mexican blind cavefish (Astyanax mexicanus).

    Science.gov (United States)

    Yoshizawa, Masato; Jeffery, William R; van Netten, Sietse M; McHenry, Matthew J

    2014-03-15

    The characid fish species Astyanax mexicanus offers a classic comparative model for the evolution of sensory systems. Populations of this species evolved in caves and became blind while others remained in streams (i.e. surface fish) and retained a functional visual system. The flow-sensitive lateral line receptors, called superficial neuromasts, are more numerous in cavefish than in surface fish, but it is unclear whether individual neuromasts differ in sensitivity between these populations. The aims of this study were to determine whether the neuromasts in cavefish impart enhanced sensitivity relative to surface fish and to test whether this aids their ability to sense flow in the absence of visual input. Sensitivity was assessed by modeling the mechanics and hydrodynamics of a flow stimulus. This model required that we measure the dimensions of the transparent cupula of a neuromast, which was visualized with fluorescent microspheres. We found that neuromasts within the eye orbit and in the suborbital region were larger and consequently about twice as sensitive in small adult cavefish as in surface fish. Behavioral experiments found that these cavefish, but not surface fish, were attracted to a 35 Hz flow stimulus. These results support the hypothesis that the large superficial neuromasts of small cavefish aid in flow sensing. We conclude that the morphology of the lateral line could have evolved in cavefish to permit foraging in a cave environment.

  1. Supertaster, super reactive: oral sensitivity for bitter taste modulates emotional approach and avoidance behavior in the affective startle paradigm.

    Science.gov (United States)

    Herbert, Cornelia; Platte, Petra; Wiemer, Julian; Macht, Michael; Blumenthal, Terry D

    2014-08-01

    People differ in both their sensitivity for bitter taste and their tendency to respond to emotional stimuli with approach or avoidance. The present study investigated the relationship between these sensitivities in an affective picture paradigm with startle responding. Emotion-induced changes in arousal and attention (pupil modulation), priming of approach and avoidance behavior (startle reflex modulation), and subjective evaluations (ratings) were examined. Sensitivity for bitter taste was assessed with the 6-n-propylthiouracil (PROP)-sensitivity test, which discriminated individuals who were highly sensitive to PROP compared to NaCl (PROP-tasters) and those who were less sensitive or insensitive to the bitter taste of PROP. Neither pupil responses nor picture ratings differed between the two taster groups. The startle eye blink response, however, significantly differentiated PROP-tasters from PROP-insensitive subjects. Facilitated response priming to emotional stimuli emerged in PROP-tasters but not in PROP-insensitive subjects at shorter startle lead intervals (200-300ms between picture onset and startle stimulus onset). At longer lead intervals (3-4.5s between picture onset and startle stimulus onset) affective startle modulation did not differ between the two taster groups. This implies that in PROP-sensitive individuals action tendencies of approach or avoidance are primed immediately after emotional stimulus exposure. These results suggest a link between PROP taste perception and biologically relevant patterns of emotional responding. Direct perception-action links have been proposed to underlie motivational priming effects of the startle reflex, and the present results extend these to the sensory dimension of taste.

  2. Weather and place-based human behavior: recreational preferences and sensitivity

    Science.gov (United States)

    de Freitas, C. R.

    2015-01-01

    This study examines the links between biometeorological variables and the behavior of beach recreationists along with their rating of overall weather conditions. To identify and describe significance of on-site atmospheric conditions, two separate forms of response are examined. The first is sensory perception of the immediate atmospheric surround expressed verbally, which was the subject of earlier work. In the research reported here, on-site observations of behavior that reflect the effects of weather and climate are examined. By employing, independently, separate indicators of on-site experience, the reliability of each is examined and interpreted and apparent threshold conditions verified. The study site is King's Beach located on the coast of Queensland, Australia. On-site observations of atmospheric variables and beach user behavior are made for the daylight hours of 45 days spread over a 12-month period. The results show that behavioral data provide reliable and meaningful indications of the significance of the atmospheric environment for leisure. Atmospheric conditions within the zone of acceptability are those that the beach users can readily cope with or modify by a range of minor behavioral adjustments. Optimal weather conditions appear to be those requiring no specific behavioral adjustment. Attendance levels reflect only the outer limits of acceptability of the meteorological environment, while duration of visit enables calibration of levels of approval in so far as it reflects rating of on-site weather within a broad zone of tolerance. In a broad theoretical sense, the results add to an understanding of the relationship between weather and human behavior. This information is potentially useful in effective tourism management and planning.

  3. Weather and place-based human behavior: recreational preferences and sensitivity.

    Science.gov (United States)

    de Freitas, C R

    2015-01-01

    This study examines the links between biometeorological variables and the behavior of beach recreationists along with their rating of overall weather conditions. To identify and describe significance of on-site atmospheric conditions, two separate forms of response are examined. The first is sensory perception of the immediate atmospheric surround expressed verbally, which was the subject of earlier work. In the research reported here, on-site observations of behavior that reflect the effects of weather and climate are examined. By employing, independently, separate indicators of on-site experience, the reliability of each is examined and interpreted and apparent threshold conditions verified. The study site is King's Beach located on the coast of Queensland, Australia. On-site observations of atmospheric variables and beach user behavior are made for the daylight hours of 45 days spread over a 12-month period. The results show that behavioral data provide reliable and meaningful indications of the significance of the atmospheric environment for leisure. Atmospheric conditions within the zone of acceptability are those that the beach users can readily cope with or modify by a range of minor behavioral adjustments. Optimal weather conditions appear to be those requiring no specific behavioral adjustment. Attendance levels reflect only the outer limits of acceptability of the meteorological environment, while duration of visit enables calibration of levels of approval in so far as it reflects rating of on-site weather within a broad zone of tolerance. In a broad theoretical sense, the results add to an understanding of the relationship between weather and human behavior. This information is potentially useful in effective tourism management and planning.

  4. Measures of Behavioral Inhibition and Activation System Sensitivity as Predictors of Big Five Personality Traits

    Directory of Open Access Journals (Sweden)

    Valerija Križanić

    2015-07-01

    Full Text Available In the Reinforcement Sensitivity Theory, Gray (1987 described three hypothetical biological brain systems, assumed to represent underpinnings of the stable patterns of experience and behaviour. Most research has been devoted to studying behavioural inhibition system (BIS and behavioural activation system (BAS, which have shown relatively stable associations with neuroticism and extroversion, respectively. BIS/BAS scale (Carver & White, 1994 is one of the most frequently used instruments for measuring these constructs. The questionnaire contains one scale of BIS sensitivity that captures reactions to appearance or anticipation of punishment, and three subscales of BAS sensitivity which are aimed to assess distinct but related constructs: BAS – Drive, that relate to persistence in achieving desired goals; BAS - Fun seeking, that relates to desire for new rewarding experiences and indicates person's readiness to engage in potentially rewarding situation, and BAS – Reward sensitivity, that measures positive reactions to appearance or anticipation of reward.The aim of the current study was to explore to what extent individual differences in personality traits can be predicted based on measures of BIS and BAS sensitivity. In this paper we analysed the data of 284 female students, that completed translated and adapted Croatian version of BIS/BAS scales, as well as International Personality Item Pool (IPIP 50 which measures the Big-Five personality domains. Exploratory factor analysis indicated that the factor structure of Croatian version of BIS/BAS scale was comparable to the original instrument. Results of the regression analysis revealed that BIS scale was a significant predictor of emotional instability, while BAS subscales showed different patterns of relationships with measured personality traits. These results indicate the importance of measuring distinct aspects of BAS sensitivity.

  5. The C. elegans D2-like dopamine receptor DOP-3 decreases behavioral sensitivity to the olfactory stimulus 1-octanol.

    Directory of Open Access Journals (Sweden)

    Meredith J Ezak

    Full Text Available We previously found that dopamine signaling modulates the sensitivity of wild-type C. elegans to the aversive odorant 1-octanol. C. elegans lacking the CAT-2 tyrosine hydroxylase enzyme, which is required for dopamine biosynthesis, are hypersensitive in their behavioral avoidance of dilute concentrations of octanol. Dopamine can also modulate the context-dependent response of C. elegans lacking RGS-3 function, a negative regulator of G alpha signaling. rgs-3 mutant animals are defective in their avoidance of 100% octanol when they are assayed in the absence of food (E. coli bacterial lawn, but their response is restored when they are assayed in the presence of food or exogenous dopamine. However, it is not known which receptor might be mediating dopamine's effects on octanol avoidance. Herein we describe a role for the C. elegans D2-like receptor DOP-3 in the regulation of olfactory sensitivity. We show that DOP-3 is required for the ability of food and exogenous dopamine to rescue the octanol avoidance defect of rgs-3 mutant animals. In addition, otherwise wild-type animals lacking DOP-3 function are hypersensitive to dilute octanol, reminiscent of cat-2 mutants. Furthermore, we demonstrate that DOP-3 function in the ASH sensory neurons is sufficient to rescue the hypersensitivity of dop-3 mutant animals, while dop-3 RNAi knockdown in ASH results in octanol hypersensitivity. Taken together, our data suggest that dopaminergic signaling through DOP-3 normally acts to dampen ASH signaling and behavioral sensitivity to octanol.

  6. Pavlovian conditioning and cross-sensitization studies raise challenges to the hypothesis that overeating is an addictive behavior.

    Science.gov (United States)

    Harb, M R; Almeida, O F X

    2014-04-29

    Elevated glucocorticoid levels and sign tracking (ST) in Pavlovian conditioning are potential biomarkers of compulsive behaviors such as addiction. As overeating is sometimes viewed as a form of addictive behavior, we hypothesized that murine Pavlovian sign trackers would have a greater propensity to overeat and develop obesity. Using a food reward in the classical conditioning paradigm, we show that ST behavior is a robust conditioned response but not a predictor of eating and growth trajectories in mice, thus challenging the view that the development of obesity and drug addiction depend on identical mechanisms. This interpretation was supported by experiments which showed that overweight mice do not display cross-sensitization to an addictive drug (morphine), and conversely, that overweight morphine-sensitized animals do not overconsume a highly rewarding food. Although the rewarding/motivational effects of both food and drugs of abuse are mediated by similar neurochemical mechanisms, obesity and drug addiction represent a summation of other dysfunctional input and output pathways that lead to the emergence of two distinct disorders, each of which would deserve a specific pharmacotherapeutic approach.

  7. Aggressive Behavior between Siblings and the Development of Externalizing Problems: Evidence from a Genetically Sensitive Study

    Science.gov (United States)

    Natsuaki, Misaki N.; Ge, Xiaojia; Reiss, David; Neiderhiser, Jenae M.

    2009-01-01

    This study investigated the prospective links between sibling aggression and the development of externalizing problems using a multilevel modeling approach with a genetically sensitive design. The sample consisted of 780 adolescents (390 sibling pairs) who participated in 2 waves of the Nonshared Environment in Adolescent Development project.…

  8. Genetic Sensitivity to Peer Behaviors: "5HTTLPR", Smoking, and Alcohol Consumption

    Science.gov (United States)

    Daw, Jonathan; Shanahan, Michael; Harris, Kathleen Mullan; Smolen, Andrew; Haberstick, Brett; Boardman, Jason D.

    2013-01-01

    We investigate whether the serotonin transporter-linked polymorphic region ("5HTTLPR"), a gene associated with environmental sensitivity, moderates the association between smoking and drinking patterns at adolescents' schools and their corresponding risk for smoking and drinking themselves. Drawing on the school-based design of the National…

  9. Genetic Sensitivity to Peer Behaviors: "5HTTLPR", Smoking, and Alcohol Consumption

    Science.gov (United States)

    Daw, Jonathan; Shanahan, Michael; Harris, Kathleen Mullan; Smolen, Andrew; Haberstick, Brett; Boardman, Jason D.

    2013-01-01

    We investigate whether the serotonin transporter-linked polymorphic region ("5HTTLPR"), a gene associated with environmental sensitivity, moderates the association between smoking and drinking patterns at adolescents' schools and their corresponding risk for smoking and drinking themselves. Drawing on the school-based design of the National…

  10. Sensitization and Habituation of Motivated Behavior in Overweight and Non-Overweight Children

    Science.gov (United States)

    Epstein, Leonard H.; Robinson, Jodie L.; Temple, Jennifer L.; Roemmich, James N.; Marusewski, Angela; Nadbrzuch, Rachel

    2008-01-01

    The rate of habituation to food is inversely related to energy intake, and overweight children may habituate slower to food and consume more energy. This study compared patterns of sensitization, as defined by an initial increase in operant or motivated responding for food, and habituation, defined by gradual reduction in responding, for macaroni…

  11. Examination of smoking inflexibility as a mechanism linking anxiety sensitivity and severity of smoking behavior.

    Science.gov (United States)

    Jardin, Charles; Bakhshaie, Jafar; Schmidt, Norman B; Sharp, Carla; Zvolensky, Michael

    2015-06-01

    Anxiety sensitivity is associated with smoking processes and poorer clinical outcomes. Yet, the specific mechanisms underlying this association are unclear. Smoking-specific avoidance and inflexibility (AIS) is a construct implicated in multiple manifestations of mood regulation that may underlie smoking severity. The current study examined whether AIS accounted for (ie, statistically mediated) the relationship between anxiety sensitivity and multiple indices of smoking severity. Baseline self-report data were collected among treatment-seeking smokers (N = 396; 48% female; Mage  = 37.8 years) taking part in a larger intervention study. Gender, smoking-related medical history, Axis I diagnoses, hazardous alcohol use, substance abuse/dependence, and negative affectivity were statistically controlled in analyses. Anxiety sensitivity was indirectly related to all smoking severity variables, with the exception of nicotine dependence, through its relation with AIS. These findings provide initial evidence suggesting AIS may be an important construct in better understanding anxiety sensitivity-smoking relations. Results suggest the importance of AIS as a malleable target for smoking cessation intervention. © American Academy of Addiction Psychiatry.

  12. Sensitization and Habituation of Motivated Behavior in Overweight and Non-Overweight Children

    Science.gov (United States)

    Epstein, Leonard H.; Robinson, Jodie L.; Temple, Jennifer L.; Roemmich, James N.; Marusewski, Angela; Nadbrzuch, Rachel

    2008-01-01

    The rate of habituation to food is inversely related to energy intake, and overweight children may habituate slower to food and consume more energy. This study compared patterns of sensitization, as defined by an initial increase in operant or motivated responding for food, and habituation, defined by gradual reduction in responding, for macaroni…

  13. Responsive Social Agents: Feedback-Sensitive Behavior Generation for Social Interactions

    NARCIS (Netherlands)

    Vroon, Jered Hendrik; Agah, Arvin; Englebienne, Gwenn; Cabibihan, John-John; Howard, Ayanna M.; Evers, Vanessa; Salichs, Miguel A.; He, Hongsheng

    How can we generate appropriate behavior for social artificial agents? A common approach is to (1) establish with controlled experiments which action is most appropriate in which setting, and (2) select actions based on this knowledge and an estimate of the setting. This approach faces challenges,

  14. Behavior and sensitivity of an optimal tree diameter growth model under data uncertainty

    Science.gov (United States)

    Don C. Bragg

    2005-01-01

    Using loblolly pine, shortleaf pine, white oak, and northern red oak as examples, this paper considers the behavior of potential relative increment (PRI) models of optimal tree diameter growth under data uncertainity. Recommendations on intial sample size and the PRI iteractive curve fitting process are provided. Combining different state inventories prior to PRI model...

  15. Navigating Monogamy: Nonapeptide Sensitivity in a Memory Neural Circuit May Shape Social Behavior and Mating Decisions.

    Science.gov (United States)

    Ophir, Alexander G

    2017-01-01

    The role of memory in mating systems is often neglected despite the fact that most mating systems are defined in part by how animals use space. Monogamy, for example, is usually characterized by affiliative (e.g., pairbonding) and defensive (e.g., mate guarding) behaviors, but a high degree of spatial overlap in home range use is the easiest defining feature of monogamous animals in the wild. The nonapeptides vasopressin and oxytocin have been the focus of much attention for their importance in modulating social behavior, however this work has largely overshadowed their roles in learning and memory. To date, the understanding of memory systems and mechanisms governing social behavior have progressed relatively independently. Bridging these two areas will provide a deeper appreciation for understanding behavior, and in particular the mechanisms that mediate reproductive decision-making. Here, I argue that the ability to mate effectively as monogamous individuals is linked to the ability to track conspecifics in space. I discuss the connectivity across some well-known social and spatial memory nuclei, and propose that the nonapeptide receptors within these structures form a putative "socio-spatial memory neural circuit." This purported circuit may function to integrate social and spatial information to shape mating decisions in a context-dependent fashion. The lateral septum and/or the nucleus accumbens, and neuromodulation therein, may act as an intermediary to relate socio-spatial information with social behavior. Identifying mechanisms responsible for relating information about the social world with mechanisms mediating mating tactics is crucial to fully appreciate the suite of factors driving reproductive decisions and social decision-making.

  16. Effect of pH on the flocculation behaviors of kaolin using a pH-sensitive copolymer.

    Science.gov (United States)

    Li, Shulei; Gao, Lihui; Cao, Yijun; Gui, Xiahui; Li, Zhen

    pH-sensitive copolymers have been widely introduced to achieve rapid dewatering and consolidation of solids in mining and oil sands processing wastes. But no more attention has been given to the flocculation efficiency of solid suspensions as a function of pH using pH-sensitive copolymer. In this study, a pH-sensitive copolymer was synthesized and employed to investigate the flocculation behaviors of kaolin by focused beam reflectance measurement (FBRM). A titration test was introduced to characterize the copolymer conformation transition. The results demonstrated that at pH ranging from 3 to 6, with the pH increase, the zeta potential magnitude of kaolin particles increased, resulting in the repulsive forces between particles increasing. However, the hydrophobicity of kaolin increased as the pH increased. Thus, the hydrophobic forces could neutralize a part of the repulsive forces between particles and result in good and similar flocculation performances. At the pH greater than 6, the zeta potential magnitude of kaolin particles and copolymer molecules increased significantly, and the repulsive force between kaolin particles increased after copolymer addition due to the kaolin particles being more negatively charged, which resulted in poor flocculation efficiency and cloudy supernatant. It was concluded that the pH-sensitive copolymer could achieve both perfect flocculation efficiency and low moisture of filter cake at the isoelectric point of copolymer.

  17. Neuropeptide s alters anxiety but not depression-like behaviors in the flinders sensitive line rats, a genetic animal model

    DEFF Research Database (Denmark)

    Mathe, A.; Wegener, Gregers; Finger, B.

    2010-01-01

    of cannula, 0.25 or 1.0 nmol NPS, or vehicle/5 ml were infused into the lateral ventricle. 45 min after NPS infusion animals were tested on elevated plus maze (EPM). Five days later the animals were subjected to the two-day forced swim test (FST); NPS or vehicle were injected 45 min before the second day FST...... the effects of centrally administered NPS on depression- and anxiety-related behaviors, using a well validated animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL). Methods: Male and female were tested. Seven days following insertion...... while no difference in the anxiety-like behavior was observed. These findings confirm the utility of the FSL as a model of depression useful in exploration of neurobiological correlates both of depression and those discriminating between depression and anxiety endophenotypes. NPS had marked anxiolytic...

  18. Midbrain Synchrony to Envelope Structure Supports Behavioral Sensitivity to Single-Formant Vowel-Like Sounds in Noise.

    Science.gov (United States)

    Henry, Kenneth S; Abrams, Kristina S; Forst, Johanna; Mender, Matthew J; Neilans, Erikson G; Idrobo, Fabio; Carney, Laurel H

    2017-02-01

    Vowels make a strong contribution to speech perception under natural conditions. Vowels are encoded in the auditory nerve primarily through neural synchrony to temporal fine structure and to envelope fluctuations rather than through average discharge rate. Neural synchrony is thought to contribute less to vowel coding in central auditory nuclei, consistent with more limited synchronization to fine structure and the emergence of average-rate coding of envelope fluctuations. However, this hypothesis is largely unexplored, especially in background noise. The present study examined coding mechanisms at the level of the midbrain that support behavioral sensitivity to simple vowel-like sounds using neurophysiological recordings and matched behavioral experiments in the budgerigar. Stimuli were harmonic tone complexes with energy concentrated at one spectral peak, or formant frequency, presented in quiet and in noise. Behavioral thresholds for formant-frequency discrimination decreased with increasing amplitude of stimulus envelope fluctuations, increased in noise, and were similar between budgerigars and humans. Multiunit recordings in awake birds showed that the midbrain encodes vowel-like sounds both through response synchrony to envelope structure and through average rate. Whereas neural discrimination thresholds based on either coding scheme were sufficient to support behavioral thresholds in quiet, only synchrony-based neural thresholds could account for behavioral thresholds in background noise. These results reveal an incomplete transformation to average-rate coding of vowel-like sounds in the midbrain. Model simulations suggest that this transformation emerges due to modulation tuning, which is shared between birds and mammals. Furthermore, the results underscore the behavioral relevance of envelope synchrony in the midbrain for detection of small differences in vowel formant frequency under real-world listening conditions.

  19. Fractalkine receptor (CX3CR1 deficiency sensitizes mice to the behavioral changes induced by lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Kelley Keith W

    2010-12-01

    Full Text Available Abstract Background Interactions between fractalkine (CX3CL1 and fractalkine receptor (CX3CR1 regulate microglial activation in the CNS. Recent findings indicate that age-associated impairments in CX3CL1 and CX3CR1 are directly associated with exaggerated microglial activation and an impaired recovery from sickness behavior after peripheral injection of lipopolysaccharide (LPS. Therefore, the purpose of this study was to determine the extent to which an acute LPS injection causes amplified and prolonged microglial activation and behavioral deficits in CX3CR1-deficient mice (CX3CR1-/-. Methods CX3CR1-/- mice or control heterozygote mice (CX3CR1+/- were injected with LPS (0.5 mg/kg i.p. or saline and behavior (i.e., sickness and depression-like behavior, microglial activation, and markers of tryptophan metabolism were determined. All data were analyzed using Statistical Analysis Systems General Linear Model procedures and were subjected to one-, two-, or three-way ANOVA to determine significant main effects and interactions. Results LPS injection caused a prolonged duration of social withdrawal in CX3CR1-/- mice compared to control mice. This extended social withdrawal was associated with enhanced mRNA expression of IL-1β, indolamine 2,3-dioxygenase (IDO and kynurenine monooxygenase (KMO in microglia 4 h after LPS. Moreover, elevated expression of IL-1β and CD14 was still detected in microglia of CX3CR1-/- mice 24 h after LPS. There was also increased turnover of tryptophan, serotonin, and dopamine in the brain 24 h after LPS, but these increases were independent of CX3CR1 expression. When submitted to the tail suspension test 48 and 72 h after LPS, an increased duration of immobility was evident only in CX3CR1-/- mice. This depression-like behavior in CX3CR1-/- mice was associated with a persistent activated microglial phenotype in the hippocampus and prefrontal cortex. Conclusions Taken together, these data indicate that a deficiency of CX3CR1

  20. Efficient behavior of photosynthetic organelles via Pareto optimality, identifiability, and sensitivity analysis.

    Science.gov (United States)

    Carapezza, Giovanni; Umeton, Renato; Costanza, Jole; Angione, Claudio; Stracquadanio, Giovanni; Papini, Alessio; Lió, Pietro; Nicosia, Giuseppe

    2013-05-17

    In this work, we develop methodologies for analyzing and cross comparing metabolic models. We investigate three important metabolic networks to discuss the complexity of biological organization of organisms, modeling, and system properties. In particular, we analyze these metabolic networks because of their biotechnological and basic science importance: the photosynthetic carbon metabolism in a general leaf, the Rhodobacter spheroides bacterium, and the Chlamydomonas reinhardtii alga. We adopt single- and multi-objective optimization algorithms to maximize the CO 2 uptake rate and the production of metabolites of industrial interest or for ecological purposes. We focus both on the level of genes (e.g., finding genetic manipulations to increase the production of one or more metabolites) and on finding concentration enzymes for improving the CO 2 consumption. We find that R. spheroides is able to absorb an amount of CO 2 until 57.452 mmol h (-1) gDW (-1) , while C. reinhardtii obtains a maximum of 6.7331. We report that the Pareto front analysis proves extremely useful to compare different organisms, as well as providing the possibility to investigate them with the same framework. By using the sensitivity and robustness analysis, our framework identifies the most sensitive and fragile components of the biological systems we take into account, allowing us to compare their models. We adopt the identifiability analysis to detect functional relations among enzymes; we observe that RuBisCO, GAPDH, and FBPase belong to the same functional group, as suggested also by the sensitivity analysis.

  1. Impulsive Action, Psychological Stress, and Behavioral Sensitization to Nicotine in a Rat Model of lmpulsivity

    Science.gov (United States)

    2010-06-30

    place preference in type 1 cannabinoid receptor knockout mice. Behavioural Pharmacology, 19, 575-581. 18m .1 •• \\ " 195 Mirjana, C., Baviera, M...administration by administering a CRF-1 receptor antagonist. Additionally, CRF affected motivated behavior in an ethanol self- administration paradigm, with...CRF-1 receptor antagonists dose-dependently decreasing ethanol self-administration during withdrawal in dependent rats (Valdez et aI., 2002). Because

  2. Effect of ethylene glycol dimethacrylate on swelling and on metformin hydrochloride release behavior of chemically crosslinked pH-sensitive acrylic acid-polyvinyl alcohol hydrogel

    National Research Council Canada - National Science Library

    Akhtar, Muhammad Faheem; Ranjha, Nazar Muhammad; Hanif, Muhammad

    2015-01-01

    The present work objective was to prepare and to observe the effect of ethylene glycol dimethacrylate on swelling and on drug release behavior of pH-sensitive acrylic acid-polyvinyl alcohol hydrogel...

  3. Cadmium Increases the Sensitivity of Adolescent Female Mice to Nicotine-Related Behavioral Deficits

    OpenAIRE

    Philip Adeyemi Adeniyi; Babawale Peter Olatunji; Azeez Olakunle Ishola; Duyilemi Chris Ajonijebu; Olalekan Michael Ogundele

    2014-01-01

    This study investigates spatial and nonspatial working memory, anxiety related behavior, and motor activities in cadmium and/or nicotine exposed female adolescent mice. P28 female adolescent mice (albino strain) were divided into four groups of five (n = 5) mice each. A set of mice (Nic) received subcutaneous nicotine (2.0 mg/kg) while a separate set (Cd) was treated with 2.0 mg/kg cadmium (subcutaneous). For the combined treatments of cadmium and nicotine, we administered 2.0 mg/kg Nicotine ...

  4. High-resolution linkage analyses to identify genes that influence Varroa sensitive hygiene behavior in honey bees.

    Science.gov (United States)

    Tsuruda, Jennifer M; Harris, Jeffrey W; Bourgeois, Lanie; Danka, Robert G; Hunt, Greg J

    2012-01-01

    Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera) and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Varroa sensitive hygiene behavior is one of two behaviors identified that are most important for controlling the growth of Varroa populations in bee hives. To identify genes influencing this trait, a study was conducted to map quantitative trait loci (QTL). Individual workers of a backcross family were observed and evaluated for their VSH behavior in a mite-infested observation hive. Bees that uncapped or removed pupae were identified. The genotypes for 1,340 informative single nucleotide polymorphisms were used to construct a high-resolution genetic map and interval mapping was used to analyze the association of the genotypes with the performance of Varroa sensitive hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21) and a suggestive QTL on chromosome 1 (LOD = 1.95). The QTL confidence interval on chromosome 9 contains the gene 'no receptor potential A' and a dopamine receptor. 'No receptor potential A' is involved in vision and olfaction in Drosophila, and dopamine signaling has been previously shown to be required for aversive olfactory learning in honey bees, which is probably necessary for identifying mites within brood cells. Further studies on these candidate genes may allow for breeding bees with this trait using marker-assisted selection.

  5. Development of a multiphysics model to characterize the responsive behavior of urea-sensitive hydrogel as biosensor.

    Science.gov (United States)

    Goh, K B; Li, Hua; Lam, K Y

    2017-05-15

    A remarkable feature of biomaterials is their ability to deform in response to certain external bio-stimuli. Here, a novel biochemo-electro-mechanical model is developed for the numerical characterization of the urea-sensitive hydrogel in response to the external stimulus of urea. The urea sensitivity of the hydrogel is usually characterized by the states of ionization and denaturation of the immobilized urease, as such the model includes the effect of the fixed charge groups and temperature coupled with pH on the activity of the urease. Therefore, a novel rate of reaction equation is proposed to characterize the hydrolysis of urea that accounts for both the ionization and denaturation states of the urease subject to the environmental conditions. After examination with the published experimental data, it is thus confirmed that the model can characterize well the responsive behavior of the urea-sensitive hydrogel subject to the urea stimulus, including the distribution patterns of the electrical potential and pH of the hydrogel. The results point to an innovative means for generating electrical power via the enzyme-induced pH and electrical potential gradients, when the hydrogel comes in contact with the urea-rich solution, such as human urine.

  6. Long-term behavioral sensitization to apomorphine is independent of conditioning and increases conditioned pecking, but not preference, in pigeons.

    Science.gov (United States)

    Anselme, Patrick; Edeş, Neslihan; Tabrik, Sepideh; Güntürkün, Onur

    2017-08-30

    When rodents are given a free choice between a variable option and a constant option, they may prefer variability. This preference is even sometimes increased following repeated administration of a dopamine agonist. The present study was the first to examine preference for variability under the systemic administration of a dopamine agonist, apomorphine (Apo), in birds. Experiment 1 tested the drug-free preference and the propensity to choose of pigeons for a constant over a variable delay. It appeared that they preferred and decided more quickly to peck at the optimal delay option. Experiment 2 assessed the effects of a repeated injection of Apo on delay preference, in comparison with previous control tests within the same individuals. Apo treatment might have decreased the number of pecks at the constant option across the different experimental phases, but failed to induce a preference for the variable option. In Experiment 3, two groups of pigeons (Apo-sensitized and saline) were used in order to avoid inhomogeneity in treatments. They had to choose between a 50% probability option and a 5-s delay option. Conditioned pecking and the propensity to choose were higher in the Apo-sensitized pigeons, but, in each group, the pigeons showed indifference between the two options. This experiment also showed that long-term behavioral sensitization to Apo can occur independently of a conditioning process. These results suggest that Apo sensitization can enhance the attractiveness of conditioned cues, while having no effect on the development of a preference for variable-delay and probabilistic schedules of reinforcement. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Lesões destrutivas da linha média induzidas por cocaína com ANCA positivo mimetizando a granulomatose de Wegener Cocaine-induced midline destruction lesions with positive ANCA test mimicking Wegener's granulomatosis

    Directory of Open Access Journals (Sweden)

    Letícia Stahelin

    2012-06-01

    diagnosed with WG for five months, being on prednisone and cyclophosphamide. On her physical examination, perforation of her nasal septum and palate was observed. Laboratory tests showed elevated acute phase proteins and a positive p-ANCA test. ELISA assays anti-proteinase 3 and myeloperoxidase were negative. The paranasal sinus computed tomography (CT showed destruction of the nasal septum and palate, in addition to bilateral maxillary sinusitis. Chest CT was normal. Nasal mucosal biopsy revealed an inflammatory infiltrate, with neither granuloma nor vasculitis. When questioned, she admitted being a cocaine user for five years. Medical therapy and cocaine use were withdrawn. She has been followed up for six months and no other lesion or other organ symptoms occurred. Differential diagnosis in patients with midline destructive lesions can be very challenging. Evaluation should include enquiry about intranasal use of cocaine. Although ANCA testing does not clearly differentiate the ANCA found in some patients with CIMDL from those found in WG patients, the localized involvement and the biopsy findings non-characteristic of small vessel granulomatous vasculitis should be recognized as features for cocaine-induced lesions.

  8. 本米对可卡因所致小鼠急性肝损伤的保护作用%Protective effects of benmi against cocaine-induced hepatotoxicity in mice

    Institute of Scientific and Technical Information of China (English)

    王璐; 丁兆丰; 敬挺; 贾凤兰; 阮明; 何月莹; 吕艳; 张宝旭

    2011-01-01

    . Significant amelioration in liver histopathology was also presented in the Benmi treatment group. Conclusions This experiment suggested that Benmi has significant protective effect against cocaine-induced hepatotoxicity in mice.

  9. Inhibition of interleukin-6 function attenuates the central sensitization and pain behavior induced by osteoarthritis.

    Science.gov (United States)

    Lin, Yuangui; Liu, Lian; Jiang, Haixia; Zhou, Jieshu; Tang, Yuying

    2017-09-15

    Chronic pain is the most prominent and disabling symptom in the patients with osteoarthritis (OA), and the underlying mechanism largely remains unclear. Interleukin-6 (IL-6), a proinflammatory cytokine, is critically involved in the development and maintenance of central sensitization in several rodent models of chronic pain. The present study aims to elucidate the IL-6 mediated neurological adaptation in dorsal horn in the rat with monosodium iodoacetate (MIA) - induced OA. Significant upregulation of IL-6 expression was detected in the dorsal horn in the modeled rats. Blockade of IL-6 function by tocilizumab markedly suppressed the activation of astrocytes and microglia in the ipsilateral dorsal horn, reduced c-Fos immunoreactivity in dorsal horn neurons, and attenuated the upregulation of glutamate receptor subunits GluR1 and NR2B in dorsal horn in the rats with MIA-induced OA. It was further reported that administration of tocilizumab significantly improved the performance in weight-bearing test and mitigated the mechanical allodynia in the modeled rats. These data illustrated spinal IL-6 mediated mechanism underlying the chronic pain, and proposed the potential therapeutic effect of tocilizumab on the chronic pain in the setting of OA. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. ASSOCIATION BEHAVIOR OF PORPHYRIN PENDANTS IN pH-SENSITIVE WATER-SOLUBLE POLYMER

    Institute of Scientific and Technical Information of China (English)

    Ke-wei Ding; Fei Wang; Fei-peng Wu

    2012-01-01

    A novel tripyridylporphyrin monomer,5-[4-[2-(acryloyloxy)ethoxy]phenyl]-10,15,20-tris(4-pyridyl)porphyrin (TrPyP),was synthesized and polymerized with acrylamide (AM) to prepare the hydrophobically associating water-soluble polymer PAM-TrPyP.The aggregation behavior of porphyrin pendants was investigated by UV-Visible and fluorescence spectra.The polymer displays a strong tendency of hydrophobic association even in dilute solutions.With increasing the concentration,the maximum absorption wavelength of Sorer band changes from 416 nm to 407 nm,and the fluorescence corrected for the inner filter effect exhibits moderate concentration quenching.All the results indicate that π-π interaction of porphyrin pendants plays a key role in association of PAM-TrPyP,and H-aggregates of porphyrins are mainly formed in the conccntrated solution.On the other hand,dynamic light scattering (DLS) and transmission electron microscopy (TEM) were used to follow the changes in size and structure of the macromolecular assemblies with the concentration increase.The polymer aggregation conformation changes from loose "vesicle-like" morphology to solid globule accordingly.When pH value of solution decreases to 4.3,pyridine moieties on porphyrin pendants could be protonated and the H-aggregates formed in macromolecular matrix are destroyed by electrostatic repulsion interactions.

  11. Cadmium Increases the Sensitivity of Adolescent Female Mice to Nicotine-Related Behavioral Deficits

    Directory of Open Access Journals (Sweden)

    Philip Adeyemi Adeniyi

    2014-01-01

    Full Text Available This study investigates spatial and nonspatial working memory, anxiety related behavior, and motor activities in cadmium and/or nicotine exposed female adolescent mice. P28 female adolescent mice (albino strain were divided into four groups of five (n=5 mice each. A set of mice (Nic received subcutaneous nicotine (2.0 mg/kg while a separate set (Cd was treated with 2.0 mg/kg cadmium (subcutaneous. For the combined treatments of cadmium and nicotine, we administered 2.0 mg/kg Nicotine and 2.0 mg/kg of Cd. Subsequently, a separate group of animals (n=5; control received normal saline. The total duration of treatment for all groups was 28 days (P28–P56. At P56, the treatment was discontinued, after which the animals were examined in behavioural tests. Nicotine and cadmium increased the metabolism and food intake in the female adolescent mice. This also corresponded to an increase in weight when compared with the control. However, a combined nicotine-cadmium treatment induced a decline in weight of the animals versus the control. Also, nicotine administration increased the motor function, while cadmium and nicotine-cadmium treatment caused a decline in motor activity. Both nicotine and cadmium induced a reduction in memory index; however, nicotine-cadmium treatment induced the most significant decrease in nonspatial working memory.

  12. Sensitivity of injected argon behavior to changes in magnetic balance in double-null plasmas in DIII-D

    Energy Technology Data Exchange (ETDEWEB)

    Petrie, T.W. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States)], E-mail: petrie@fusion.gat.com; Brooks, N.H. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Fenstermacher, M.E.; Groth, M. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94551 (United States); Hyatt, A.W. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Lasnier, C.J. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94551 (United States); Leonard, A.W. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Porter, G.D. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, CA 94551 (United States); Schaffer, M.J.; Wade, M.R. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Watkins, J.G. [Sandia National Laboratories, P.O. Box 5800, Albuquerque, NM 87185 (United States); West, W.P. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States)

    2009-06-15

    Recent DIII-D experiments show that both magnetic balance and particle drifts are important to understanding how argon impurities accumulate in balanced and unbalanced double-null plasmas during 'puff and pump' radiating divertor operation. Unbalanced double-null shapes, which are biased in the direction opposite to the ion Bx{nabla}B drift direction, have produced the best result to-date in terms of coupling a radiating divertor approach with an H-mode plasma. The proximity to balanced double-null that can be used for puff-and-pump may depend on the width of the heat flux profile in the scrape-off layer. A comparison of plasma behavior in the open lower divertor to that of the more closed upper divertor determined that plasma density control was far more sensitive to the ion Bx{nabla}B drift direction than to the relative closure of the divertor.

  13. Loss of zebrafish lgi1b leads to hydrocephalus and sensitization to pentylenetetrazol induced seizure-like behavior.

    Directory of Open Access Journals (Sweden)

    Yong Teng

    Full Text Available Mutations in the LGI1 gene predispose to a hereditary epilepsy syndrome and is the first gene associated with this disease which does not encode an ion channel protein. In zebrafish, there are two paralogs of the LGI1 gene, lgi1a and lgi1b. Knockdown of lgi1a results in a seizure-like hyperactivity phenotype with associated developmental abnormalities characterized by cellular loss in the eyes and brain. We have now generated knockdown morphants for the lgi1b gene which also show developmental abnormalities but do not show a seizure-like behavior. Instead, the most striking phenotype involves significant enlargement of the ventricles (hydrocephalus. As shown for the lgi1a morphants, however, lgi1b morphants are also sensitized to PTZ-induced hyperactivity. The different phenotypes between the two lgi1 morphants support a subfunctionalization model for the two paralogs.

  14. Biomechanics of chiasmal compression: Sensitivity of the mechanical behaviors of nerve fibers to variations in material property and geometry

    Science.gov (United States)

    Wang, Xiaofei; Neely, Andrew J.; McIlwaine, Gawn G.; Lueck, Christian J.

    2016-05-01

    The mechanism of bitemporal hemianopia is still unclear. Previous research suggested that the nerve fiber packing pattern may contribute to the selective damage of nasal (crossed) nerve fibers. Numerical models were built using finite element modeling to study the biomechanics of optic nerve fibers. The sensitivity of the mechanical behaviors of the nerve fibers to variations of five parameters in the nerve fiber model were investigated using design of experiments (DOE). Results show that the crossing angle is a very significant factor that affects a wide range of responses of the model. The strain difference between the crossed and the uncrossed nerve fibers may account for the phenomenon of bitemporal hemianopia. This work also highlights the need for more accurate material properties of the tissues in the model and an improved understanding of the microstructure of the optic chiasm.

  15. The Temporal Course of Anxiety Sensitivity in Outpatients with Anxiety and Mood Disorders: Relationships with Behavioral Inhibition and Depression

    Science.gov (United States)

    Rosellini, Anthony J.; Fairholme, Christopher P.; Brown, Timothy A.

    2011-01-01

    The present study evaluated the temporal course of three dimensions of anxiety sensitivity (AS; concerns over physical symptoms, mental incapacitation, and social embarrassment) and their relationships with behavioral inhibition (BI) and depression (DEP) in 606 outpatients with anxiety and mood disorders. A semi-structured interview and self-report questionnaires were administered on three occasions over a two-year period. All three constructs decreased over the study period and AS temporally functioned more similar to DEP than BI. Cross-sectional and temporal correlations supported the discriminant validity of AS from BI. As expected, initial levels of BI predicted less improvement in all AS dimensions. In contrast, higher initial levels of mental incapacitation AS were associated with greater improvement in DEP. Our results are discussed in regard to the measurement of AS in clinical samples, conceptualizations of AS as a lower-order vulnerability, and prognostic implications of directional paths between BI and AS and AS and DEP. PMID:21377316

  16. Application of Ultrasonic Attenuation Measurements in the Studies on Macromolecular Conformational Behaviors--Phase Behavior of the Aqueous Solution of Poly(vinyl methyl ether) Sensitive to Temperature and the Modification of the Behavior by Using Poly(ac

    Institute of Scientific and Technical Information of China (English)

    WANG,Gong-Zheng(王公正); FANG,Yu(房喻); SHANG,Zhi-Yuan(尚志远); ZHANG,Ying(张颖); HU,Dao-Dao(胡道道)

    2004-01-01

    The phase behavior of the aqueous solution of poly(vinyl methyl ether) (PVME) sensitive to temperature and the modification of the behavior by using poly(acrylic acid) (PAA) have been studied by ultrasonic attenuation measurements and fluorescence probe techniques. It has been observed that PVME solution is transparent at room temperature and becomes turbid upon heating. The solution turns clear again as soon as the temperature is decreased to room temperature. The heating and cooling process can be repeated for many times. The phase behavior of the solution sensitive to temperature is attributed to the conformational changes of the polymer. PVME may adopt an open coil conformation at room temperature. With this conformation, the polymer is well miscible with the solvent, water, and thereby the system is a real solution. The polymer may adopt a compact coil conformation when the temperature is higher than a specific value, which is called the LCST (the lower critical solution temperature) of PVME. In this case, the polymer tangles to each other and forms various aggregates, which can scatter incident light and ultrasonic waves greatly, resulting in the phase separation. Introduction of PAA decreases the temperature sensitivity of the phase behavior of the polymer. The nature of the inhibition is attributed to the complexation of PAA with PVME and the strong hydrophilicity of PAA. Results from fluorescence probe studies are in accordance with those from ultrasonic attenuation measurements, indicating again that the ultrasonic attenuation method can be successfully used for the qualitative studies of polymer conformations and complexation between polymers.

  17. Sensitivity analysis of torsional vibration behavior of the shafting of a turbo generator set to changes of its mechanical parameters

    Institute of Scientific and Technical Information of China (English)

    XIE Danmei; LIU Zhanhui; ZHANG Hengliang; YANG Changzhu; DONG Chuan

    2007-01-01

    Aiming at a 300 MW turbo-generator model,the sensitivity of natural torsional frequencies and modes of torsional vibration (TV) to the rotational inertia and stiffness of the turbo-generator were analyzed.Calculation results show that the variation of the rotational inertia or stiffness either of the rotor system as a whole (namely shafting) or only locally may both remarkably influence the TV characteristics of the rotor.The influence of localized variation is still notable although it is not as great as that of the rotor as a whole.The segments on the shafting,which contribute more to a certain mode of vibration,have a greater influence on the pertaining order of TV.Compared with the modal shape,a larger slope can be observed at these sections of the rotor for the particular mode.Thus,frequencies can be modulated by modifying the local construction of the rotor to make the natural TV frequency of a certain order avoid some specific value,herewith arriving at the objective of tuning.Therefore,it is very important,in the course of modeling for the purpose of studying the TV of the shafting of a turbo-set,to accurately determine the structural parameters of parts that have a relatively sensitive effect on the TV behavior.

  18. Sensitivity of Cosmic-Ray Proton Spectra to the Low-wavenumber Behavior of the 2D Turbulence Power Spectrum

    Science.gov (United States)

    Engelbrecht, N. E.; Burger, R. A.

    2015-12-01

    In this study, a novel ab initio cosmic ray (CR) modulation code that solves a set of stochastic transport equations equivalent to the Parker transport equation, and that uses output from a turbulence transport code as input for the diffusion tensor, is introduced. This code is benchmarked with a previous approach to ab initio modulation. The sensitivity of computed galactic CR proton spectra at Earth to assumptions made as to the low-wavenumber behavior of the two-dimensional (2D) turbulence power spectrum is investigated using perpendicular mean free path expressions derived from two different scattering theories. Constraints on the low-wavenumber behavior of the 2D power spectrum are inferred from the qualitative comparison of computed CR spectra with spacecraft observations at Earth. Another key difference from previous studies is that observed and inferred CR intensity spectra at 73 AU are used as boundary spectra instead of the usual local interstellar spectrum. Furthermore, the results presented here provide a tentative explanation as to the reason behind the unusually high galactic proton intensity spectra observed in 2009 during the recent unusual solar minimum.

  19. Dopamine Receptor Gene DRD4 7-Repeat Allele X Maternal Sensitivity Interaction on Child Externalizing Behavior Problems: Independent Replication of Effects at 18 Months.

    Science.gov (United States)

    King, Anthony P; Muzik, Maria; Hamilton, Lindsay; Taylor, Alexander B; Rosenblum, Katherine L; Liberzon, Israel

    2016-01-01

    The DRD4 VNTR has been associated with child behavior problems in interaction with maternal insensitivity in European and American cohorts of preschoolers, with the 7-repeat (7R) allele associated with greater problems. We sought to replicate and expand these findings by examining effects on reports of child behavior problems at 18 months. A 63 family sample with data for observed maternal sensitivity ratings, DRD4 VNTR genotype, and maternal report of child behavior problems at 18-months was used in this preliminary analysis. Maternal sensitivity was measured at 6-months of age using laboratory observational measures (free-play and a teaching task). Maternal report of toddler behavior was obtained at 18-months via the standard Child Behavior Checklist, and infant genotype on the DRD4 VNTR was obtained using PCR. Infants carrying the DRD4 7R allele showed greater effects of maternal insensitivity than non-carriers for behavioral problems at 18-months. We replicated previous findings of association of infant DRD4 x maternal sensitivity interactions with child Externalizing problems in the European-ancestry sample (N = 42) in a median split of maternal sensitivity (p = .00011, eta2 = .329) and in regression analyses controlling for maternal age, maternal depression, and child gender in European ancestry (B = -3.4, SE 1.33, p = .01) and the total sample (B = -2.2, SE 1.02, p = .02). Exploratory analyses also found evidence of DRD4 x maternal sensitivity interaction with the CBCL ADHD scale. These findings replicate in an independent cohort DRD4 x maternal insensitivity interaction effect on child externalizing behavior problems at 18 months, further supporting the role of the DRD4 genotype in differential sensitivity to parenting.

  20. Ifenprodil Attenuates Methamphetamine-Induced Behavioral Sensitization and Activation of Ras-ERK-∆FosB Pathway in the Caudate Putamen.

    Science.gov (United States)

    Li, Lu; Liu, Xinshe; Qiao, Chuchu; Chen, Gang; Li, Tao

    2016-10-01

    Addiction is a debilitating, chronic psychiatric disorder that is difficult to cure completely owing to the high rate of relapse. Behavioral sensitization is considered to may underlie behavioral changes, such as relapse, caused by chronic abuse of psychomotor stimulants. Thus, its animal models have been widely used to explore the etiology of addiction. Recently, increasing evidence has demonstrated that N-methyl-D-aspartate receptors (NMDARs) play an important role in addiction to psychomotor stimulants. However, the role of GluN2B-containing receptors and their downstream signaling pathway(s) in behavioral sensitization induced by methamphetamine (METH) have not been investigated yet. In this study, we used different doses of ifenprodil (2.5, 5, 10 mg/kg), a selective antagonist of the GluN2B subunit, to investigate the role of GluN2B-containing NMDARs in METH-induced behavioral sensitization. We then examined changes in the levels of Ras, phosphorylated extracellular signal-regulated kinase (pERK)/ERK, and ∆FosB in the caudate putamen (CPu) by western blot. We found that 2.5 or 10 mg/kg ifenprodil significantly attenuated METH-induced behavioral sensitization, whereas the mice treated with a moderate dose of ifenprodil (5 mg/kg) displayed no significant changes. Further results of western blot experiments showed that repeated administration of METH caused the increases in the levels of Ras, pERK/ERK and ∆FosB in the CPu, and these changes were inhibited by only the 2.5 mg/kg dose of ifenprodil. In conclusion, these results demonstrated that 2.5 mg/kg ifenprodil could attenuate METH-induced behavioral sensitization. Moreover, GluN2B-containing NMDARs and their downstream Ras-ERK-∆FosB signaling pathway in the CPu might be involved in METH-induced behavioral sensitization.

  1. Neural Correlates of Inflexible Behavior in the Orbitofrontal–Amygdalar Circuit after Cocaine Exposure

    Science.gov (United States)

    STALNAKER, THOMAS A.; ROESCH, MATTHEW R.; CALU, DONNA J.; BURKE, KATHRYN A.; SINGH, TEGHPAL; SCHOENBAUM, GEOFFREY

    2008-01-01

    Addiction is characterized by compulsive or inflexible behavior, observed both in the context of drug-seeking and in contexts unrelated to drugs. One possible contributor to these inflexible behaviors may be drug-induced dysfunction within circuits that support behavioral flexibility, including the basolateral amygdala (ABL) and the orbitofrontal cortex (OFC). Here we describe data demonstrating that chronic cocaine exposure causes long-lasting changes in encoding properties in the ABL and the OFC during learning and reversal in an odor-guided task. In particular, these data suggest that inflexible encoding in ABL neurons may be the proximal cause of cocaine-induced behavioral inflexibility, and that a loss of outcome-expectant encoding in OFC neurons could be a more distal contributor to this impairment. A similar mechanism of drug-induced orbitofrontal–amygdalar dysfunction may cause inflexible behavior when animals and addicts are exposed to drug-associated cues and contexts. PMID:17846156

  2. Post-transcriptional regulation of dopamine D1 receptor expression in caudate-putamen of cocaine-sensitized mice.

    Science.gov (United States)

    Tobón, Krishna E; Catuzzi, Jennifer E; Cote, Samantha R; Sonaike, Adenike; Kuzhikandathil, Eldo V

    2015-07-01

    The dopamine D1 receptor is centrally involved in mediating the effects of cocaine and is essential for cocaine-induced locomotor sensitization. Changes in D1 receptor expression have been reported in various models of cocaine addiction; however, the mechanisms that mediate these changes in D1 receptor expression are not well understood. Using preadolescent drd1a-EGFP mice and a binge cocaine treatment protocol we demonstrate that the D1 receptor is post-transcriptionally regulated in the caudate-putamen of cocaine-sensitized animal. While cocaine-sensitized mice express high levels of steady-state D1 receptor mRNA, the expression of D1 receptor protein is not elevated. We determined that the post-transcriptional regulation of D1 receptor mRNA is rapidly attenuated and D1 receptor protein levels increase within 30 min when the sensitized mice are challenged with cocaine. The rapid increase in D1 receptor protein levels requires de novo protein synthesis and correlates with the cocaine-induced hyperlocomotor activity in the cocaine-sensitized mice. The increase in D1 receptor protein levels in the caudate-putamen inversely correlated with the levels of microRNA 142-3p and 382, both of which regulate D1 receptor protein expression. The levels of these two microRNAs decreased significantly within 5 min of cocaine challenge in sensitized mice. The results provide novel insights into the previously unknown rapid kinetics of D1 receptor protein expression which occurs in a time scale that is comparable to the expression of immediate early genes. Furthermore, the results suggest a potential novel role for inherently labile microRNAs in regulating the rapid expression of D1 receptor protein in cocaine-sensitized animals.

  3. Repeated exposure of male mice to low doses of lipopolysaccharide: dose and time dependent development of behavioral sensitization and tolerance in an automated light-dark anxiety test.

    Science.gov (United States)

    Banasikowski, Tomek J; Cloutier, Caylen J; Ossenkopp, Klaus-Peter; Kavaliers, Martin

    2015-06-01

    Although lipopolysaccharide (LPS) is widely used to examine immune behavior relationships there has been little consideration of the effects of low doses and the roles of sensitization and, or tolerance. Here low doses of LPS (1.0, 5.0 and 25.0 μg/kg) were peripherally administered to male mice on Days 1, 4, 28 and 32 after a baseline recording of anxiety-like behaviors in an automated light-dark apparatus (total time in the light chamber, number of light-dark transitions, nose pokes into the light chamber). LPS at 1.0 μg/kg, while having no significant effects on anxiety-like behaviors in the light-dark test on Days 1 and 4, displayed sensitization with the mice exhibiting significantly enhanced anxiety-like responses on Days 28 and 32. LPS at 5.0 μg/kg had no consistent significant effects on anxiety-like behavior on Days 1 and 4, with sensitization and enhanced anxiety-like behaviors on Day 28 followed by tolerance on Day 32. LPS at 25 μg/kg significantly enhanced anxiety-like behaviors on Day 1, followed by tolerance on Day 4, which was not evident by Day 28 and re-emerged on Day 32. There was a similar overall pattern of sensitization and tolerance for LPS-induced decreases in locomotor activity in the safe dark chamber, without, however, any significant effects on activity in the riskier light chamber. This shows that low doses of LPS induce anxiety-like behavior and these effects are subject to sensitization and tolerance in a dose, context, and time related manner.

  4. Action-potential duration and the modulation of transmitter release from the sensory neurons of Aplysia in presynaptic facilitation and behavioral sensitization

    OpenAIRE

    Hochner, Binyamin; Klein, Marc; Schacher, Samuel; Kandel, Eric R.

    1986-01-01

    Presynaptic facilitation of transmitter release from Aplysia sensory neurons is an important contributor to behavioral sensitization of the gill and siphon withdrawal reflex. The enhanced release is accompanied by reduction of the serotonin-sensitive S current in the sensory neurons and a consequent increase in duration of the presynaptic action potential (ranging from 10% to 30%). We find that changes of similar magnitude in the duration of depolarizing voltage-clamp steps in sensory neurons...

  5. MODAFINIL INDUCES RAPID-ONSET BEHAVIORAL SENSITIZATION AND CROSS-SENSTIZATION WITH COCAINE IN MICE: IMPLICATIONS FOR THE ADDICTIVE POTENTIAL OF MODAFINIL

    OpenAIRE

    Raphael Wuo-Silva; Daniela Fukushiro; André Hollais; Renan Baldaia; Elisa Kawamoto; Berro, Lais F. [UNIFESP; Thais Yokoyama; Leonardo Lopes-Silva; Carolina Bizerra; Roberta Procópio-Souza; Debora Hashiguchi; Lilian Figueiredo; Costa, José L; Roberto Frussa-Filho; Beatriz Monteiro Longo

    2016-01-01

    There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of dru...

  6. (*) Understanding the Spatiotemporal Degradation Behavior of Aggrecanase-Sensitive Poly(ethylene glycol) Hydrogels for Use in Cartilage Tissue Engineering.

    Science.gov (United States)

    Chu, Stanley; Sridhar, Shankar Lalitha; Akalp, Umut; Skaalure, Stacey C; Vernerey, Franck J; Bryant, Stephanie J

    2017-08-01

    Enzyme-sensitive hydrogels are promising cell delivery vehicles for cartilage tissue engineering. However, a better understanding of their spatiotemporal degradation behavior and its impact on tissue growth is needed. The goal of this study was to combine experimental and computational approaches to provide new insights into spatiotemporal changes in hydrogel crosslink density and extracellular matrix (ECM) growth and how these changes influence the evolving macroscopic properties as a function of time. Hydrogels were designed from aggrecanase-sensitive peptide crosslinks using a simple and robust thiol-norbornene photoclick reaction. To study the influence of variations in cellular activity of different donors, chondrocytes were isolated from either juvenile or adult bovine donors. Initial studies were performed to validate and calibrate the model against experiments. Through this process, two key features were identified. These included spatial variations in the hydrogel crosslink density in the immediate vicinity of the cell and the presence of cell clustering within the construct. When these spatial heterogeneities were incorporated into the computational model along with model inputs of initial hydrogel properties and cellular activity (i.e., enzyme and ECM production rates), the model was able to capture the spatial and temporal evolution of ECM growth that was observed experimentally for both donors. In this study, the juvenile chondrocytes produced an interconnected matrix within the cell clusters leading to overall improved ECM growth, while the adult chondrocytes resulted in poor ECM growth. Overall, the computational model was able to capture the spatiotemporal ECM growth of two different donors and provided new insights into the importance of spatial heterogeneities in facilitating ECM growth. Our long-term goal is to use this model to predict optimal hydrogel designs for a wide range of donors and improve cartilage tissue engineering.

  7. Sensitivity to reward and adolescents' unhealthy snacking and drinking behavior: the role of hedonic eating styles and availability.

    Science.gov (United States)

    De Cock, Nathalie; Van Lippevelde, Wendy; Goossens, Lien; De Clercq, Bart; Vangeel, Jolien; Lachat, Carl; Beullens, Kathleen; Huybregts, Lieven; Vervoort, Leentje; Eggermont, Steven; Maes, Lea; Braet, Caroline; Deforche, Benedicte; Kolsteren, Patrick; Van Camp, John

    2016-02-09

    Although previous research found a positive association between sensitivity to reward (SR) and adolescents' unhealthy snacking and drinking behavior, mechanisms explaining these associations remain to be explored. The present study will therefore examine whether the associations between SR and unhealthy snack and/or sugar-sweetened beverage (SSB) intake are mediated by external and/or emotional eating and if this mediation is moderated by availability at home or at school. Cross-sectional data on snacking, availability of snacks at home and at school, SR (BAS drive scale) and external and emotional eating (Dutch eating behavior questionnaire) of Flemish adolescents (n = 1104, mean age = 14.7 ± 0.8 years; 51 % boys; 18.0% overweight) in 20 schools spread across Flanders were collected. Moderated mediation analyses were conducted using generalized structural equation modeling in three steps: (1) direct association between SR and unhealthy snack or SSB intake, (2) mediation of either external or emotional eating and (3) interaction of home or school availability and emotional or external eating. Partial mediation of external eating (a*b = 0.69, p eating (a*b = 0.92, p unhealthy snacks was found (step 2). The relation between SR and SSB intake was not mediated by external or emotional eating (step 2). No moderation effects of home or school availability were found (step 3). Our findings indicate that the association between SR and the consumption of unhealthy snacks is partially explained by external and emotional eating in a population-based sample of adolescents irrespective of the home or school availability of these foods.

  8. Interparental conflict, parent psychopathology, hostile parenting, and child antisocial behavior: examining the role of maternal versus paternal influences using a novel genetically sensitive research design.

    Science.gov (United States)

    Harold, Gordon T; Elam, Kit K; Lewis, Gemma; Rice, Frances; Thapar, Anita

    2012-11-01

    Past research has linked interparental conflict, parent psychopathology, hostile parenting, and externalizing behavior problems in childhood. However, few studies have examined these relationships while simultaneously allowing the contribution of common genetic factors underlying associations between family- and parent-level variables on child psychopathology to be controlled. Using the attributes of a genetically sensitive in vitro fertilization research design, the present study examined associations among interparental conflict, parents' antisocial behavior problems, parents' anxiety symptoms, and hostile parenting on children's antisocial behavior problems among genetically related and genetically unrelated mother-child and father-child groupings. Path analyses revealed that for genetically related mothers, interparental conflict and maternal antisocial behavior indirectly influenced child antisocial behavior through mother-to-child hostility. For genetically unrelated mothers, effects were apparent only for maternal antisocial behavior on child antisocial behavior through mother-to-child hostility. For both genetically related and genetically unrelated fathers and children, interparental conflict and paternal antisocial behavior influenced child antisocial behavior through father-to-child hostility. Effects of parental anxiety symptoms on child antisocial behavior were apparent only for genetically related mothers and children. Results are discussed with respect to the relative role of passive genotype-environment correlation as a possible confounding factor underlying family process influences on childhood psychopathology.

  9. Odor aversion of multiple chemical sensitivities: recommendation for a name change and description of successful behavioral medicine treatment.

    Science.gov (United States)

    Amundsen, M A; Hanson, N P; Bruce, B K; Lantz, T D; Schwartz, M S; Lukach, B M

    1996-08-01

    Patients with odor-triggered symptoms, meeting the case definition of multiple chemical sensitivities (MCS), continue to be seen in our institution and other health science centers [Amundsen, Mayo Clinic Dept. Intern. Med. Newslett. 9(1) (1986)]. The term MCS, unfortunately, feeds the thesis that symptoms are allergic-immune system in origin, a theory that has not withstood scientific scrutiny [American College of Physicians, Ann. Intern. Med. 111, 168-178 (1989); Terr, Ann. Intern. Med. 119, 163-164 (1993)]. It has been proposed that some of these cases may be examples of classical (Pavlovian) conditioning: many MCS patients meet diagnostic criteria for psychiatric illnesses, especially mood, anxiety, and somatoform disorders. Attention is turning to the complex relationship between olfactory stimulation, memory, and mood (psyche) in an attempt to understand why some individuals develop odor aversion symptoms and how to best manage these, frequently, severely disabled patients. Two subjects with typical odor-triggered symptoms have been treated, using behavioral medicine techniques, with marked improvement in both cases. The term "odor aversion" is proposed rather than MCS to describe patients with these symptoms.

  10. Identification of genetic modifiers of behavioral phenotypes in serotonin transporter knockout rats

    Directory of Open Access Journals (Sweden)

    Nijman Isaäc J

    2010-05-01

    Full Text Available Abstract Background Genetic variation in the regulatory region of the human serotonin transporter gene (SLC6A4 has been shown to affect brain functionality and personality. However, large heterogeneity in its biological effects is observed, which is at least partially due to genetic modifiers. To gain insight into serotonin transporter (SERT-specific genetic modifiers, we studied an intercross between the Wistar SERT-/- rat and the behaviorally and genetically divergent Brown Norway rat, and performed a QTL analysis. Results In a cohort of >150 intercross SERT-/- and control (SERT+/+ rats we characterized 12 traits that were previously associated with SERT deficiency, including activity, exploratory pattern, cocaine-induced locomotor activity, and abdominal and subcutaneous fat. Using 325 genetic markers, 10 SERT-/--specific quantitative trait loci (QTLs for parameters related to activity and exploratory pattern (Chr.1,9,11,14, and cocaine-induced anxiety and locomotor activity (Chr.5,8 were identified. No significant QTLs were found for fat parameters. Using in silico approaches we explored potential causal genes within modifier QTL regions and found interesting candidates, amongst others, the 5-HT1D receptor (Chr. 5, dopamine D2 receptor (Chr. 8, cannabinoid receptor 2 (Chr. 5, and genes involved in fetal development and plasticity (across chromosomes. Conclusions We anticipate that the SERT-/--specific QTLs may lead to the identification of new modulators of serotonergic signaling, which may be targets for pharmacogenetic and therapeutic approaches.

  11. Infusion of low dose glyceryl trinitrate has no consistent effect on burrowing behavior, running wheel activity and light sensitivity in female rats

    DEFF Research Database (Denmark)

    Christensen, Sarah Louise T; Petersen, Steffen; Sørensen, Dorte Bratbo

    2016-01-01

    Introduction: Glyceryl trinitrate induces headache during infusion to man and migraine patients develop an additional migraine attack a few hours after the infusion. Recently, we have moved this model into rat with the intention of developing an animal model predictive of migraine therapy....... In the current paper we have studied the effect of glyceryl trinitrate infusion on three different rat behaviors. Methods: The stability of burrowing behavior, running wheel activity and light sensitivity towards repeated testing was evaluated also with respect to estrous cycle. Finally, the effect of glyceryl...... trinitrate on these behaviors in female rats was observed. Results: Burrowing behavior and running wheel activity were stable in the individual rat between experiments. The burrowing behavior was significantly affected by the stage of estrous cycle. The other assays were stable throughout the cycle. None...

  12. MODAFINIL INDUCES RAPID-ONSET BEHAVIORAL SENSITIZATION AND CROSS-SENSTIZATION WITH COCAINE IN MICE: IMPLICATIONS FOR THE ADDICTIVE POTENTIAL OF MODAFINIL

    Directory of Open Access Journals (Sweden)

    Raphael Wuo-Silva

    2016-11-01

    Full Text Available There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross-sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16 mg/kg, 32 mg/kg, and 64 mg/kg, administered 4h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine, in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.

  13. The effect of chronic stress in pregnant mothers on the responsiveness to morphine in mice: a behavioral sensitization study

    Directory of Open Access Journals (Sweden)

    zahra Nazari

    2008-10-01

    Full Text Available Nazari Z1, Sahraei H2, Sadoughi M3 1. MSc in Animal Biology (physiology trend, Lorestan Education Organization, Khorramabad, Iran 2. Assistant Professor, Department of Physiology, Faculty of Medicine, Baghyatallah University of Mesical Sciences, Tehran, Iran 3. Assistant Professor, Department of Biology, Faculty of Science, North Tehran Branch, Islamic Azad University, Tehran, Iran Abstract Background: The mechanisms which are plots for individuals willing to use Morphine are not yet recognized. Carried out researches indicated that tendency to narcotics is increased during stress or after it. In this research we studied the desire change of the second generation to morphine using induced restraint stress which is a kind of behavioral sensitization. Materials and methods: This research was a kind of experimental interferer. At first mice were crossed after insuring about their pregnancy, Sub stress was put on them using special instruments. Some of the embryos head was cut to be studied histologically. After maturing their embryos in order to clarify their left and right handedness to be studied using T-Maze and they were compared with the control group. In order to find the effectiveness of the administrated acute morphine, five groups of stressed and non-stressed were chosen Both groups were divided into five: a control (without being injected, saline, Morphine 1 mg/kg, morphine 10 mg/kg and morphine 50 mg/kg. They were studied. Movement measuring done after being injected by open filled. Mentioned groups in the previous experiment, In order to determine their previous induced sensitization, were reexamined 48 hours after being injected 1 mg/kg morphine. Results: Findings showed that the tissue thickness on the frontal cortex in stressed group was less than the control group (p<0.01 And also the number of stressed right handedness in males was less, but the number of left handedness in female ones was higher. Injection low dose morphine in

  14. Behaviorism

    National Research Council Canada - National Science Library

    Moore, J

    2011-01-01

    .... Watson proposed an alternative: classical S-R behaviorism. According to Watson, behavior was a subject matter in its own right, to be studied by the observational methods common to all sciences...

  15. Sensitization of dural afferents underlies migraine-related behavior following meningeal application of interleukin-6 (IL-6

    Directory of Open Access Journals (Sweden)

    Yan Jin

    2012-01-01

    contribute to migraine-related pain behavior in vivo. These data provide a cellular mechanism by which IL-6 in the meninges causes sensitization of dural afferents therefore contributing to the pathogenesis of migraine headache.

  16. Ifenprodil attenuates the acquisition and expression of methamphetamine-induced behavioral sensitization and activation of Ras-ERK1/2 cascade in the caudate putamen.

    Science.gov (United States)

    Li, Lu; Qiao, Chuchu; Chen, Gang; Qian, Hongyan; Hou, Ying; Li, Tao; Liu, Xinshe

    2016-10-29

    Chronic discontinuous use of many psychomotor stimulants leads to behavioral sensitization and, owing to it shares common mechanisms with relapse, most researchers use its animal model to explore the neurobiological mechanisms of addiction. Recent studies have proved that N-methyl-d-aspartate receptors (NMDARs) are implicated in psychomotor stimulant-induced behavioral sensitization. However, the function of GluN2B-containing NMDARs and their potential downstream cascade(s) in the acquisition and expression of behavioral sensitization to methamphetamine (METH) have not been explored. In this study, 2.5, 5, and 10mg/kg ifenprodil, the specific inhibitor of GluN2B, was used to explore the function of these receptors in distinct phases of behavioral sensitization to METH in mice. Then, using western blot, Ras, pERK1/2/ERK1/2, and ΔFosB levels in the prefrontal cortex (PFc), nucleus accumbens (NAc), and caudate putamen (CPu) were detected. Behavioral results showed that low-dose ifenprodil attenuated the acquisition and expression of behavioral sensitization to METH significantly. Western blot analysis revealed that pre-injection of low-dose ifenprodil in the acquisition markedly attenuated METH-induced ascent of Ras, pERK1/2/ERK1/2, and ΔFosB protein levels in the CPu. However, pre-treatment in the expression only affected the alterations of Ras and pERK1/2/ERK1/2 levels in the CPu. Moreover, chronic METH administration increased pERK1/2/ERK1/2 level in the NAc. In conclusion, GluN2B-containing NMDARs contribute to both the acquisition and expression of behavioral sensitization to METH in mice. Furthermore, the acquisition phase might be mediated by the Ras-ERK1/2-ΔFosB cascade in the CPu while the expression phase may be regulated by the Ras-ERK1/2 cascade in the CPu.

  17. Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing.

    Science.gov (United States)

    Hennessy, Michael B; Chun, Katie; Capitanio, John P

    2017-02-01

    Psychosocial stressors appear to promote the onset of depressive illness through activation and sensitization of inflammatory mechanisms. Here, adult male rhesus monkeys brought from large outdoor social groups to indoor housing for 8 days reliably exhibited a hunched, depressive-like posture. When rehoused indoors a second 8 days about 2 weeks later, monkeys housed alone, but not those with an affiliative partner, showed sensitization of the depressive-like hunched posture. Housing indoors also affected circulating pro-inflammatory cytokines: IL-1β showed increased responsiveness to immune challenge, and IL-1β and TNF-α showed reduced suppression by dexamethasone. Sensitivity of the anti-inflammatory cytokine IL-10 to immune challenge exhibited a relative increase from the first to the second round of indoor housing in animals housed in pairs, and a relative decrease in animals housed alone. Cytokine levels during indoor housing were positively correlated with duration of depressive-like behavior. Plasma cortisol levels increased but did not differentiate housing conditions or rounds. Results demonstrate a rapid induction and sensitization of depressive-like behavior to indoor individual housing, social buffering of sensitization, and associated inflammatory responses. This paradigm may provide a practical nonhuman primate model for examining inflammatory-mediated consequences of psychosocial stressors on depression and possible social buffering of these effects.

  18. Behaviorism

    Science.gov (United States)

    Moore, J.

    2011-01-01

    Early forms of psychology assumed that mental life was the appropriate subject matter for psychology, and introspection was an appropriate method to engage that subject matter. In 1913, John B. Watson proposed an alternative: classical S-R behaviorism. According to Watson, behavior was a subject matter in its own right, to be studied by the…

  19. Behaviorism

    Science.gov (United States)

    Moore, J.

    2011-01-01

    Early forms of psychology assumed that mental life was the appropriate subject matter for psychology, and introspection was an appropriate method to engage that subject matter. In 1913, John B. Watson proposed an alternative: classical S-R behaviorism. According to Watson, behavior was a subject matter in its own right, to be studied by the…

  20. Comparing non-specific physical symptoms in environmentally sensitive patients : Prevalence, duration, functional status and illness behavior

    NARCIS (Netherlands)

    Baliatsas, Christos; Van Kamp, Irene; Hooiveld, Mariette; Yzermans, Joris; Lebret, Erik

    2014-01-01

    Objective: Little is known about the potential clinical relevance of non-specific physical symptoms (NSPS) reported by patients with self-reported environmental sensitivities. This study aimed to assess NSPS in people with general environmental sensitivity (GES) and idiopathic environmental intolera

  1. Comparing non-specific physical symptoms in environmentally sensitive patients: prevalence, duration, functional status and illness behavior.

    NARCIS (Netherlands)

    Baliatsas, C.; Kamp, I. van; Hooiveld, M.; Yzermans, J.; Lebret, E.

    2014-01-01

    Objective: Little is known about the potential clinical relevance of non-specific physical symptoms (NSPS) reported by patients with self-reported environmental sensitivities. This study aimed to assess NSPS in people with general environmental sensitivity (GES) and idiopathic environmental intolera

  2. Life history trade-offs and behavioral sensitivity to testosterone: an experimental test when female aggression and maternal care co-occur.

    Directory of Open Access Journals (Sweden)

    Kimberly A Rosvall

    Full Text Available Research on male animals suggests that the hormone testosterone plays a central role in mediating the trade-off between mating effort and parental effort. However, the direct links between testosterone, intrasexual aggression and parental care are remarkably mixed across species. Previous attempts to reconcile these patterns suggest that selection favors behavioral insensitivity to testosterone when paternal care is essential to reproductive success and when breeding seasons are especially short. Females also secrete testosterone, though the degree to which similar testosterone-mediated trade-offs occur in females is much less clear. Here, I ask whether testosterone mediates trade-offs between aggression and incubation in females, and whether patterns of female sensitivity to testosterone relate to female life history, as is often the case in males. I experimentally elevated testosterone in free-living, incubating female tree swallows (Tachycineta bicolor, a songbird with a short breeding season during which female incubation and intrasexual aggression are both essential to female reproductive success. Testosterone-treated females showed significantly elevated aggression, reduced incubation temperatures, and reduced hatching success, relative to controls. Thus, prolonged testosterone elevation during incubation was detrimental to reproductive success, but females nonetheless showed behavioral sensitivity to testosterone. These findings suggest that the relative importance of both mating effort and parental effort may be central to understanding patterns of behavioral sensitivity in both sexes.

  3. Foster children's attachment behavior and representation: Influence of children's pre-placement experiences and foster caregiver's sensitivity.

    Science.gov (United States)

    Bovenschen, Ina; Lang, Katrin; Zimmermann, Janin; Förthner, Judith; Nowacki, Katja; Roland, Inga; Spangler, Gottfried

    2016-01-01

    Although the majority of foster children have been exposed to early adversity in their biological families and have experienced one or more disruptions of attachment relationships, most studies surprisingly found foster children to be as securely attached as children in low-risk samples. However, attention has been paid almost exclusively to attachment formation in young children up to two years of age, and the majority of studies solely investigated attachment behavior whereas few is known about foster children's representations about attachment relationships. To extend findings on attachment in foster children and its predictors, our study examined both attachment behavior and representations in foster children aged between 3 and 8 years. Diverse potential predictors including child variables, birth parents' variables, pre-placement experiences, and foster caregiver's behavior were included in the analyses. Results revealed that foster children showed both lower attachment security and higher disorganization scores than children in low-risk samples. Attachment behavior and representation were found to be widely independent from each other. Different factors contributed to attachment behavior and representation: whereas foster children's attachment behavior was mainly influenced by foster parents' behavior, pre-placement experiences did predict hyperactivation and disorganization on the representational level. The results indicate that, when intervening with foster families, it seems crucial to focus not exclusively on the promotion of secure attachment behavior but also to develop interventions enhancing secure and organized attachment representations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Neuropeptide s alters anxiety but not depression-like behaviors in the flinders sensitive line rats, a genetic animal model

    DEFF Research Database (Denmark)

    Mathe, A.; Wegener, Gregers; Finger, B.

    2010-01-01

    Background: Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behavior in rodents. However, little knowledge is available to what extent the NPS system is involved in depression-related behaviors. The aim of the present work was to characterize ...

  5. A Time of Change: Behavioral and Neural Correlates of Adolescent Sensitivity to Appetitive and Aversive Environmental Cues

    Science.gov (United States)

    Somerville, Leah H.; Jones, Rebecca M.; Casey, B. J.

    2010-01-01

    Adolescence is a developmental period that entails substantial changes in affective and incentive-seeking behavior relative to both childhood and adulthood, including a heightened propensity to engage in risky behaviors and experience persistent negative and labile mood states. This review discusses the emotional and incentive-driven behavioral…

  6. Effect of drug physicochemical properties on drug release and their relationship with drug skin permeation behaviors in hydroxyl pressure sensitive adhesive.

    Science.gov (United States)

    Liu, Chao; Quan, Peng; Fang, Liang

    2016-10-10

    The aim of this study was to investigate the influence of drug physicochemical properties on drug release behaviors and their relationship with skin permeation behaviors, which provided transdermal enhancement strategies for the design of transdermal drug delivery system. Six model drugs with different physicochemical properties were selected and hydroxyl pressure sensitive adhesive (PSA) was synthesized. Horizontal diffusion cell was used to evaluate drug release and skin permeation behaviors. The relationship between physicochemical properties and release behaviors was conducted with regression analysis. Release behavior of 0.25% drug loading was linear related with polar surface area, which represented the hydrogen bond. Release behavior of 2.0% drug loading was dependent on the polarizability and log P, which represented dipole-dipole interaction and lipophilicity, respectively. According to the results of Fourier transform infrared spectroscopy, it was inferred that hydrogen bond was limited in controlling release of drug due to the limited quantity of bonding site, thus dipole-dipole interaction and log P became dominate control factors. Combining the drug release study and drug skin permeation study, it was concluded that drugs with different physicochemical properties should be applied with different transdermal enhancement strategies, which was useful for the design of transdermal drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Stress-induced enhancement of fear conditioning and sensitization facilitates extinction-resistant and habituation-resistant fear behaviors in a novel animal model of posttraumatic stress disorder.

    Science.gov (United States)

    Corley, Michael J; Caruso, Michael J; Takahashi, Lorey K

    2012-01-18

    Posttraumatic stress disorder (PTSD) is characterized by stress-induced symptoms including exaggerated fear memories, hypervigilance and hyperarousal. However, we are unaware of an animal model that investigates these hallmarks of PTSD especially in relation to fear extinction and habituation. Therefore, to develop a valid animal model of PTSD, we exposed rats to different intensities of footshock stress to determine their effects on either auditory predator odor fear extinction or habituation of fear sensitization. In Experiment 1, rats were exposed to acute footshock stress (no shock control, 0.4 mA, or 0.8 mA) immediately prior to auditory fear conditioning training involving the pairing of auditory clicks with a cloth containing cat odor. When presented to the conditioned auditory clicks in the next 5 days of extinction testing conducted in a runway apparatus with a hide box, rats in the two shock groups engaged in higher levels of freezing and head out vigilance-like behavior from the hide box than the no shock control group. This increase in fear behavior during extinction testing was likely due to auditory activation of the conditioned fear state because Experiment 2 demonstrated that conditioned fear behavior was not broadly increased in the absence of the conditioned auditory stimulus. Experiment 3 was then conducted to determine whether acute exposure to stress induces a habituation resistant sensitized fear state. We found that rats exposed to 0.8 mA footshock stress and subsequently tested for 5 days in the runway hide box apparatus with presentations of nonassociative auditory clicks exhibited high initial levels of freezing, followed by head out behavior and culminating in the occurrence of locomotor hyperactivity. In addition, Experiment 4 indicated that without delivery of nonassociative auditory clicks, 0.8 mA footshock stressed rats did not exhibit robust increases in sensitized freezing and locomotor hyperactivity, albeit head out vigilance

  8. Hippocampus modulates the behaviorally-sensitizing effects of nicotine in a rat model of novelty-seeking: potential role for mossy fibers.

    Science.gov (United States)

    Bhatti, Amrinder S; Hall, Penny; Ma, Zhiyuan; Tao, Rui; Isgor, Ceylan

    2007-01-01

    Present experiments investigate interactions between a rat model of the novelty-seeking phenotype and psychomotor sensitization to nicotine (NIC) in adolescence, and the potential role of hippocampal mossy fibers in mediating the behaviorally-sensitizing effects of NIC. Outbred rats were phenotype-screened as high-responders (HR; locomotor reactivity to novelty score ranking in the upper third of the population) or low-responders (LR; locomotor reactivity to novelty score ranking in the lower third of the population). In Experiment 1, both phenotypes were trained with four NIC injections (at 3-d intervals on postnatal days 33-44), and lidocaine microinfusion was used to temporarily inactivate the hippocampal hilus at each NIC injection. Systemic saline and microinjection of artificial cerebral spinal fluid (CSF) were used as controls. During NIC training, lidocaine inactivation caused augmented locomotor response to NIC in HRs compared to LRs irrespective of injection days. Following 1 week of abstinence, all animals were challenged with a low dose of NIC. During challenge, previously NIC/CSF trained LRs and HRs were divided into two; one half receiving lidocaine inactivation of the hippocampal hilus and the other half receiving CSF control microinjection. Only HRs showed behavioral sensitization to the challenge dose of NIC, which was enhanced with lidocaine inactivation. In Experiment 2, a single NIC exposure was found sufficient to induce sensitization to the challenge dose of NIC in HRs, and concurrently an enlarged supra-pyramidal mossy fiber (SP-MF) terminal field. The increase in the SP-MF volume in HRs was greater with repeated NIC training. In both single and repeated NIC training cases, a significant positive morphobehavioral correlation was observed between challenge NIC-induced locomotion and the SP-MF terminal field volume. These findings suggest that the HR hippocampal mossy fibers are vulnerable to neuroadaptive alterations induced by NIC, which may

  9. Compulsive checking behavior of quinpirole-sensitized rats as an animal model of Obsessive-Compulsive Disorder(OCD: form and control

    Directory of Open Access Journals (Sweden)

    Bonura Carlo A

    2001-04-01

    Full Text Available Abstract Background A previous report showed that the open field behavior of rats sensitized to the dopamine agonist quinpirole satisfies 5 performance criteria for compulsive checking behavior. In an effort to extend the parallel between the drug-induced phenomenon and human obsessive-compulsive disorder (OCD, the present study investigated whether the checking behavior of quinpirole rats is subject to interruption, which is an attribute characteristic of OCD compulsions. For this purpose, the rat's home-cage was placed into the open field at the beginning or the middle of a 2-hr test. Results Introduction of the home-cage reduced checking behavior, as rats stayed inside the cage. After 40 min, checking resurfaced, as quinpirole rats exited the home-cage often. An unfamiliar cage had no such effects on quinpirole rats or saline controls. Conclusions Checking behavior induced by quinpirole is not irrepressible but can be suspended. Results strengthen the quinpirole preparation as an animal model of OCD compulsive checking.

  10. Differences between the detonation behavior of emulsion explosives sensitized with glass or with polymeric micro-balloons

    Science.gov (United States)

    Mendes, R.; Ribeiro, J.; Plaksin, I.; Campos, J.; Tavares, B.

    2014-05-01

    The differences between the detonation behaviour of ammonium nitrate based emulsion explosives sensitized with polymeric and those sensitized with glass micro-balloons is presented and discussed. Expancel® are hollow polymeric micro-balloons that contain a hydrocarbon gas. The mean particle size of these particles is 30 μm with a wall thickness of about 0.1 μm. The detonation velocity and the failure diameter of the emulsion explosive sensitized with different amounts of these particles have been measured in cylindrical charges by optical fibers. The detonation velocity demonstrates non-linear behaviour in relation to density and reaches the maximum value for a density lower than that of the matrix. The detonation fails when the density approaches that of the matrix. The detonation in the emulsion explosives extinguishes itself at a porosity value that seems to be independent from the nature of the sensitizing agent. For low densities, the detonation velocity is almost independent of the charge diameter, and is close to the values predicted by BKW equation of state.

  11. The sensitivity of lateral line receptors and their role in the behavior of Mexican blind cavefish (Astyanax mexicanus)

    NARCIS (Netherlands)

    Yoshizawa, Masato; Jeffery, William R; van Netten, Sietse M; McHenry, Matthew J

    2014-01-01

    The characid fish species Astyanax mexicanus offers a classic comparative model for the evolution of sensory systems. Populations of this species evolved in caves and became blind while others remained in streams (i.e. surface fish) and retained a functional visual system. The flow-sensitive lateral

  12. [Acoustically guided behavior in the early ontogeny of the long-eared owl: the development of hearing sensitivity].

    Science.gov (United States)

    Golubeva, T V

    1996-01-01

    The development of hearing sensitivity was studied in 15 nestlings and 7 adult long eared owls by cochlear recording potentials. The dynamic of frequency threshold characteristics of cochlear microphonic, action potential of cochlear nerve, and electromyogram of reflectory contraction of middle ear muscle were followed from the 1st to 40 day posthatching. The upper limit of hearing determined by cochlear microphonic, was about 3 kHz on the 1st day after hatching, 7 kHz on the 6th day, and 10 kHz on the 11th. Within 11 days after hatching the low-frequency range of higher sensitivity was revealed (with the maximum at 0.5 kHz), which was the same as that of monotonic signals effective for stimulation of the feeding reaction. The middle frequency range of higher sensitivity corresponded to the spectrum of own vocalization of the nestlings. During the period of formation of the patterned vision there was a delay in development of low- and middle-frequency sensitivity of cochlear microphonic while the high-frequency thresholds continued to decrease. After this period the guiding stimulation for eliciting feeding reaction changes from the auditory for the visual. The action potential of the cochlear nerve could be recorded from the 6th day simultaneously with the appearance of locating head movements and the reflectory contraction of the middle ear muscle.

  13. The sensitivity of lateral line receptors and their role in the behavior of Mexican blind cavefish (Astyanax mexicanus)

    NARCIS (Netherlands)

    Yoshizawa, Masato; Jeffery, William R; van Netten, Sietse M; McHenry, Matthew J

    2014-01-01

    The characid fish species Astyanax mexicanus offers a classic comparative model for the evolution of sensory systems. Populations of this species evolved in caves and became blind while others remained in streams (i.e. surface fish) and retained a functional visual system. The flow-sensitive lateral

  14. Executive Functions and Child Problem Behaviors Are Sensitive to Family Disruption: A Study of Children of Mothers Working Overseas

    Science.gov (United States)

    Hewage, Chandana; Bohlin, Gunilla; Wijewardena, Kumudu; Lindmark, Gunilla

    2011-01-01

    Mothers in Sri Lanka are increasingly seeking overseas employment, resulting in disruption of the childcare environment. The present study was designed to evaluate the effects of maternal migration on executive function (EF) and behavior, thereby also contributing to the scientific understanding of environmental effects--or more specifically…

  15. Are infants differentially sensitive to parenting? Early maternal care, DRD4 genotype and externalizing behavior during adolescence.

    Science.gov (United States)

    Nikitopoulos, Jörg; Zohsel, Katrin; Blomeyer, Dorothea; Buchmann, Arlette F; Schmid, Brigitte; Jennen-Steinmetz, Christine; Becker, Katja; Schmidt, Martin H; Esser, Günter; Brandeis, Daniel; Banaschewski, Tobias; Laucht, Manfred

    2014-12-01

    Insensitive and unresponsive caregiving during infancy has been linked to externalizing behavior problems during childhood and adolescence. The 7-repeat (7r) allele of the dopamine D4 receptor (DRD4) gene has meta-analytically been associated with a heightened susceptibility to adverse as well as supportive environments. In the present study, we examined long-term effects of early maternal care, DRD4 genotype and the interaction thereof on externalizing and internalizing psychopathology during adolescence. As part of an ongoing epidemiological cohort study, early maternal care was assessed at child's age 3 months during a nursing and playing situation. In a sample of 296 offspring, externalizing and internalizing symptoms were assessed using a psychiatric interview conducted at age 15 years. Parents additionally filled out a questionnaire on their children's psychopathic behaviors. Results indicated that adolescents with the DRD4 7r allele who experienced less responsive and stimulating early maternal care exhibited more symptoms of ADHD and CD/ODD as well as higher levels of psychopathic behavior. In accordance with the hypothesis of differential susceptibility, 7r allele carriers showed fewer ADHD symptoms and lower levels of psychopathic behavior when exposed to especially beneficial early caregiving. In contrast, individuals without the DRD4 7r allele proved to be insensitive to the effects of early maternal care. This study replicates earlier findings with regard to an interaction between DRD4 genotype and early caregiving on externalizing behavior problems in preschoolers. It is the first one to imply continuity of this effect until adolescence. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Blockade of Serotonin 5-HT2A Receptors Suppresses Behavioral Sensitization and Naloxone-Precipitated Withdrawal Symptoms in Morphine-Treated Mice

    Science.gov (United States)

    Pang, Gang; Wu, Xian; Tao, Xinrong; Mao, Ruoying; Liu, Xueke; Zhang, Yong-Mei; Li, Guangwu; Stackman, Robert W.; Dong, Liuyi; Zhang, Gongliang

    2016-01-01

    The increasing prescription of opioids is fueling an epidemic of addiction and overdose deaths. Morphine is a highly addictive drug characterized by a high relapse rate – even after a long period of abstinence. Serotonin (5-HT) neurotransmission participates in the development of morphine dependence, as well as the expression of morphine withdrawal. In this study, we examined the effect of blockade of 5-HT2A receptors (5-HT2ARs) on morphine-induced behavioral sensitization and withdrawal in male mice. 5-HT2AR antagonist MDL 11,939 (0.5 mg/kg, i.p.) suppressed acute morphine (5.0 mg/kg, s.c.)-induced increase in locomotor activity. Mice received morphine (10 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of morphine (10 mg/kg) was administered to induce the expression of behavioral sensitization. MDL 11,939 (0.5 mg/kg, i.p.) pretreatment suppressed the expression of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. MDL 11,939 (0.5 mg/kg, i.p.) prevented naloxone-precipitated withdrawal in morphine-dependent mice on day 7. Moreover, chronic morphine treatment increased 5-HT2AR protein level and decreased the phosphorylation of extracellular signal-regulated kinases in the prefrontal cortex. Together, these results by the first time demonstrate that 5-HT2ARs modulate opioid dependence and blockade of 5-HT2AR may represent a novel strategy for the treatment of morphine use disorders. Highlights (i) Blockade of 5-HT2A receptors suppresses the expression of morphine-induced behavioral sensitization. (ii) Blockade of 5-HT2A receptors suppresses naloxone-precipitated withdrawal in morphine-treated mice. (iii) Chronic morphine exposure induces an increase in 5-HT2A receptor protein level and a decrease in ERK protein phosphorylation in prefrontal cortex. PMID:28082900

  17. Behavioral Resilience and Sensitivity to Locally Restricted Cortical Migration Deficits Induced by In Utero Knockdown of Disabled-1 in the Adult Rat.

    Science.gov (United States)

    Vomund, Sandra; de Souza Silva, M Angelica; Huston, Joseph P; Korth, Carsten

    2017-03-01

    Irregular neuronal migration plays a causal role in mental illnesses such as schizophrenia and autism, but the very nature of the migration deficits necessary to evoke adult behavioral changes is unknown. Here, we used in utero electroporation (IUE) in rats to induce a locally restricted, cortical migration deficit by knockdown of disabled-1 (Dab1), an intracellular converging point of the reelin pathway. After birth, selection of successfully electroporated rats by detection of in vivo bioluminescence of a simultaneously electroporated luciferase gene correlated to and was thus predictive to the number of electroporated neurons in postmortem histochemistry at 6 months of age. Rat neurons silenced for Dab1 did not migrate properly and their number surprisingly decreased after E22. Behavioral tests at adult ages (P180) revealed increased sensitivity to amphetamine as well as decreased habituation, but no deficits in memory tasks or motor functions. The data suggest that even subtle migration deficits involving only ten-thousands of cortical neurons during neurodevelopment can lead to lasting behavioral and neuronal changes into adulthood in some very specific behavioral domains. On the other hand, the lack of effects on various memory-related tasks may indicate resilience and plasticity of cognitive functions critical for survival under these specific conditions. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Light-Emitting Diode Phototherapy Reduces Nocifensive Behavior Induced by Thermal and Chemical Noxious Stimuli in Mice: Evidence for the Involvement of Capsaicin-Sensitive Central Afferent Fibers.

    Science.gov (United States)

    Pigatto, Glauce Regina; Coelho, Igor Santos; Aquino, Rosane Schenkel; Bauermann, Liliane Freitas; Santos, Adair Roberto Soares

    2017-07-01

    Low-intensity phototherapy using light fonts, like light-emitting diode (LED), in the red to infrared spectrum is a promising alternative for the treatment of pain. However, the underlying mechanisms by which LED phototherapy reduces acute pain are not yet well understood. This study investigated the analgesic effect of multisource LED phototherapy on the acute nocifensive behavior of mice induced by thermal and chemical noxious stimuli. The involvement of central afferent C fibers sensitive to capsaicin in this effect was also investigated. Mice exposed to multisource LED (output power 234, 390, or 780 mW and power density 10.4, 17.3, and 34.6 mW/cm(2), respectively, from 10 to 30 min of stimulation with a wavelength of 890 nm) showed rapid and significant reductions in formalin- and acetic acid-induced nocifensive behavior. This effect gradually reduced but remained significant for up to 7 h after LED treatment in the last model used. Moreover, LED (390 mW, 17.3 mW/cm(2)/20 min) irradiation also reduced nocifensive behavior in mice due to chemical [endogenous (i.e., glutamate, prostaglandins, and bradykinin) or exogenous (i.e., formalin, acetic acid, TRPs and ASIC agonist, and protein kinase A and C activators)] and thermal (hot plate test) stimuli. Finally, ablating central afferent C fibers abolished LED analgesia. These experimental results indicate that LED phototherapy reduces the acute painful behavior of animals caused by chemical and thermal stimuli and that LED analgesia depends on the integrity of central afferent C fibers sensitive to capsaicin. These findings provide new information regarding the underlying mechanism by which LED phototherapy reduces acute pain. Thus, LED phototherapy may be an important tool for the management of acute pain.

  19. Synthesis, characterization, and swelling behaviors of salt-sensitive maize bran-poly(acrylic acid) superabsorbent hydrogel.

    Science.gov (United States)

    Zhang, Mingyue; Cheng, Zhiqiang; Zhao, Tianqi; Liu, Mengzhu; Hu, Meijuan; Li, Junfeng

    2014-09-01

    A novel composite hydrogel was prepared via UV irradiation copolymerization of acrylic acid and maize bran (MB) in the presence of composite initiator (2,2-dimethoxy-2-phenylacetophenone and ammonium persulfate) and cross-linker (N,N'-methylenebis(acrylamide)). Under the optimized conditions, maize bran-poly(acrylic acid) was obtained (2507 g g(-1) in distilled water and 658 g g(-1) in 0.9 wt % NaCl solution). Effects of granularity, salt concentration, and various cations and anions on water absorbency were investigated. It was found that swelling was extremely sensitive to the ionic strength and cation and anion type. Swelling kinetics and water diffusion mechanism in distilled water were also discussed. Moreover, the product showed excellent water retention capability under the condition of high temperature or high pressure. The salt sensitivity, good water absorbency, and excellent water retention capability of the hydrogels give this intelligentized polymer wide potential applications.

  20. Characterization of process-oriented hydrologic model behavior with temporal sensitivity analysis for flash floods in Mediterranean catchments

    Directory of Open Access Journals (Sweden)

    P. A. Garambois

    2013-06-01

    Full Text Available This paper presents a detailed analysis of 10 flash flood events in the Mediterranean region using the distributed hydrological model MARINE. Characterizing catchment response during flash flood events may provide new and valuable insight into the dynamics involved for extreme catchment response and their dependency on physiographic properties and flood severity. The main objective of this study is to analyze flash-flood-dedicated hydrologic model sensitivity with a new approach in hydrology, allowing model outputs variance decomposition for temporal patterns of parameter sensitivity analysis. Such approaches enable ranking of uncertainty sources for nonlinear and nonmonotonic mappings with a low computational cost. Hydrologic model and sensitivity analysis are used as learning tools on a large flash flood dataset. With Nash performances above 0.73 on average for this extended set of 10 validation events, the five sensitive parameters of MARINE process-oriented distributed model are analyzed. This contribution shows that soil depth explains more than 80% of model output variance when most hydrographs are peaking. Moreover, the lateral subsurface transfer is responsible for 80% of model variance for some catchment-flood events' hydrographs during slow-declining limbs. The unexplained variance of model output representing interactions between parameters reveals to be very low during modeled flood peaks and informs that model-parsimonious parameterization is appropriate to tackle the problem of flash floods. Interactions observed after model initialization or rainfall intensity peaks incite to improve water partition representation between flow components and initialization itself. This paper gives a practical framework for application of this method to other models, landscapes and climatic conditions, potentially helping to improve processes understanding and representation.

  1. Planarians in pharmacology: parthenolide is a specific behavioral antagonist of cocaine in the planarian Girardia tigrina.

    Science.gov (United States)

    Pagán, Oné R; Baker, Debra; Deats, Sean; Montgomery, Erica; Tenaglia, Matthew; Randolph, Clinita; Kotturu, Dharini; Tallarida, Christopher; Bach, Daniel; Wilk, Galia; Rawls, Scott; Raffa, Robert B

    2012-01-01

    Planarians are traditional animal models in developmental and regeneration biology. Recently, these organisms are arising as vertebrate-relevant animal models in neuropharmacology. Using an adaptation of published behavioral protocols, we have described the alleviation of cocaine-induced planarian seizure-like movements (pSLM) by a naturally-occurring sesquiterpene lactone, parthenolide. Interestingly, parthenolide does not prevent the expression of pSLM induced by amphetamines; in vertebrates, amphetamines interact with the same protein target as cocaine. Parthenolide is also unable to prevent pSLM elicited by the cholinergic com-pounds nicotine and cytisine or by the glutamatergic agents L- or D- glutamic acid or NMDA. Thus, we conclude that parthenolide is a specific anti-cocaine agent in this experimental organism.

  2. Numerical sensitivity analysis of welding-induced residual stress depending on variations in continuous cooling transformation behavior

    Science.gov (United States)

    Heinze, C.; Schwenk, C.; Rethmeier, M.; Caron, J.

    2011-06-01

    The usage of continuous cooling transformation (CCT) diagrams in numerical welding simulations is state of the art. Nevertheless, specifications provide limits in chemical composition of materials which result in different CCT behavior and CCT diagrams, respectively. Therefore, it is necessary to analyze the influence of variations in CCT diagrams on the developing residual stresses. In the present paper, four CCT diagrams and their effect on numerical calculation of residual stresses are investigated for the widely used structural steel S355J2 + N welded by the gas metal arc welding (GMAW) process. Rather than performing an arbitrary adjustment of CCT behavior, four justifiable data sets were used as input to the numerical calculation: data available in the Sysweld database, experimental data acquired through Gleeble dilatometry tests, and TTT/CCT predictions calculated from the JMatPro and Edison Welding Institute (EWI) Virtual Joining Portal software. The performed numerical analyses resulted in noticeable deviations in residual stresses considering the different CCT diagrams. Furthermore, possibilities to improve the prediction of distortions and residual stress based on CCT behavior are discussed.

  3. Pairing behavior and reproduction in Hyalella azteca as sensitive endpoints for detecting long-term consequences of pesticide pulses.

    Science.gov (United States)

    Pedersen, Signe; Palmqvist, Annemette; Thorbek, Pernille; Hamer, Mick; Forbes, Valery

    2013-11-15

    The aim of the present study was to examine acute and delayed effects of pulse exposure of the pyrethroid pesticide, permethrin, on precopulatory pairs of Hyalella azteca. Pairs of H. azteca were exposed to a single 1h pulse of different nominal concentrations of permethrin: 0, 0.3, 0.9 or 2.7 μg/L. During exposure, pairing behavior was observed, and during a 56 day post-exposure period the treatments were monitored for pairing behavior, survival and reproductive output. All permethrin-exposed pairs separated within minutes during exposure and shortly thereafter became immobile; however they regained mobility after transfer to clean water. The time to re-form pairs was significantly longer in all tested concentrations compared to the control, although all surviving pairs re-formed within the 56 day test period. Nevertheless not all pairs exposed to 0.9 and 2.7 μg/L reproduced. Furthermore the numbers of juveniles produced by pairs exposed to 0.9 and 2.7 μg/L, but not 0.3 μg/L, were lower throughout the entire post-exposure period compared to the control groups, and the total numbers of juveniles produced during 56 days were significantly lower in organisms exposed to 0.9 and 2.7 μg/L, but not 0.3 μg/L, compared to the control groups. The long-term effects of short-term exposure on reproductive behavior of pairs could potentially have consequences for the population dynamics of H. azteca. However, since individual-level responses can both overestimate and underestimate effects at the population level, appropriate population models are needed to reduce the uncertainty in extrapolating between these levels of biological organization.

  4. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants.

    Directory of Open Access Journals (Sweden)

    Katerina V Savelieva

    Full Text Available The neurotransmitter serotonin (5-HT plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2. We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO and Tph1/Tph2 double knockout (DKO mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders.

  5. Low Family Income and Behavior Problems in Norwegian Preschoolers: Is Child Emotionality a Marker for Sensitivity of Influence?

    Science.gov (United States)

    Bøe, Tormod; Hysing, Mari; Zachrisson, Henrik Daae

    2016-04-01

    Poor children have higher rates of mental health problems than more affluent peers, also in progressive welfare states such as Norway. Temperamental characteristics may render some children more sensitive to the adverse influence of poor economy. This study examined the direct associations between family income-to-needs and mental health and assessed moderation by early temperamental characteristics (i.e., emotionality). Using data from the Norwegian Mother and Child Cohort Study, associations between income-to-needs across children's first 3 years and internalizing and externalizing problems when children were 5 years old were examined. Differential sensitivity to family income-to-needs was assessed by investigating how emotionality, when children were one-and-a-half and 3 years old, moderated these associations. Significant main effects of income-to-needs and emotionality and a significant interaction effect between income-to-needs and emotionality were found for externalizing problems, but not for internalizing problems. Children in poor families with an emotionally reactive temperament had higher scores on externalizing problems when they were 5 compared with their less emotionally reactive peers.

  6. Dopamine D3 receptor knock-out mice exhibit increased behavioral sensitivity to the anxiolytic drug diazepam.

    Science.gov (United States)

    Leggio, Gian Marco; Micale, Vincenzo; Le Foll, Bernard; Mazzola, Carmen; Nobrega, José N; Drago, Filippo

    2011-04-01

    Dopamine D(3) receptors (DRsD3) seem to have a pivotal role in mood disorders. Using the elevated plus maze (EPM) and the novelty-induced grooming test (NGT), we assessed the responses of DRD3-deficient (D(3)(-/-)) mice to the acute treatment (different testing time) with the anxiolytic drug, diazepam. D(3)(-/-) mice treated with diazepam (0.1 or 0.5mg/kg) exhibited a better behavioral response in the EPM than their wild type (WT). Furthermore, in D(3)(-/-) mice, but not in WT, 1mg/kg diazepam induced anxiolytic effects at all testing times. The contribution of DRsD3 in the anxiolytic effects of diazepam was confirmed by similar results obtained in EPM by using the selective DRD3 antagonist U99194A (10mg/kg) in combination with diazepam, in WT animals. D(3)(-/-) mice treated with diazepam (all doses), also showed a decrease in grooming behavior. However, the [(3)H]flunitrazepam autoradiographic analysis revealed no significant changes in D(3)(-/-) mice compared to WT, suggesting that if γ-aminobutyric acid receptor GABA(A) changes are involved, they do not occur at the level of binding to benzodiazepine site. These data suggest that D(3)(-/-) mice exhibit low baseline anxiety levels and provide the evidence that the DRD3 is involved in the modulation of benzodiazepine anxiolytic effects.

  7. 3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner.

    Science.gov (United States)

    Meyer, E M; Tay, E T; Papke, R L; Meyers, C; Huang, G L; de Fiebre, C M

    1997-09-12

    The alpha7 nicotinic receptor agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB; GTS-21) was investigated for its ability to: (1) activate a variety of nicotinic receptor subtypes in Xenopus oocytes; (2) improve passive avoidance and spatial Morris water task performances in mecamylamine-sensitive manners in bilaterally nucleus basalis lesioned rats; and (3) elevate high-affinity [3H]acetylcholine (ACh) and high-affinity alpha-[125I]bungarotoxin binding in rat neocortex following 2 weeks of daily injections. DMXB (100 microM) activated alpha7 homo-oligomeric receptors, without significant activity at alpha2-, alpha3- and alpha4-containing subtypes. Mecamylamine blocked rat alpha7 receptors weakly if co-administered with agonist, but much more potently when pre-applied. Bilateral ibotenic acid lesions of the nucleus basalis interfered with passive avoidance and spatial memory-related behaviors. DMXB (0.5 mg/kg, i.p.) improved passive avoidance behavior in lesioned animals in a mecamylamine-sensitive manner. DMXB (0.5 mg/kg 15 min before each session) also improved performance in the training and probe components of the Morris water task. DMXB-induced improvement in the probe component but not the training phase was mecamylamine-sensitive. [3H]ACh binding was elevated after 14 days of daily i.p. injections with 0.2 mg/kg nicotine but not after 1 mg/kg DMXB. Neither drug elevated high-affinity alpha-[125I]bungarorotoxin binding over this interval.

  8. Behavioral measures of risk tasking, sensation seeking and sensitivity to reward may reflect different motivations for spicy food liking and consumption.

    Science.gov (United States)

    Byrnes, Nadia K; Hayes, John E

    2016-08-01

    Based on work a quarter century ago, it is widely accepted personality traits like sensation seeking are related to the enjoyment and intake of spicy foods; however, data supporting this belief is actually quite limited. Recently, we reported strong to moderate correlations between remembered spicy food liking and two personality traits measured with validated questionnaires. Here, participants consumed capsaicin-containing strawberry jelly to generate acute estimates of spicy food liking. Additionally, we used a laboratory-based behavioral measure of risk taking (the mobile Balloon Analogue Risk Task; mBART) to complement a range of validated self-report measures of risk-related personality traits. Present data confirm Sensation Seeking correlates with overall spicy meal liking and liking of the burn of a spicy meal, and extends prior findings by showing novel correlations with the liking of sampled stimuli. Other personality measures, including Sensitivity to Punishment (SP), Sensitivity to Reward (SR), and the Impulsivity and Risk Taking subscales of the DSM5 Personality Inventory (PID-5) did not show significant relationships with liking of spicy foods, either sampled or remembered. Our behavioral risk taking measure, the mBART, also failed to show a relationship with remembered or sampled liking. However, significant relationships were observed between reported intake of spicy foods and Sensitivity to Reward, and the Risk Taking subscale of the PID-5 (PID5-RT). Based on the observed patterns among various personality measures, and spicy food liking and intake, we propose that personality measures may exert their influence on intake of spicy food via different mechanisms. We also speculate that Sensation Seeking may reflect motivations for consuming spicy foods that are more intrinsic, while the motivations for eating spicy foods measured by SR and PID5-RT may be more extrinsic.

  9. Comportamiento de la sensibilidad dentinal en pacientes del municipio "10 de Octubre" Behavior of dentinal sensitivity in patients from the "10 de Octubre" municipality

    Directory of Open Access Journals (Sweden)

    Nereyda Riesgo Lobaina

    2010-03-01

    Full Text Available Se realizó un estudio descriptivo transversal con el objetivo de determinar el comportamiento de la sensibilidad dentinal en tres clínicas estomatológicas del municipio "10 de Octubre". Las variables estudiadas fueron: edad, sexo, factores predisponentes, grado del dolor, grupos de dientes examinados y tipo de retracción periodontal presente. Se encontraron 150 pacientes que presentaron 190 dientes afectados por sensibilidad dentinal. El sexo femenino fue el más representado, así como los grupos de edades más jóvenes. Se encontró que el grado 3 de dolor prevaleció y estuvo más relacionado con la recesión peridontal tipo III. La causa más frecuente de sensibilidad dentinal fue el cepillado dental.A cross-sectional and descriptive study was conducted to determine the behavior of dentinal sensitivity in patients of three Stomatology Clinics from "10 de Octubre" municipality. Study variable were: age, sex, predisposing factors, pain degree, groups of examined teeth and the type of periodontal retraction present. There were 150 patients with 190 teeth involved by dentinal sensitivity. Female sex was the more affected one, as well as the younger age groups. We found that 3 degree pain prevailed and that it was more related to type III periodontal recession. The more frequent cause of dentinal sensitivity was the dental brushing.

  10. Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: Pharmacological and behavioral genetics evidence

    Directory of Open Access Journals (Sweden)

    Jonathan eHollander

    2012-07-01

    Full Text Available Considerable evidence suggests that transmission at hypocretin-1 (orexin-1 receptors (Hcrt-R1 plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg dose-dependently decreased cocaine (0.5 mg/kg/infusion self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine, and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts.

  11. How great was the Great Oxidation Event? Observations from the behavior of redox-sensitive elements in Precambrian glacial tillites

    Science.gov (United States)

    Gaschnig, R. M.; Rudnick, R. L.; McDonough, W. F.

    2013-12-01

    The Great Oxidation Event (GOE) is considered a watershed event in the development of the Earth's biosphere, in which global atmospheric oxygen levels exceeded ~2 ppmv for the first time. This event occurred during the early Paleoproterozoic Huronian glacial interval and is defined by the disappearance of mass independent sulfur isotope fractionation. In the Huronian Supergroup in Ontario, this sulfur isotopic marker occurs between the lower two of the three glacial tillites present (Papineau et al., 2007). This implies that the youngest Huronian tillite (the Gowganda Formation) was deposited in a distinctively more oxic Earth surface environment. Here, we present data for redox sensitive transition metals in Precambrian glacial tillites, which indicate that oxic weathering of the continents remained insignificant in the immediate aftermath of the GOE, during the second half of the Huronian glaciation. Glacial tillites deposited around the world by continental ice sheets during the Mesoarchean (~2.9 Ga), Paleoproterozoic (~2.4-2.2 Ga), Neoproterozoic (~0.7-0.6 Ga), and Paleozoic (~0.3 Ga) were analyzed for their trace element compositions (n = 120). Mesoarchean and Paleoproterozoic tillites show significant differences from younger tillites in both absolute abundances of redox sensitive transition metals and abundances relative to elements with similar compatibilities. Transition metal abundances in all Mesoarchean and Paleoproterozoic tillites are either similar to or are higher than those in the average upper continental crust, whereas these elements are depleted in Neoproterozoic and younger tillites. Moreover, Mo, V and Cr are preferentially enriched in Mesoarchean and Paleoproterozoic tillites relative to elements of similar incompatibility, whereas a complementary depletion is seen in Neoproterozoic and younger tillites. We attribute these depletions of Mo, V, and Cr to their significantly enhanced solubility during weathering in the presence of an oxic

  12. Path Sensitization

    Institute of Scientific and Technical Information of China (English)

    赵著行; 闵应骅; 等

    1997-01-01

    For different delay models,the concept of sensitization can be very different.Traditonal concepts of sensitization cannot precisely describe circuit behavior when the input vectors change very fast.Using Boolean process aporoach,this paper presents a new definition of sensitization for arbitrary input waveforms.By this new concept it is found that if the inputs of a combinational circuit can change at any time,and each gate's delay varies within an interval (bounded gate delay model),then every path,which is not necessarily a single topological path,is sensitizable.From the experimental results it can be seen that,all nonsensitizable paths for traditional concepts actually can propagate transitions along them for some input waveforms.However,specified time between input transitions(STBIT) and minimum permissible pulse width(ε)are two major factors to make some paths non-sensitizable.

  13. Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

    Directory of Open Access Journals (Sweden)

    Dickenson Anthony H

    2009-02-01

    Full Text Available Abstract Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1 has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal

  14. Twins Early Development Study (TEDS): a genetically sensitive investigation of cognitive and behavioral development from childhood to young adulthood.

    Science.gov (United States)

    Haworth, Claire M A; Davis, Oliver S P; Plomin, Robert

    2013-02-01

    The Twins Early Development Study (TEDS) is a large longitudinal sample of twins born in England and Wales between 1994 and 1996. The focus of TEDS has been on cognitive and behavioral development, including difficulties in the context of normal development. TEDS began when multiple births were identified from birth records and the families were invited to take part in the study; 16,810 pairs of twins were originally enrolled in TEDS. More than 10,000 of these twin pairs remain enrolled in the study to date. DNA has been collected for more than 7,000 pairs, and genome-wide genotyping data for two million DNA markers are available for 3,500 individuals. The TEDS families have taken part in studies when the twins were aged 2, 3, 4, 7, 8, 9, 10, 12, 14, and 16 years of age. Data collection is currently underway to assess the adult destinations of the twins as they move from school to university and the workplace. Between January 2012 and December 2014, all of the TEDS twins will turn 18, and the study will transition to an adult sample. TEDS represents an outstanding resource for investigating the developmental effects of genes and environments on complex quantitative traits from childhood to young adulthood and beyond.

  15. Vulnerability or Sensitivity to the Environment? Methodological Issues, Trends, and Recommendations in Gene-Environment Interactions Research in Human Behavior.

    Science.gov (United States)

    Leighton, Caroline; Botto, Alberto; Silva, Jaime R; Jiménez, Juan Pablo; Luyten, Patrick

    2017-01-01

    Research on the potential role of gene-environment interactions (GxE) in explaining vulnerability to psychopathology in humans has witnessed a shift from a diathesis-stress perspective to differential susceptibility approaches. This paper critically reviews methodological issues and trends in this body of research. Databases were screened for studies of GxE in the prediction of personality traits, behavior, and mental health disorders in humans published between January 2002 and January 2015. In total, 315 papers were included. Results showed that 34 candidate genes have been included in GxE studies. Independent of the type of environment studied (early or recent life events, positive or negative environments), about 67-83% of studies have reported significant GxE interactions, which is consistent with a social susceptibility model. The percentage of positive results does not seem to differ depending on the gene studied, although publication bias might be involved. However, the number of positive findings differs depending on the population studied (i.e., young adults vs. older adults). Methodological considerations limit the ability to draw strong conclusions, particularly as almost 90% (n = 283/315) of published papers are based on samples from North America and Europe, and about 70% of published studies (219/315) are based on samples that were also used in other reports. At the same time, there are clear indications of methodological improvements over time, as is shown by a significant increase in longitudinal and experimental studies as well as in improved minimum genotyping. Recommendations for future research, such as minimum quality assessment of genes and environmental factors, specifying theoretical models guiding the study, and taking into account of cultural, ethnic, and lifetime perspectives, are formulated.

  16. Vulnerability or Sensitivity to the Environment? Methodological Issues, Trends, and Recommendations in Gene–Environment Interactions Research in Human Behavior

    Directory of Open Access Journals (Sweden)

    Caroline Leighton

    2017-06-01

    Full Text Available Research on the potential role of gene–environment interactions (GxE in explaining vulnerability to psychopathology in humans has witnessed a shift from a diathesis-stress perspective to differential susceptibility approaches. This paper critically reviews methodological issues and trends in this body of research. Databases were screened for studies of GxE in the prediction of personality traits, behavior, and mental health disorders in humans published between January 2002 and January 2015. In total, 315 papers were included. Results showed that 34 candidate genes have been included in GxE studies. Independent of the type of environment studied (early or recent life events, positive or negative environments, about 67–83% of studies have reported significant GxE interactions, which is consistent with a social susceptibility model. The percentage of positive results does not seem to differ depending on the gene studied, although publication bias might be involved. However, the number of positive findings differs depending on the population studied (i.e., young adults vs. older adults. Methodological considerations limit the ability to draw strong conclusions, particularly as almost 90% (n = 283/315 of published papers are based on samples from North America and Europe, and about 70% of published studies (219/315 are based on samples that were also used in other reports. At the same time, there are clear indications of methodological improvements over time, as is shown by a significant increase in longitudinal and experimental studies as well as in improved minimum genotyping. Recommendations for future research, such as minimum quality assessment of genes and environmental factors, specifying theoretical models guiding the study, and taking into account of cultural, ethnic, and lifetime perspectives, are formulated.

  17. Prediction of alcohol drinking in adolescents: Personality-traits, behavior, brain responses, and genetic variations in the context of reward sensitivity.

    Science.gov (United States)

    Heinrich, Angela; Müller, Kathrin U; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Papadopoulos, Dimitri; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Mann, Karl; Martinot, Jean-Luc; Paus, Tomáš; Pausova, Zdenka; Smolka, Michael; Ströhle, Andreas; Rietschel, Marcella; Flor, Herta; Schumann, Gunter; Nees, Frauke

    2016-07-01

    Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age=14.37) and again later (mean age=16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced.

  18. Generalized Anxiety Disorder and Social Anxiety Disorder, but Not Panic Anxiety Disorder, Are Associated with Higher Sensitivity to Learning from Negative Feedback: Behavioral and Computational Investigation.

    Science.gov (United States)

    Khdour, Hussain Y; Abushalbaq, Oday M; Mughrabi, Ibrahim T; Imam, Aya F; Gluck, Mark A; Herzallah, Mohammad M; Moustafa, Ahmed A

    2016-01-01

    Anxiety disorders, including generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic anxiety disorder (PAD), are a group of common psychiatric conditions. They are characterized by excessive worrying, uneasiness, and fear of future events, such that they affect social and occupational functioning. Anxiety disorders can alter behavior and cognition as well, yet little is known about the particular domains they affect. In this study, we tested the cognitive correlates of medication-free patients with GAD, SAD, and PAD, along with matched healthy participants using a probabilistic category-learning task that allows the dissociation between positive and negative feedback learning. We also fitted all participants' data to a Q-learning model and various actor-critic models that examine learning rate parameters from positive and negative feedback to investigate effects of valence vs. action on performance. SAD and GAD patients were more sensitive to negative feedback than either PAD patients or healthy participants. PAD, SAD, and GAD patients did not differ in positive-feedback learning compared to healthy participants. We found that Q-learning models provide the simplest fit of the data in comparison to other models. However, computational analysis revealed that groups did not differ in terms of learning rate or exploration values. These findings argue that (a) not all anxiety spectrum disorders share similar cognitive correlates, but are rather different in ways that do not link them to the hallmark of anxiety (higher sensitivity to negative feedback); and (b) perception of negative consequences is the core feature of GAD and SAD, but not PAD. Further research is needed to examine the similarities and differences between anxiety spectrum disorders in other cognitive domains and potential implementation of behavioral therapy to remediate cognitive deficits.

  19. The glucocorticoid/aggression relationship in animals and humans: an analysis sensitive to behavioral characteristics, glucocorticoid secretion patterns, and neural mechanisms.

    Science.gov (United States)

    Haller, József

    2014-01-01

    Glucocorticoids control a wide array of biological processes from glucose homeostasis to neuronal function. The mechanisms mediating their effects are similarly varied and include rapid and transient nongenomic effects on calcium trafficking, various neurotransmitter receptors, and other membrane/cytoplasmic proteins, as well as slowly developing but durable genomic effects that are mediated by a large number of glucocorticoid-sensitive genes that are affected after variable lag-times. Given this complexity, we suggest that the aggression/glucocorticoid relationship cannot be reduced to the simple "stimulation/inhibition" question. Here, we review the effects of glucocorticoids on aggression by taking into account the complexities of glucocorticoid actions. Acute and chronic effects were differentiated because these are mediated by different mechanisms. The effects of chronic increases and decreases in glucocorticoid production were discussed separately, because the activation of mechanisms that are not normally activated and the loss of normal functions should not be confounded. Findings in healthy/normal subjects and those obtained in subjects that show abnormal forms of behavior or psychopathologies were also differentiated, because the effects of glucocorticoids are indirect, and largely depend on the properties of neurons they act upon, which are altered in subjects with psychopathologies. In addition, the conditions of glucocorticoid measurements were also thoroughly evaluated. Although the role of glucocorticoids in aggression is perceived as controversial by many investigators, a detailed analysis that is sensitive to glucocorticoid and behavioral measure as well as to the mediating mechanism suggests that this role is rather clear-cut; moreover, there is a marked similarity between animal and human findings.

  20. Methylphenidate enhances the abuse-related behavioral effects of nicotine in rats: intravenous self-administration, drug discrimination, and locomotor cross-sensitization.

    Science.gov (United States)

    Wooters, Thomas E; Neugebauer, Nichole M; Rush, Craig R; Bardo, Michael T

    2008-04-01

    Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague-Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25-10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03-0.3 mg/kg) and methylphenidate (1.25-10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2-0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.

  1. Changes in sensitivity of reward and motor behavior to dopaminergic, glutamatergic, and cholinergic drugs in a mouse model of fragile X syndrome.

    Directory of Open Access Journals (Sweden)

    Eric W Fish

    Full Text Available Fragile X syndrome (FXS is a leading cause of intellectual disability. FXS is caused by loss of function of the FMR1 gene, and mice in which Fmr1 has been inactivated have been used extensively as a preclinical model for FXS. We investigated the behavioral pharmacology of drugs acting through dopaminergic, glutamatergic, and cholinergic systems in fragile X (Fmr1 (-/Y mice with intracranial self-stimulation (ICSS and locomotor activity measurements. We also measured brain expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in dopamine biosynthesis. Fmr1 (-/Y mice were more sensitive than wild type mice to the rewarding effects of cocaine, but less sensitive to its locomotor stimulating effects. Anhedonic but not motor depressant effects of the atypical neuroleptic, aripiprazole, were reduced in Fmr1 (-/Y mice. The mGluR5-selective antagonist, 6-methyl-2-(phenylethynylpyridine (MPEP, was more rewarding and the preferential M1 antagonist, trihexyphenidyl, was less rewarding in Fmr1 (-/Y than wild type mice. Motor stimulation by MPEP was unchanged, but stimulation by trihexyphenidyl was markedly increased, in Fmr1 (-/Y mice. Numbers of midbrain TH+ neurons in the ventral tegmental area were unchanged, but were lower in the substantia nigra of Fmr1 (-/Y mice, although no changes in TH levels were found in their forebrain targets. The data are discussed in the context of known changes in the synaptic physiology and pharmacology of limbic motor systems in the Fmr1 (-/Y mouse model. Preclinical findings suggest that drugs acting through multiple neurotransmitter systems may be necessary to fully address abnormal behaviors in individuals with FXS.

  2. Action-potential duration and the modulation of transmitter release from the sensory neurons of Aplysia in presynaptic facilitation and behavioral sensitization.

    Science.gov (United States)

    Hochner, B; Klein, M; Schacher, S; Kandel, E R

    1986-11-01

    Presynaptic facilitation of transmitter release from Aplysia sensory neurons is an important contributor to behavioral sensitization of the gill and siphon withdrawal reflex. The enhanced release is accompanied by reduction of the serotonin-sensitive S current in the sensory neurons and a consequent increase in duration of the presynaptic action potential (ranging from 10% to 30%). We find that changes of similar magnitude in the duration of depolarizing voltage-clamp steps in sensory neurons in intact abdominal ganglia yield increases in synaptic potentials of 45-120%. In dissociated cell culture, these changes lead to increases of 25-60% in the synaptic potential. Prolongation of presynaptic depolarization using voltage clamp or prolongation of the duration of the action potential by K(+)-channel blockers leads to prolongation of the time-to-peak of the synaptic potentials; similar changes in time-to-peak occur during presynaptic facilitation. The time-to-peak is not changed by homosynaptic depression or by changing the Ca(2+) concentration, procedures that alter release without changing the duration of the action potential. Preventing the spike from broadening by voltage clamping the presynaptic neuron substantially reduces or blocks the facilitation. These results suggest that broadening of the action potential during facilitation is a causal factor in the enhancement of transmitter release.

  3. Sensitive Period for the Recovery of the Response Rate of the Wind-Evoked Escape Behavior of Unilaterally Cercus-Ablated Crickets (Gryllus bimaculatus).

    Science.gov (United States)

    Takuwa, Hiroyuki; Kanou, Masamichi

    2015-04-01

    We examined the compensational recovery of the response rate (relative occurrence) of the wind-evoked escape behavior in unilaterally cercus-ablated crickets (Gryllus bimaculatus) and elucidated the existence of a sensitive period for such recovery by rearing the crickets under different conditions. In one experiment, each cricket was reared in an apparatus called a walking inducer (WI) to increase the sensory input to the remaining cercus, i.e., the self-generated wind caused by walking. In another experiment, each cricket was reared in a small plastic case separate from the outside atmosphere (wind-free: WF). In this rearing condition, the cricket did not experience self-generated wind as walking was prohibited. During the recovery period after the unilateral cercus ablation, the crickets were reared under either the WI or WF condition to investigate the role of the sensory inputs on the compensational recovery of the response rate. The compensational recovery of the response rate occurred only in the crickets reared under the WI condition during the early period after the ablation. In particular, WI rearing during the first three days after the ablation resulted in the largest compensational recovery in the response rate. In contrast, no compensational recovery was observed in the crickets reared under the WF condition during the first three days. These results suggest that a sensitive period exists in which sensory inputs from the remaining cercus affect the compensational recovery of the response rate more effectively than during other periods.

  4. Short-term food restriction followed by controlled refeeding promotes gorging behavior, enhances fat deposition, and diminishes insulin sensitivity in mice.

    Science.gov (United States)

    Kliewer, Kara L; Ke, Jia-Yu; Lee, Hui-Young; Stout, Michael B; Cole, Rachel M; Samuel, Varman T; Shulman, Gerald I; Belury, Martha A

    2015-07-01

    Rodents are commonly used in food restriction refeeding studies to investigate weight regain. Mice that are rationed food every 24 h may consume all allocated food in a short time (gorge) and therefore undergo a brief well-fed period followed by an extended fasted period until the next day's food allotment. These exaggerated metabolic states are not typical in mice fed ad libitum (nibbling). The aim of the current study was to elucidate the intraday and cumulative metabolic consequences of gorging (induced by food restriction) in mice during controlled refeeding. Accordingly, following a temporary food restriction, mice were fed rations similar to intakes of controls fed ad libitum. Temporary food restriction initiated gorging behavior that persisted during refeeding; consequently, metabolism-related measurements were obtained in the gorging mice during their daily fed and fasted metabolic states. Robust differences in adipose tissue lipogenic and inflammatory gene expression were found in the gorging mice by metabolic state (fed versus fasted). Additionally, despite a reduced cumulative food intake compared to mice fed ad libitum, restriction-induced gorging mice had increased intraabdominal fat accumulation, diminished hepatic and peripheral insulin sensitivity, and a gene expression profile favoring lipid deposition. Our findings highlight the intraday differences in gene expression in gorging mice before and after feeding that confound comparisons with mice fed ad libitum, or nibbling. The present study also provides evidence that weight regain following food restriction is associated with cumulative metabolic and behavioral abnormalities in mice.

  5. Developmental exposure to PBDE 99 and PCB affects estrogen sensitivity of target genes in rat brain regions and female sexual behavior

    Energy Technology Data Exchange (ETDEWEB)

    Lichtensteiger, W.; Faass, O.; Ceccatelli, R.; Schlumpf, M. [Zurich Univ. (Switzerland). Inst. of Pharmacology and Toxicology

    2004-09-15

    We recently reported effects of PBDE99 (2,2',4,4'5-pentabromoBDE) on sexual differentiation processes in rat reproductive organs and central nervous system. These studies were prompted by reports on an increase of PBDE levels in human milk, an indicator of the body burden of pregnant women and of potential exposure of the nursing infant, during the last decade. Even higher human adipose tissue and milk levels were reported for North America. PBDE99 is present in human and animal samples and exhibits developmental neurotoxicity in mice. The developing brain is subject to the organizing action of estradiol locally formed from circulating testosterone, and thus represents a target for endocrine active chemicals. One molecular mechanism by which chemicals may interfere with sexual brain differentiation, may be a change in the expression of sex hormone (estrogen)-regulated genes. Such effects may manifest themselves in mRNA expression levels, or in the sensitivity of the genes to estrogen. In order to detect alterations of the latter, more subtle parameter, we have conducted experiments in developmentally chemical-exposed rat offspring that were gonadectomized in adulthood and injected with a challenge dose of estradiol. Effects of PBDE99 were compared with those of a commercial PCB mixture, Aroclor 1254, which had previously been found to influence sexual brain differentiation. We analyzed the expression of estrogen-regulated genes in ventromedial hypothalamus (VMH) and medial preoptic area (MPO), two brain regions that are part of a network involved in the integration of environmental cues, sexual behavior and gonadal function. Since prominent changes were observed in VMH which is particularly important for female sexual behavior, the study was completed by a behavioral analysis.

  6. Neonatal co-lesion by DSP-4 and 5,7-DHT produces adulthood behavioral sensitization to dopamine D(2) receptor agonists.

    Science.gov (United States)

    Nowak, Przemysław; Nitka, Dariusz; Kwieciński, Adam; Jośko, Jadwiga; Drab, Jacek; Pojda-Wilczek, Dorota; Kasperski, Jacek; Kostrzewa, Richard M; Brus, Ryszard

    2009-01-01

    To assess the possible modulatory effects of noradrenergic and serotoninergic neurons on dopaminergic neuronal activity, the noradrenergic and serotoninergic neurotoxins DSP-4 N-(2-chlorethyl)-N-ethyl-2-bromobenzylamine (50.0 mg/kg, sc) and 5,7-dihydroxytryptamine (5,7-DHT) (37.5 microg icv, half in each lateral ventricle), respectively, were administered toWistar rats on the first and third days of postnatal ontogeny, and dopamine (DA) agonist-induced behaviors were assessed in adulthood. At eight weeks, using an HPLC/ED technique, DSP-4 treatment was associated with a reduction in NE content of the corpus striatum (> 60%), hippocampus (95%), and frontal cortex (> 85%), while 5,7-DHT was associated with an 80-90% serotonin reduction in the same brain regions. DA content was unaltered in the striatum and the cortex. In the group lesioned with both DSP-4 and 5,7-DHT, quinpirole-induced (DA D(2) agonist) yawning, 7-hydroxy-DPAT-induced (DA D(3) agonist) yawning, and apomorphine-induced (non-selective DA agonist) stereotypies were enhanced. However, SKF 38393-induced (DA D(1) agonist) oral activity was reduced in the DSP-4 + 5,7-DHT group. These findings demonstrate that DA D(2)- and D(3)-agonist-induced behaviors are enhanced while DA D(1)-agonist-induced behaviors are suppressed in adult rats in which brain noradrenergic and serotoninergic innervation of the brain has largely been destroyed. This study indicates that noradrenergic and serotoninergic neurons have a great impact on the development of DA receptor reactivity (sensitivity).

  7. Anxiety Sensitivity and Smoking Behavior Among Trauma-Exposed Daily Smokers: The Explanatory Role of Smoking-Related Avoidance and Inflexibility.

    Science.gov (United States)

    Bakhshaie, Jafar; Zvolensky, Michael J; Salazar, Adriana; Vujanovic, Anka A; Schmidt, Norman B

    2016-01-01

    Anxiety sensitivity (AS), defined as the extent to which individuals believe that anxiety-related sensations have harmful consequences, is associated with smoking processes and poorer clinical outcomes among trauma-exposed smokers. Yet the specific mechanisms underlying this association are unclear. Smoking-specific avoidance and inflexibility is a construct implicated in multiple manifestations of mood regulation that may underlie smoking behavior. The current study examined the explanatory role of smoking-specific avoidance and inflexibility in terms of the relation between AS and indices of smoking behavior among trauma-exposed smokers. The sample consisted of 217 treatment-seeking adult smokers (44% female; M age = 37.8; SD = 13.2; age range: 18-65 years), who were exposed to at least one lifetime Criterion A trauma event (Diagnostic and Statistical Manual of Mental Disorders [4th ed., text rev.; DSM-IV-TR] Criterion A for trauma exposure). Bootstrap analysis (5,000 re-samples) revealed that AS was indirectly related to the (a) number of cigarettes smoked per day, (b) number of years being a daily smoker, (c) number of failed quit attempts, and (d) heaviness of smoking index among trauma-exposed smokers through its relation with smoking-specific avoidance and inflexibility. These findings provide initial evidence suggesting that smoking-specific avoidance and inflexibility may be an important construct in better understanding AS-smoking relations among trauma-exposed smokers. Future work is needed to explore the extent to which smoking-specific avoidance and inflexibility account for relations between AS and other smoking processes (e.g., withdrawal, cessation outcome) in the context of trauma and smoking comorbidity.

  8. [The expression of AQP9 in HepG2 cells affects cell biological behaviors and sensitivity to As2O3].

    Science.gov (United States)

    Tang, Jie; Wang, Chuan; Jiang, Zheng

    2015-06-01

    To investigate the effect of aquaporin 9 (AQP9) expression level on the apoptosis and biological behaviors of HepG2 cells induced by arsenic trioxide (As2O3). The effects of different concentration As2O3 on the cell proliferation were measured by MTT assay, and IC50 was calculated. The recombinant plasmids pEGFP-N1-AQP9 and pshRNA-AQP9 were transfected into HepG2 cells. The expression of AQP9 mRNA and protein were detected by reverse transcription PCR and Western blotting, respectively. Then As2O3 was added to plasmid-transfected cells and untreated HepG2 cells. Cell proliferation was detected by MTT assay, cell cycle and apoptosis rate were determined by flow cytometry, and cell invasion and migration ability were examined by Transwell(TM) (Boyden Chamber) assay. The activity of caspase-3 was detected by microplate reader. The recombinant plasmids remarkably influenced the expression of AQP9. Compared with the group treated with As2O3 alone (control group), the cell proliferation, invasion and migration of HepG2 cells transfected with pEGFP-N1-AQP9 were attenuated significantly, while the cells transfected with pshRNA-AQP9 increased. The increasing population of apoptotic cells, augmented caspase 3 activity and highest percentage of cells stagnating at G0/G1 phase were observed in HepG2 cells transfected with pEGFP-N1-AQP9 as compared with the control HepG2 cells; in contrast, the HepG2 cells transfected with pshRNA-AQP9 presented with lower caspase 3 activity and stronger invasion and migration ability than the control HepG2 cells did. The alterations in the expression of AQP9 could affect the biological behaviors of HepG2 cells, but also their sensitivity to As2O3.

  9. Ozone production during the field campaign RISFEX 2003 in the Sea of Japan: analysis of sensitivity and behavior basing on an improved indicator

    Directory of Open Access Journals (Sweden)

    Z. Q. Wang

    2010-04-01

    Full Text Available An improved indicator Φ, based on the present indicator Θ=τOHVOCOHNOx, is developed to determine the sensitivity of ozone production to HC and NOx in the field campaign RISFEX 2003 (RIShiri Fall EXperiment 2003 made in September 2003 at Rishiri island (45.07° N, 141.12° E, and 35 m a.s.l. in the sea of Japan. The indicator, defined as a ratio of kHC+OH[HC] to kNOx+OH[NOx], has a close correlation with the relative sensitivity (dlnP(O3/dln[NO] and P(O3/dln[HC] which can explicitly give the sensitivity of P(O3 to NO and HC. According to the indicator, four distinctive regimes were obtained in which modeled P(O3 behaviors differently with HC and NOx. At Φ<1, P(O3 is located in Regime I and is greatly sensitive to both HC with a positive correlation and NOx with a negative one. In Regime II (1<Φ<7±3, P(O3 is more sensitive to HC than NOx, but has a similar relationship to HC and NOx. P(O3 is both positively sensitive to HC and NOx in Regime III (7±3<Φ<23±7. For a higher Φ in Regime IV, it was found that P(O3 is greatly sensitive to NOx but nearly insensitive to HC. During the campaign, 91% (247/271 of P(O3 data are located in Regime III and IV, illuminating that NOx is a limiting factor for ozone production. Hence a controlling of NOx emission can be a more efficient strategy for ozone abatement at the site.

    Detailed comparisons between the experimental and modeled P(O3 were performed in different regimes and the results show basically an agreement between the two methods. However, the model tended to underestimate

  10. Levamisole/Cocaine Induced Systemic Vasculitis and Immune Complex Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Lohit Garg

    2015-01-01

    Full Text Available Levamisole is an antihelminthic and immunomodulator medication that was banned by the USFDA in 1998. It has been increasingly used to adulterate cocaine due to its psychotropic effects and morphological properties. Adverse reactions including cutaneous vasculitis, thrombocytopenia, and agranulocytosis have been well described. Despite systemic vasculitis in this setting, renal involvement is uncommon. We report here a case of ANCA positive systemic vasculitis with biopsy proven immune complex mediated glomerulonephritis likely secondary to levamisole/cocaine. A 40-year-old Caucasian male with no past medical history presented with 3-week history of fatigue, skin rash, joint pains, painful oral lesions, oliguria, hematuria, worsening dyspnea on exertion, and progressive lower extremity edema. He had a history of regular tobacco and cocaine use. Lab testing revealed severe anemia, marked azotemia, deranged electrolytes, and 4.7 gm proteinuria. Rheumatologic testing revealed hypocomplementemia, borderline ANA, myeloperoxidase antibody, and positive atypical p-ANCA. Infectious and other autoimmune workup was negative. Kidney biopsy was consistent with immune mediated glomerulonephritis and showed mesangial proliferation and immune complex deposition consisting of IgG, IgM, and complement. High dose corticosteroids and discontinuing cocaine use resulted in marked improvement in rash, mucocutaneous lesions, and arthritis. There was no renal recovery and he remained hemodialysis dependent.

  11. Levamisole/Cocaine Induced Systemic Vasculitis and Immune Complex Glomerulonephritis.

    Science.gov (United States)

    Garg, Lohit; Gupta, Sagar; Swami, Abhishek; Zhang, Ping

    2015-01-01

    Levamisole is an antihelminthic and immunomodulator medication that was banned by the USFDA in 1998. It has been increasingly used to adulterate cocaine due to its psychotropic effects and morphological properties. Adverse reactions including cutaneous vasculitis, thrombocytopenia, and agranulocytosis have been well described. Despite systemic vasculitis in this setting, renal involvement is uncommon. We report here a case of ANCA positive systemic vasculitis with biopsy proven immune complex mediated glomerulonephritis likely secondary to levamisole/cocaine. A 40-year-old Caucasian male with no past medical history presented with 3-week history of fatigue, skin rash, joint pains, painful oral lesions, oliguria, hematuria, worsening dyspnea on exertion, and progressive lower extremity edema. He had a history of regular tobacco and cocaine use. Lab testing revealed severe anemia, marked azotemia, deranged electrolytes, and 4.7 gm proteinuria. Rheumatologic testing revealed hypocomplementemia, borderline ANA, myeloperoxidase antibody, and positive atypical p-ANCA. Infectious and other autoimmune workup was negative. Kidney biopsy was consistent with immune mediated glomerulonephritis and showed mesangial proliferation and immune complex deposition consisting of IgG, IgM, and complement. High dose corticosteroids and discontinuing cocaine use resulted in marked improvement in rash, mucocutaneous lesions, and arthritis. There was no renal recovery and he remained hemodialysis dependent.

  12. Cocaine-Induced Endocannabinoid Mobilization in the Ventral Tegmental Area.

    Science.gov (United States)

    Wang, Huikun; Treadway, Tyler; Covey, Daniel P; Cheer, Joseph F; Lupica, Carl R

    2015-09-29

    Cocaine is a highly addictive drug that acts upon the brain's reward circuitry via the inhibition of monoamine uptake. Endogenous cannabinoids (eCB) are lipid molecules released from midbrain dopamine (DA) neurons that modulate cocaine's effects through poorly understood mechanisms. We find that cocaine stimulates release of the eCB, 2-arachidonoylglycerol (2-AG), in the rat ventral midbrain to suppress GABAergic inhibition of DA neurons, through activation of presynaptic cannabinoid CB1 receptors. Cocaine mobilizes 2-AG via inhibition of norepinephrine uptake and promotion of a cooperative interaction between Gq/11-coupled type-1 metabotropic glutamate and α1-adrenergic receptors to stimulate internal calcium stores and activate phospholipase C. The disinhibition of DA neurons by cocaine-mobilized 2-AG is also functionally relevant because it augments DA release in the nucleus accumbens in vivo. Our results identify a mechanism through which the eCB system can regulate the rewarding and addictive properties of cocaine.

  13. Cocaine-Induced Endocannabinoid Mobilization in the Ventral Tegmental Area

    Directory of Open Access Journals (Sweden)

    Huikun Wang

    2015-09-01

    Full Text Available Cocaine is a highly addictive drug that acts upon the brain’s reward circuitry via the inhibition of monoamine uptake. Endogenous cannabinoids (eCB are lipid molecules released from midbrain dopamine (DA neurons that modulate cocaine’s effects through poorly understood mechanisms. We find that cocaine stimulates release of the eCB, 2-arachidonoylglycerol (2-AG, in the rat ventral midbrain to suppress GABAergic inhibition of DA neurons, through activation of presynaptic cannabinoid CB1 receptors. Cocaine mobilizes 2-AG via inhibition of norepinephrine uptake and promotion of a cooperative interaction between Gq/11-coupled type-1 metabotropic glutamate and α1-adrenergic receptors to stimulate internal calcium stores and activate phospholipase C. The disinhibition of DA neurons by cocaine-mobilized 2-AG is also functionally relevant because it augments DA release in the nucleus accumbens in vivo. Our results identify a mechanism through which the eCB system can regulate the rewarding and addictive properties of cocaine.

  14. Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening

    Energy Technology Data Exchange (ETDEWEB)

    Jiguet Jiglaire, Carine, E-mail: carine.jiguet-jiglaire@univ-amu.fr [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Baeza-Kallee, Nathalie; Denicolaï, Emilie; Barets, Doriane [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Metellus, Philippe [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); APHM, Timone Hospital, Department of Neurosurgery, 13005 Marseille (France); Timone Hospital, 264 Rue Saint Pierre, 13385 Marseille Cedex 5 (France); and others

    2014-02-15

    Identification of new drugs and predicting drug response are major challenges in oncology, especially for brain tumors, because total surgical resection is difficult and radiation therapy or chemotherapy is often ineffective. With the aim of developing a culture system close to in vivo conditions for testing new drugs, we characterized an ex vivo three-dimensional culture system based on a hyaluronic acid-rich hydrogel and compared it with classical two-dimensional culture conditions. U87-MG glioblastoma cells and seven primary cell cultures of human glioblastomas were subjected to radiation therapy and chemotherapy drugs. It appears that 3D hydrogel preserves the original cancer growth behavior and enables assessment of the sensitivity of malignant gliomas to radiation and drugs with regard to inter-tumoral heterogeneity of therapeutic response. It could be used for preclinical assessment of new therapies. - Highlights: • We have compared primary glioblastoma cell culture in a 2D versus 3D-matrix system. • In 3D morphology, organization and markers better recapitulate the original tumor. • 3D-matrix culture might represent a relevant system for more accurate drug screening.

  15. Preparation of pH-sensitive amphiphilic block star polymers, their self-assembling characteristics and release behavior on encapsulated molecules

    KAUST Repository

    Song, Xiaowan

    2016-05-28

    Poly(ethylene glycol) (PEG), a polymer with excellent biocompatibility, was widely used to form nanoparticles for drug delivery applications. In this paper, based on PEG, a series of pH-sensitive amphiphilic block star polymers of poly(ethylene glycol)-block-poly(ethoxy ethyl glycidyl ether) (PEG-b-PEEGE) with different hydrophobic length were synthesized by living anionic ring-opening polymerization method. The products were characterized using 1H NMR and gel permeation chromatography. These copolymers could self-assemble in aqueous solution to form micellar structure with controlled morphologies. Transmission electron microscopy showed that the nanoparticles are spherical or rodlike with different hydrophilic mass fractions. The pH response of polymeric aggregates from PEG-b-PEEGE was detected by fluorescence probe technique at different pH. A pH-dependent release behavior was observed and pH-responsiveness of PEG-b-PEEGE was affected by the hydrophobic block length. These results demonstrated that star-shaped polymers (PEG-b-PEEGE) are attractive candidates as anticancer drug delivery carriers. © 2016 Springer-Verlag Berlin Heidelberg

  16. Self-Reported Alcohol Consumption and Sexual Behavior in Males and Females: Using the Unmatched-Count Technique to Examine Reporting Practices of Socially Sensitive Subjects in a Sample of University Students

    Science.gov (United States)

    Walsh, Jeffrey A.; Braithwaite, Jeremy

    2008-01-01

    This work, drawing on the literature on alcohol consumption, sexual behavior, and researching sensitive topics, tests the efficacy of the unmatched-count technique (UCT) in establishing higher rates of truthful self-reporting when compared to traditional survey techniques. Traditional techniques grossly underestimate the scope of problems…

  17. Cross-sensitization between testosterone and cocaine in adolescent and adult rats.

    Science.gov (United States)

    Engi, Sheila A; Cruz, Fabio C; Crestani, Carlos C; Planeta, Cleopatra S

    2015-11-01

    Cocaine and anabolic-androgenic steroids are substances commonly co-abused. The use of anabolic steroids and cocaine has increased among adolescents. However, few studies investigated the consequences of the interaction between anabolic-androgenic steroids in animals' model of adolescence. We examined the effects of acute and repeated testosterone administration on cocaine-induced locomotor activity in adult and adolescent rats. Rats received ten once-daily subcutaneous (s.c.) injections of testosterone (10mg/kg) or vehicle. Three days after the last testosterone or vehicle injections rats received an intraperitoneal (i.p.) challenge injection of either saline or cocaine (10mg/kg). A different subset of rats was treated with a single injection of testosterone (10mg/kg) or vehicle and three days later was challenged with cocaine (10mg/kg, i.p.) or saline. Immediately after cocaine or saline injections the locomotor activity was recorded during forty minutes. Our results demonstrated that repeated testosterone induced locomotor sensitization to cocaine in adolescent but not adult rats.

  18. The effects of cannabinoid CB1, CB2 and vanilloid TRPV1 receptor antagonists on cocaine addictive behavior in rats.

    Science.gov (United States)

    Adamczyk, Przemysław; Miszkiel, Joanna; McCreary, Andrew C; Filip, Małgorzata; Papp, Mariusz; Przegaliński, Edmund

    2012-03-20

    There is evidence that indicates that tonic activation of cannabinoid CB1 receptors plays a role in extinction/reinstatement of cocaine seeking-behavior but is not involved in the maintenance of cocaine self-administration. To further explore the importance of other endocannabinoid-related receptors in an animal model of cocaine addiction, the present paper examines cannabinoid CB2 receptor antagonist N-((1S)-endo-1,3,3-trimethylbicyclo(2.2.1)heptan-2-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) and the transient receptor potential vanilloid type-1 (TRPV1) receptor antagonist N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791) on intravenous (i.v.) cocaine self-administration and extinction/reinstatement of cocaine-seeking behavior in rats. For comparison and reference purposes, the effect of the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) was also examined. Moreover, for comparison effects of those drugs on operant lever responding for artificial (cocaine) vs. natural (food) reward, food self-administration was also evaluated. Our findings show that AM251 (1-3mg/kg), SR144528 (0.1-1mg/kg) and SB366791 (0.3-1mg/kg) did not affect cocaine self-administration. However, AM251 (0.1-1mg/kg), SR144528 (0.1-1mg/kg) and SB366791 (0.1-1mg/kg) decreased cocaine-induced reinstatement of cocaine-seeking behavior, and AM251 (0.3-1mg/kg) decreased cue-induced reinstatement. Moreover, AM251 (3mg/kg), SR144528 (0.1-1mg/kg) and SB366791 (0.1-1mg/kg) slightly decreased food self-administration behavior, but only AM251 (3mg/kg) reduced food reward. In conclusion, our results indicate for the first time, that tonic activation of CB2 or TRPV1 receptors is involved in cocaine-induced reinstatement of cocaine-seeking behavior, but their activity is not necessary for the rewarding effect of this psychostimulant. In contrast to CB1 receptors, neither CB2 nor

  19. Co-sensitivity to the incentive properties of palatable food and cocaine in rats; implications for co-morbid addictions.

    Science.gov (United States)

    Levy, AnneMarie; Salamon, Avi; Tucci, Mark; Limebeer, Cheryl L; Parker, Linda A; Leri, Francesco

    2013-09-01

    Several lines of evidence suggest that there may be a shared vulnerability to acquire behaviors motivated by strong incentive stimuli. Non-food restricted male Sprague-Dawley rats (n = 78) underwent place conditioning with Oreos, and were subsequently tested on cocaine self-administration (SA) on fixed and progressive ratios, as well as extinction and reinstatement by cocaine primes and by consumption of Oreos. Although there was a group preference for the Oreo-paired compartment, at the individual level some rats (69%) displayed a preference and others did not. In cocaine SA, 'preference' rats achieved higher break points on a progressive ratio, and displayed greater responding during extinction and cocaine-induced reinstatement. Within the context of this study, Oreo-cocaine cross-reinstatement was not observed. In a control study, rats (n = 29) conditioned with a less palatable food (rice cakes) also displayed individual differences in place preference, but not on subsequent cocaine tests. These findings indicate that there is a relationship between incentive learning promoted by palatable foods and by cocaine. This supports the hypothesis that co-morbid food-drug addictions may result from a shared vulnerability to acquire behaviors motivated by strong incentives.

  20. Cellular and behavioral outcomes of dorsal striatonigral neuron ablation: new insights into striatal functions.

    Science.gov (United States)

    Révy, Delphine; Jaouen, Florence; Salin, Pascal; Melon, Christophe; Chabbert, Dorian; Tafi, Elisiana; Concetta, Lena; Langa, Francina; Amalric, Marianne; Kerkerian-Le Goff, Lydia; Marie, Hélène; Beurrier, Corinne

    2014-10-01

    The striatum is the input structure of the basal ganglia network that contains heterogeneous neuronal populations, including two populations of projecting neurons called the medium spiny neurons (MSNs), and different types of interneurons. We developed a transgenic mouse model enabling inducible ablation of the striatonigral MSNs constituting the direct pathway by expressing the human diphtheria toxin (DT) receptor under the control of the Slc35d3 gene promoter, a gene enriched in striatonigral MSNs. DT injection into the striatum triggered selective elimination of the majority of striatonigral MSNs. DT-mediated ablation of striatonigral MSNs caused selective loss of cholinergic interneurons in the dorsal striatum but not in the ventral striatum (nucleus accumbens), suggesting a region-specific critical role of the direct pathway in striatal cholinergic neuron homeostasis. Mice with DT injection into the dorsal striatum showed altered basal and cocaine-induced locomotion and dramatic reduction of L-DOPA-induced dyskinesia in the parkinsonian condition. In addition, these mice exhibited reduced anxiety, revealing a role of the dorsal striatum in the modulation of behaviors involving an emotional component, behaviors generally associated with limbic structures. Altogether, these results highlight the implication of the direct striatonigral pathway in the regulation of heterogeneous functions from cell survival to regulation of motor and emotion-associated behaviors.

  1. Cognitive and Emotion-Regulatory Mediators of the Relationship between Behavioral Approach System Sensitivity and Non-Suicidal Self-Injury Frequency

    OpenAIRE

    Burke, Taylor A.; Stange, Jonathan P.; Hamilton, Jessica L.; Cohen, Jonah N.; O’Garro-Moore, Jared; Daryanani, Issar; Abramson, Lyn Y.; Alloy, Lauren B.

    2014-01-01

    Non-suicidal self-injury (NSSI) is highly prevalent among late adolescents and predicts the onset of suicidal ideation and behavior. Although research has established an association between the behavioral approach system (BAS) and NSSI, less research has explored mechanisms underlying this relationship. The authors examined negative and positive emotion regulation patterns, as well as the BAS-relevant cognitive style of self-criticism, as potential mechanisms through which a hypersensitive BA...

  2. The Combination of Marketed Antagonists of α1b-Adrenergic and 5-HT2A Receptors Inhibits Behavioral Sensitization and Preference to Alcohol in Mice: A Promising Approach for the Treatment of Alcohol Dependence.

    Directory of Open Access Journals (Sweden)

    Fabrice Trovero

    Full Text Available Alcohol-dependence is a chronic disease with a dramatic and expensive social impact. Previous studies have indicated that the blockade of two monoaminergic receptors, α1b-adrenergic and 5-HT2A, could inhibit the development of behavioral sensitization to drugs of abuse, a hallmark of drug-seeking and drug-taking behaviors in rodents. Here, in order to develop a potential therapeutic treatment of alcohol dependence in humans, we have blocked these two monoaminergic receptors by a combination of antagonists already approved by Health Agencies. We show that the association of ifenprodil (1 mg/kg and cyproheptadine (1 mg/kg (α1-adrenergic and 5-HT2 receptor antagonists marketed as Vadilex ® and Periactine ® in France, respectively blocks behavioral sensitization to amphetamine in C57Bl6 mice and to alcohol in DBA2 mice. Moreover, this combination of antagonists inhibits alcohol intake in mice habituated to alcohol (10% v/v and reverses their alcohol preference. Finally, in order to verify that the effect of ifenprodil was not due to its anti-NMDA receptors property, we have shown that a combination of prazosin (0.5 mg/kg, an α1b-adrenergic antagonist, Mini-Press ® in France and cyproheptadine (1 mg/kg could also reverse alcohol preference. Altogether these findings strongly suggest that combined prazosin and cyproheptadine could be efficient as a therapy to treat alcoholism in humans. Finally, because α1b-adrenergic and 5-HT2A receptors blockade also inhibits behavioral sensitization to psychostimulants, opioids and tobacco, it cannot be excluded that this combination will exhibit some efficacy in the treatment of addiction to other abused drugs.

  3. The dual temperature/pH-sensitive multiphase behavior of poly(N-isopropylacrylamide-co-acrylic acid) microgels for potential application in in situ gelling system.

    Science.gov (United States)

    Xiong, Wei; Gao, Xiang; Zhao, Yanbing; Xu, Huibi; Yang, Xiangliang

    2011-05-01

    Poly(N-isopropylacrylamide-co-acrylic acid) microgels (PNA) may be an excellent formulation for in situ gelling system due to their high sensitivity and fast response rate. Four monodispersed PNA microgels with various contents of acrylic acid (AA) were synthesized by emulsion polymerization in this paper. Their hydrodynamic diameters decreased reversibly with both decreasing pH and increasing temperature. The dual temperature/pH-sensitivity was influenced by many factors such as AA content, cross-link density and ion strength. In addition, high concentration PNA dispersions underwent multiple phase transition according to different temperatures, pHs and concentrations, which were summarized in a 3D sol-gel phase diagram in this study. According to the sol-gel phase transition, 8% PNA-025 dispersion maintained a relatively low viscosity and favorable fluidity at pH 5.0 in the temperature range of 25-40°C, but it rapidly increased in viscosity at pH 7.4 and gelled at 37°C. This feature enabled the dual temperature/pH-sensitive microgels to overcome the troubles in syringing of temperature sensitive materials during the injection. Apart from this, PNA could form gel well in in vitro (e.g., medium and serum) and in in vivo with low cytotoxicity. Therefore, it is promising for PNA to be applied in the in situ gelling system.

  4. The Different Sensitive Behaviors of a Hydrogen-Bond Acidic Polymer-Coated SAW Sensor for Chemical Warfare Agents and Their Simulants

    Directory of Open Access Journals (Sweden)

    Yin Long

    2015-07-01

    Full Text Available A linear hydrogen-bond acidic (HBA linear functionalized polymer (PLF, was deposited onto a bare surface acoustic wave (SAW device to fabricate a chemical sensor. Real-time responses of the sensor to a series of compounds including sarin (GB, dimethyl methylphosphonate (DMMP, mustard gas (HD, chloroethyl ethyl sulphide (2-CEES, 1,5-dichloropentane (DCP and some organic solvents were studied. The results show that the sensor is highly sensitive to GB and DMMP, and has low sensitivity to HD and DCP, as expected. However, the sensor possesses an unexpected high sensitivity toward 2-CEES. This good sensing performance can’t be solely or mainly attributed to the dipole-dipole interaction since the sensor is not sensitive to some high polarity solvents. We believe the lone pair electrons around the sulphur atom of 2-CEES provide an electron-rich site, which facilitates the formation of hydrogen bonding between PLF and 2-CEES. On the contrary, the electron cloud on the sulphur atom of the HD molecule is offset or depleted by its two neighbouring strong electron-withdrawing groups, hence, hydrogen bonding can hardly be formed.

  5. The Different Sensitive Behaviors of a Hydrogen-Bond Acidic Polymer-Coated SAW Sensor for Chemical Warfare Agents and Their Simulants.

    Science.gov (United States)

    Long, Yin; Wang, Yang; Du, Xiaosong; Cheng, Luhua; Wu, Penglin; Jiang, Yadong

    2015-07-28

    A linear hydrogen-bond acidic (HBA) linear functionalized polymer (PLF), was deposited onto a bare surface acoustic wave (SAW) device to fabricate a chemical sensor. Real-time responses of the sensor to a series of compounds including sarin (GB), dimethyl methylphosphonate (DMMP), mustard gas (HD), chloroethyl ethyl sulphide (2-CEES), 1,5-dichloropentane (DCP) and some organic solvents were studied. The results show that the sensor is highly sensitive to GB and DMMP, and has low sensitivity to HD and DCP, as expected. However, the sensor possesses an unexpected high sensitivity toward 2-CEES. This good sensing performance can't be solely or mainly attributed to the dipole-dipole interaction since the sensor is not sensitive to some high polarity solvents. We believe the lone pair electrons around the sulphur atom of 2-CEES provide an electron-rich site, which facilitates the formation of hydrogen bonding between PLF and 2-CEES. On the contrary, the electron cloud on the sulphur atom of the HD molecule is offset or depleted by its two neighbouring strong electron-withdrawing groups, hence, hydrogen bonding can hardly be formed.

  6. The neuroinflammatory and behavioral response to recurrent psychosocial stress: An [11C]PBR28 PET imaging study in stress-sensitized aged rats

    NARCIS (Netherlands)

    Kopschina Feltes, Paula; de Vries, Erik; Juárez Orozco, Luis; Vállez García, David; Moriguchi Jeckel, Cristina; Dierckx, Rudi; Doorduin, Janine

    2016-01-01

    Introduction: Neuroinflammation plays an important role in the relationship between psychosocial stress and depressive-like behavior. However, it is still unknown if prior exposure to psychosocial stress has long-term influences in the response to a recurrence of the stressful stimulus later in life

  7. Sensitivity analysis

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003741.htm Sensitivity analysis To use the sharing features on this page, please enable JavaScript. Sensitivity analysis determines the effectiveness of antibiotics against microorganisms (germs) ...

  8. Emotion and cognition in high and low stress sensitive mouse strains: a combined neuroendocrine and behavioral study in BALB/c and C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    Vera Brinks

    2007-12-01

    Full Text Available Emotionally arousing experiences and stress influence cognitive processes and vice versa. Understanding the relations and interactions between these three systems forms the core of this study. We tested two inbred mouse strains (BALB/c, C57BL/6J; male; 3-month-old for glucocorticoid stress system markers (expression of MR and GR mRNA and protein in hippocampus, amygdala, and prefrontal cortex; blood plasma corticosterone, used behavioral tasks for emotions and cognitive performance (elevated plus maze, holeboard to assess the interdependence of these factors. We hypothesize that BALB/c mice have a stress-vulnerable neuroendocrine phenotype and that emotional expressions in BALB/c and C57BL/6J mice will differentially contribute to learning and memory. We applied factor analyses on emotional and cognitive parameters to determine the behavioral structure of BALB/c and C57BL/6J mice. Glucocorticoid stress system markers indeed show that BALB/c mice are more stress-vulnerable than C57BL/6J mice. Moreover, emotional and explorative factors differed between naïve BALB/c and C57BL/6J mice. BALB/c mice display high movement in anxiogenic zones and high risk assessment, while C57BL/6J mice show little movement in anxiogenic zones and display high vertical exploration. Furthermore, BALB/c mice are superior learners, showing learning related behavior which is highly structured and emotionally biased when exposed to a novel or changing situation. In contrast, C57BL/6J mice display a rather ‘‘chaotic’’ behavioral structure during learning in absence of an emotional factor. These results show that stress vulnerability coincides with more emotionality, which drives well orchestrated goal directed behavior to the benefit of cognition. Both phenotypes have their advantage depending on environmental demands.

  9. METHYLPHENIDATE ENHANCES THE ABUSE-RELATED BEHAVIORAL EFFECTS OF NICOTINE IN RATS: INTRAVENOUS SELF-ADMINISTRATION, DRUG DISCRIMINATION AND LOCOMOTOR CROSS-SENSITIZATION

    OpenAIRE

    Wooters, Thomas E.; Neugebauer, Nichole M.; Rush, Craig R.; Bardo, Michael T.

    2007-01-01

    Stimulant drugs, including d-amphetamine, cocaine and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination and locomotor cross-se...

  10. Sensitivity of Complex Networks

    CERN Document Server

    Angulo, Marco Tulio; Liu, Yang-Yu; Barabási, Albert-László

    2016-01-01

    The sensitivity (i.e. dynamic response) of complex networked systems has not been well understood, making difficult to predict whether new macroscopic dynamic behavior will emerge even if we know exactly how individual nodes behave and how they are coupled. Here we build a framework to quantify the sensitivity of complex networked system of coupled dynamic units. We characterize necessary and sufficient conditions for the emergence of new macroscopic dynamic behavior in the thermodynamic limit. We prove that these conditions are satisfied only for architectures with power-law degree distributions. Surprisingly, we find that highly connected nodes (i.e. hubs) only dominate the sensitivity of the network up to certain critical frequency.

  11. 眼镜蛇毒粗毒毒素Ⅳ对小鼠吗啡行为敏化的影响%The effects of cobravenom cytotoxin IV on morphine-induced behavioral sensitization in mice

    Institute of Scientific and Technical Information of China (English)

    仲维高; 崔跃; 孔天翰

    2012-01-01

    Objective To investigate the effects of cobravenom cytotoxin IV on morphine-induced sensitization in mice. Methods Locomotor activity was measured every 5 minutes for 1 hour immediately after administration with cobravenom cytotoxin IV in mice. The morphine-induced sensitization models were established in mice by subcutaneous injection with morphine 10mg/kg,once a day,for 7 days,and the mice were treated with the combination of morphine ( sc) with cytotoxin IV ( ip) to observe the effects of cytotoxin IV on the behavioral sensitization to morphine in mice. Results After treated with different doses of cytotoxin IV ( 0. 027,0. 04, 0. 08mg/kg,respectively), the locomotor activity of the mice was reduced, hyperactivity was inhibited, and the expression of morphine-induced behavioral sensitization was blocked, in which the effects of middle and high-dose of cytotoxin IV were more significant. Conclusion The cobravenom cytotoxin IV has inhibitory effects on central nervous system and can prohibit the formation of morphine addictive behavior, which suggests that cobravenom cytotoxin IV may have intervention effect on psychological dependence to morphine.%目的 探讨眼镜蛇毒毒素Ⅳ对吗啡行为敏化的影响.方法 测定小鼠自主活动,观察毒素Ⅳ对小鼠自主活动影响.昆明种小鼠慢性吗啡处理,建立吗啡诱导行为敏化模型,观察毒素Ⅳ对吗啡行为敏化影响.结果 毒素Ⅳ(0.027、0.04、0.08 mg/kg)腹腔注射后,均能减少小鼠自主活动,降低吗啡诱导的高活动性,抑制小鼠吗啡行为敏化的获得,阻断小鼠吗啡行为敏化表达,其中中、高剂量毒素Ⅳ作用较显著.结论 毒素Ⅳ对中枢神经系统具有抑制作用,可以阻止吗啡成瘾行为形成,对吗啡诱导的敏化行为具有抑制作用,提示毒素Ⅳ对吗啡精神依赖性可能具有干预作用.

  12. Cognitive and Emotion-Regulatory Mediators of the Relationship between Behavioral Approach System Sensitivity and Non-Suicidal Self-Injury Frequency

    Science.gov (United States)

    Burke, Taylor A.; Stange, Jonathan P.; Hamilton, Jessica L.; Cohen, Jonah N.; O’Garro-Moore, Jared; Daryanani, Issar; Abramson, Lyn Y.; Alloy, Lauren B.

    2014-01-01

    Non-suicidal self-injury (NSSI) is highly prevalent among late adolescents and predicts the onset of suicidal ideation and behavior. Although research has established an association between the behavioral approach system (BAS) and NSSI, less research has explored mechanisms underlying this relationship. The authors examined negative and positive emotion regulation patterns, as well as the BAS-relevant cognitive style of self-criticism, as potential mechanisms through which a hypersensitive BAS might be related to NSSI frequency. Late adolescents (N=177) with high and moderate BAS levels completed measures of self-criticism, positive emotion regulation, brooding, and both lifetime and last year frequency of NSSI. Results indicated that self-criticism and positive emotion dampening independently mediated the relationship between BAS and last year frequency of NSSI. Self-criticism also mediated the relationship between BAS and lifetime frequency of NSSI. Results suggest that cognitive and emotion-regulatory styles may help to explain why high BAS individuals are likely to engage in NSSI. PMID:25443691

  13. Health information, behavior change, and decision support for patients with type 2 diabetes: development of a tailored, preference-sensitive health communication application

    Directory of Open Access Journals (Sweden)

    Weymann N

    2013-10-01

    Full Text Available Nina Weymann,1 Martin Härter,1 Frank Petrak,2 Jörg Dirmaier11Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, 2Clinic of Psychosomatic Medicine and Psychotherapy, LWL University Hospital, Ruhr-University Bochum, Bochum, GermanyPurpose: Patient involvement in diabetes treatment such as shared decision-making and patient self-management has significant effects on clinical parameters. As a prerequisite for active involvement, patients need to be informed in an adequate and preference-sensitive way. Interactive Health Communication Applications (IHCAs that combine web-based health information for patients with additional support offer the opportunity to reach great numbers of patients at low cost and provide them with high-quality information and support at the time, place, and learning speed they prefer. Still, web-based interventions often suffer from high attrition. Tailoring the intervention to patients’ needs and preferences might reduce attrition and should thereby increase effectiveness. The purpose of this study was to develop a tailored IHCA offering evidence-based, preference-sensitive content and treatment decision support to patients with type 2 diabetes. The content was developed based on a needs assessment and two evidence-based treatment guidelines. The delivery format is a dialogue-based, tunneled design tailoring the content and tone of the dialogue to relevant patient characteristics (health literacy, attitudes toward self-care, and psychological barriers to insulin treatment. Both content and tailoring were revised by an interdisciplinary advisory committee.Conclusion: The World Wide Web holds great potential for patient information and self-management interventions. With the development and evaluation of a tailored IHCA, we complement face-to-face consultations of patients with their health care practitioners and make them more efficient and satisfying for both sides. Effects of the

  14. Phosphorescence behavior and photoluminescence mechanism of Dy{sup 3+} sensitized β-Zn{sub 3}(PO{sub 4}){sub 2}: Mn{sup 2+} phosphor

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Ting; Guo, Hongxu [School of Chemistry & Environment, Minnan Normal University, Zhangzhou 363000, Fujian (China); Zhang, Junying [Department of Physics, Beihang University, Beijing 100191 (China); Odetola, Christopher [Department of Chemistry, University of Ontario Institute of Technology, Ontario L1H 7K4 (Canada); He, Yuneng; Lin, Heng; Chen, Guoliang [School of Chemistry & Environment, Minnan Normal University, Zhangzhou 363000, Fujian (China); Zheng, Zishan, E-mail: Z.Zheng@mnnu.edu.cn [School of Chemistry & Environment, Minnan Normal University, Zhangzhou 363000, Fujian (China)

    2015-09-05

    Highlights: • A red long persistent phosphor of β-Zn{sub 3}(PO{sub 4}){sub 2}: Mn{sup 2+}, Dy{sup 3+} was synthesized. • Dy{sup 3+} as a sensitizer transfers its energy to the luminescent center of Mn{sup 2+}. • The three factors are responsible for the improvement of LPP properties. - Abstract: A red long persistent phosphor (LPP) of β-Zn{sub 3}(PO{sub 4}){sub 2}: Mn{sup 2+}, Dy{sup 3+} was synthesized conventionally via homogeneous coprecipitation and conventional solid-state sintering methods. The emission peak of phosphor was found at 620 nm, which can be assigned to the {sup 4}T{sub 1g} → {sup 6}A{sub 1g} transition of Mn{sup 2+}. The decay curves of phosphors show that Dy{sup 3+} ions co-doping can largely improve the performance of the red LLP of β-Zn{sub 3}(PO{sub 4}){sub 2}: Mn{sup 2+}. This red long-persistent luminescence was observed for about 4 h in the limit of light perception for naked eyes when excited under 254 nm UV light for 5 min. Thermoluminescence analysis indicates that the dopant of Dy{sup 3+} ions produced suitable trap depth of defects that enhanced the luminescence of LPP. It is hypothesized that Dy{sup 3+} as a sensitizer transfers its energy to the luminescent center of Mn{sup 2+}. We propose that the emission mechanism of LPP experiences a series process of electron–hole pairs: production, release, movement and combination. The decay time of LPP has close relationship with the life span of electron–hole pairs during their releasing time from traps and moving length on their path.

  15. Preparation, characterization, and in vitro drug release behavior of glutathione-sensitive long-circulation micelles based on polyethylene glycol prodrug.

    Science.gov (United States)

    Shi, Liyan; Ding, Kaikai; Sun, Xin; Zhang, Ling; Zeng, Tian; Yin, Yihua; Zheng, Hua

    2016-01-01

    In this paper, a kind of glutathione-sensitive polymeric micelles was prepared through assembling in aqueous solution of an amphiphilic polymeric prodrug which was synthesized by linkage of 6-mercaptopurine (6-MP) and polyethylene glycol monomethyl ether using propiolic acid as a connecting arm. The glutathione (GSH)-sensitive strategy is based on a Michael addition-elimination reaction, that is the amphiphilic polymeric prodrug which contains α, β-unsaturated carbonyl group acts as a Michael acceptor to receive the attack of nucleophile - glutathione, and undergoes elimination reaction to release the original drug. Transmission electron microscope observation showed that the polymeric micelles (PMs) had a spherical-like morphology with a mean diameter of 28 ± 3.2 nm. The dynamic light scattering investigation data exhibited that the size and distribution changes of PMs are negligible after being placed for 15 days. In vitro drug release study indicated that only less than 13% of 6-MP was released from the micelles under GSH stimulation at micromolar level, while 34.5, 53.7, and 77.8% accumulative release rates were achieved under GSH stimulation at millimolar level (1, 2 and 10 mM), respectively. The cell inhibition rate of PM solution against HL-60 cells carried out by MTT method reached 85%. The cellular uptake and the intracellular drug release of PMs in HL-60 cells were observed through determining the intracellular 6-MP content by UV-vis spectrophotometer. In vitro macrophage uptake study showed a low phagocytosis rate, indicating the long-circulation ability of the PMs.

  16. An APP Sensitive Behaviors Detection Method Based on Android Kernel and Its Implementation%一种基于Android内核的APP敏感行为检测方法及实现

    Institute of Scientific and Technical Information of China (English)

    文伟平; 汤炀; 谌力

    2016-01-01

    进入移动智能终端时代后,Android手机操作系统由于其开放、免费的特点,成为市场上的主流操作系统之一。然而,大量针对Android系统编写的病毒、木马和恶意软件已经严重威胁到智能手机用户的个人隐私和财产安全。虽然在Android系统中进行敏感操作必须向系统申请相应的权限,Android系统中也存在权限控制相关的系统模块,但是恶意软件可以借助系统漏洞或第三方程序漏洞进行攻击。鉴于Android应用敏感行为检测的需要,文章研究分析了现有Android系统中应用程序行为检测方法,设计并实现了针对Android系统应用程序的动态行为监测系统,该系统能够实时监控应用程序的敏感行为,为恶意程序检测提供帮助。%In the era of intelligent mobile terminal, because of the characteristics of openness and free of charge, Android has become one of the major operation systems on the market. However, a large number of Android viruses, Trojans and malicious software have been serious threats to the privacy and property securities of smart phone users. In the Android operation system, although it is necessary to apply the authorities to the system for sensitive operations, and there are some system modules related to authority control, malicious software can use the system vulnerabilities or third party program vulnerabilities to carry out the attack. To meet the need of Android applications sensitive behaviors detection, this paper analyzes the popular applications behaviors detection tools in the Android system, designs and implements an Android applications dynamic detection system. The system can monitor the Android applications sensitive behaviors in real time, and provides help for the detection of malicious programs.

  17. Climate Sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Lindzen, Richard [M.I.T.

    2011-11-09

    Warming observed thus far is entirely consistent with low climate sensitivity. However, the result is ambiguous because the sources of climate change are numerous and poorly specified. Model predictions of substantial warming aredependent on positive feedbacks associated with upper level water vapor and clouds, but models are notably inadequate in dealing with clouds and the impacts of clouds and water vapor are intimately intertwined. Various approaches to measuring sensitivity based on the physics of the feedbacks will be described. The results thus far point to negative feedbacks. Problems with these approaches as well as problems with the concept of climate sensitivity will be described.

  18. Gluten Sensitivity

    Science.gov (United States)

    Gluten is a protein found in wheat, rye, and barley. It is found mainly in foods but ... products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different ...

  19. Sensitivity study for accident tolerant fuels: Property comparisons and behavior simulations in a simplified PWR to enable ATF development and design

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, Kristina Yancey, E-mail: kristina.yancey@gmail.com; Sudderth, Laura; Brito, Ryan A.; Evans, Jordan A.; Hart, Clifford S.; Hu, Anbang; Jati, Andi; Stern, Karyn; McDeavitt, Sean M., E-mail: mcdeavitt@tamu.edu

    2016-12-01

    Highlights: • This study compared four accident tolerant fuels against uranium dioxide. • Material property correlations were developed to evaluate fuel performance. • The fuels’ neutronic and thermal hydraulic behaviors were studied in the AP1000. • No fuel type performed better in all areas, but each has strengths and weaknesses. • More research is needed to build a complete model of the fuel performances. - Abstract: Since the events at the Fukushima-Daiichi nuclear power plant, there has been increased interest in developing fuels to better withstand accidents for current light water reactors. Four accident tolerant fuel candidates are uranium oxide with beryllium oxide additives, uranium oxide with silicon carbide matrix additives, uranium nitride, and uranium nitride with uranium silicide composite. The first two candidates represent near-term high performance uranium oxide with high thermal conductivity and neutron transparency, and the second two represent mid-term high-density fuels with highly beneficial thermal properties. This study seeks to understand the benefits and drawbacks of each option in place of uranium dioxide. To assess the material properties for each of the fuel types, an extensive literature review was performed for material property data. Correlations were then made to evaluate the properties during reactor operation. Neutronics and thermal hydraulics studies were also completed to determine the impact of the use of each candidate in an AP1000 reactor. In most cases, the candidate fuels performed more desirably than uranium dioxide, but no fuel type performed better in all aspects. Much more research needs to be performed to build a complete model of the fuel performances, primarily experimental data for uranium silicide. Each of the fuels studied has its own benefits and drawbacks, and the comparisons discussed in this report can be used to aid in determining the most appropriate fuel depending on the desired specifications.

  20. Dull to Social Acceptance Rather than Sensitivity to Social Ostracism in Interpersonal Interaction for Depression: Behavioral and Electrophysiological Evidence from Cyberball Tasks

    Science.gov (United States)

    Zhang, Qing; Li, Xiaosi; Wang, Kai; Zhou, Xiaoqin; Dong, Yi; Zhang, Lei; Xie, Wen; Mu, Jingjing; Li, Hongchen; Zhu, Chunyan; Yu, Fengqiong

    2017-01-01

    3 amplitudes were borderline negatively correlated with their scores of anhedonia symptoms. Limitations: A limitation of our study was that the subjects' criteria were different. Conclusions: The behavioral and electrophysiological results indicated that the interpersonal problems in depressive patients were mainly due to deficits in processing the pleasurable social stimuli rather than aversive social cues.

  1. Dopamine D3 and D2 receptor mechanisms in the abuse-related behavioral effects of cocaine: studies with preferential antagonists in squirrel monkeys.

    Science.gov (United States)

    Achat-Mendes, Cindy; Grundt, Peter; Cao, Jianjing; Platt, Donna M; Newman, Amy Hauck; Spealman, Roger D

    2010-08-01

    Dopamine (DA) D3 and D2 receptor mechanisms are implicated in cocaine's abuse-related behavioral effects, but the relative contribution of the two receptor subtypes is only partially characterized. This study investigated the role of D3 and D2 subtype mechanisms by determining the degree to which the D3-preferring antagonist PG01037 [N-{4-[4-(2,3-dichlorophenyl)-piperazin- 1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide HCl] and the D2-preferring antagonist L-741626 [3-[4-(4-chlorophenyl)-4- hydroxypiperidin-1-yl]methyl-1H-indole] attenuated several behavioral effects of cocaine in squirrel monkeys. Quantitative observational studies established doses of each antagonist that did not produce untoward effects, which were used in subsequent comparisons. In addition, the ability of the D3-preferring agonist PD128907 [(R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol)] and the D2-preferring agonist sumanirole [(R)-5,6-dihydro-5-(methylamino)-4H- imidazo[4,5,1-ij]quinolin-2(1H)-one(Z)-2-butenedioate] to reproduce cocaine's discriminative stimulus (DS) and priming effects were compared. In monkeys trained to discriminate cocaine from vehicle, both DA antagonists attenuated and both DA agonists partially reproduced cocaine's DS effects. PG01037 also selectively attenuated the cocaine-like DS effects of PD128907, whereas L-741626 attenuated the cocaine-like DS effects of both agonists. In self-administration studies, L-741626 nonselectively reduced cocaine- and food-maintained responding, whereas PG01037 was ineffective against either reinforcer. In studies involving reinstatement of extinguished cocaine seeking, both antagonists attenuated cocaine-induced reinstatement of responding, and both agonists induced at least partial reinstatement of cocaine seeking. L-741626 also attenuated sumanirole-induced, but not PD128907-induced, reinstatement of responding, whereas PG01037 was ineffective against either DA agonist. The results are

  2. Risk-sensitive reinforcement learning.

    Science.gov (United States)

    Shen, Yun; Tobia, Michael J; Sommer, Tobias; Obermayer, Klaus

    2014-07-01

    We derive a family of risk-sensitive reinforcement learning methods for agents, who face sequential decision-making tasks in uncertain environments. By applying a utility function to the temporal difference (TD) error, nonlinear transformations are effectively applied not only to the received rewards but also to the true transition probabilities of the underlying Markov decision process. When appropriate utility functions are chosen, the agents' behaviors express key features of human behavior as predicted by prospect theory (Kahneman & Tversky, 1979 ), for example, different risk preferences for gains and losses, as well as the shape of subjective probability curves. We derive a risk-sensitive Q-learning algorithm, which is necessary for modeling human behavior when transition probabilities are unknown, and prove its convergence. As a proof of principle for the applicability of the new framework, we apply it to quantify human behavior in a sequential investment task. We find that the risk-sensitive variant provides a significantly better fit to the behavioral data and that it leads to an interpretation of the subject's responses that is indeed consistent with prospect theory. The analysis of simultaneously measured fMRI signals shows a significant correlation of the risk-sensitive TD error with BOLD signal change in the ventral striatum. In addition we find a significant correlation of the risk-sensitive Q-values with neural activity in the striatum, cingulate cortex, and insula that is not present if standard Q-values are used.

  3. Methylenedioxypyrovalerone (MDPV mimics cocaine in its physiological and behavioral effects but induces distinct changes in NAc glucose

    Directory of Open Access Journals (Sweden)

    Ken Taro Wakabayashi

    2015-09-01

    Full Text Available Methylenedioxypyrovalerone (MDPV is generally considered to be a more potent cocaine-like psychostimulant, as it shares a similar pharmacological profile with cocaine and induces similar physiological and locomotor responses. Recently, we showed that intravenous cocaine induces rapid rise in nucleus accumbens (NAc glucose and established its relation to neural activation triggered by the peripheral drug actions. This study was conducted to find out whether MDPV, at a behaviorally equivalent dose, will share a similar pattern of NAc glucose dynamics. Using enzyme-based glucose sensors coupled with amperometery in freely moving rats, we found that MDPV tonically decreases NAc glucose levels, a response that is opposite to what we previously observed with cocaine. By analyzing Skin-Muscle temperature differentials, a valid measure of skin vascular tone, we found that MDPV induces vasoconstriction; a similar effect at the level of cerebral vessels could be responsible for the MDPV-induced decrease in NAc glucose. While cocaine also induced comparable, if not slightly stronger peripheral vasoconstriction, this effect was overpowered by local neural activity-induced vasodilation, resulting in rapid surge in NAc glucose. These results imply that cocaine-users may be more susceptible to addiction than MDPV-users due to the presence of an interoceptive signal (i.e. sensory cue, which may result in earlier and more direct reward detection. Additionally, while health complications arising from acute cocaine use are typically cardiovascular related, MDPV may be more dangerous to the brain due to uncompensated cerebral vasoconstriction.

  4. Methylenedioxypyrovalerone (MDPV) mimics cocaine in its physiological and behavioral effects but induces distinct changes in NAc glucose.

    Science.gov (United States)

    Wakabayashi, Ken T; Ren, Suelynn E; Kiyatkin, Eugene A

    2015-01-01

    Methylenedioxypyrovalerone (MDPV) is generally considered to be a more potent cocaine-like psychostimulant, as it shares a similar pharmacological profile with cocaine and induces similar physiological and locomotor responses. Recently, we showed that intravenous cocaine induces rapid rise in nucleus accumbens (NAc) glucose and established its relation to neural activation triggered by the peripheral drug actions. This study was conducted to find out whether MDPV, at a behaviorally equivalent dose, shares a similar pattern of NAc glucose dynamics. Using enzyme-based glucose sensors coupled with amperometery in freely moving rats, we found that MDPV tonically decreases NAc glucose levels, a response that is opposite to what we previously observed with cocaine. By analyzing Skin-Muscle temperature differentials, a valid measure of skin vascular tone, we found that MDPV induces vasoconstriction; a similar effect at the level of cerebral vessels could be responsible for the MDPV-induced decrease in NAc glucose. While cocaine also induced comparable, if not slightly stronger peripheral vasoconstriction, this effect was overpowered by local neural activity-induced vasodilation, resulting in rapid surge in NAc glucose. These results imply that cocaine-users may be more susceptible to addiction than MDPV-users due to the presence of an interoceptive signal (i.e., sensory cue), which may result in earlier and more direct reward detection. Additionally, while health complications arising from acute cocaine use are typically cardiovascular related, MDPV may be more dangerous to the brain due to uncompensated cerebral vasoconstriction.

  5. Sensitive innovation

    DEFF Research Database (Denmark)

    Søndergaard, Katia Dupret

    Present paper discusses sources of innovation as heterogenic and at times intangible processes. Arguing for heterogeneity and intangibility as sources of innovation originates from a theoretical reading in STS and ANT studies (e.g. Callon 1986, Latour 1996, Mol 2002, Pols 2005) and from field work...... in the area of mental health (Dupret Søndergaard 2009, 2010). The concept of sensitive innovation is developed to capture and conceptualise exactly those heterogenic and intangible processes. Sensitive innovation is therefore primarily a way to understand innovative sources that can be......, but are not necessarily, recognized and acknowledged as such in the outer organisational culture or by management. The added value that qualifies these processes to be defined as “innovative” are thus argued for along different lines than in more traditional innovation studies (e.g. studies that build on the classic...

  6. Ablation of the ID2 gene results in altered circadian feeding behavior, and sex-specific enhancement of insulin sensitivity and elevated glucose uptake in skeletal muscle and brown adipose tissue.

    Directory of Open Access Journals (Sweden)

    Deepa Mathew

    Full Text Available Inhibitor of DNA binding 2 (ID2 is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our earlier studies have demonstrated a role for ID2 in the input pathway, core clock function and output pathways of the mouse circadian system. We have also reported that Id2 null (Id2-/- mice are lean with low gonadal white adipose tissue deposits and lower lipid content in the liver. These results coincided with altered or disrupted circadian expression profiles of liver genes including those involved in lipid metabolism. In the present phenotypic study we intended to decipher, on a sex-specific basis, the role of ID2 in glucose metabolism and in the circadian regulation of activity, important components of energy balance. We find that Id2-/- mice exhibited altered daily and circadian rhythms of feeding and locomotor activity; activity profiles extended further into the late night/dark phase of the 24-hr cycle, despite mice showing reduced total locomotor activity. Also, male Id2-/- mice consumed a greater amount of food relative to body mass, and displayed less weight gain. Id2-/- females had smaller adipocytes, suggesting sexual-dimorphic programing of adipogenesis. We observed increased glucose tolerance and insulin sensitivity in male Id2-/- mice, which was exacerbated in older animals. FDG-PET analysis revealed increased glucose uptake by skeletal muscle and brown adipose tissue of male Id2-/- mice, suggesting increased glucose metabolism and thermogenesis in these tissues. Reductions in intramuscular triacylglycerol and diacylglycerol were detected in male Id2-/- mice, highlighting its possible mechanistic role in enhanced insulin sensitivity in these mice. Our findings indicate a role for ID2 as a regulator of glucose and lipid metabolism, and in the circadian control of feeding/locomotor behavior; and contribute to the understanding of the development of obesity and diabetes, particularly in shift work

  7. Behavioral response of resistant and sensitive Pseudomonas ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-18

    Jul 18, 2008 ... structure of nucleic acids and proteins or interference with oxidative ... cyanobacteria (Malik, 2004; Ünaldi et al., 2003,. Piotrowska-Seget et al., 2005). ... heavy metal-treated cells (Pessoa-de-Franca et al.,. 2002). The main ...

  8. In chemico evaluation of prohapten skin sensitizers: behavior of 2-methoxy-4-(¹³C)methylphenol in the peroxidase peptide reactivity assay (PPRA) as an alternative to animal testing.

    Science.gov (United States)

    Merckel, Fabien; Giménez-Arnau, Elena; Gerberick, G Frank; Lepoittevin, Jean-Pierre

    2013-04-26

    In chemico methods, based on the assessment of a hapten's reactivity toward peptides, have been proposed as alternative methods for the assessment of the skin sensitizing potential of chemicals. However, even with these approaches showing promise, a major drawback is the activation of prohaptens, i.e. molecules needing a metabolic activation to become reactive and therefore sensitizing. Recently, it has been proposed to couple an enzymatic activation step based on horseradish peroxidase (HRP)/hydrogen peroxide to such peptide reactivity assays. To evaluate this approach, the behavior of 2-methoxy-4-methylphenol (2M4MP), reported as a moderate sensitizer according to the Local Lymph Node Assay (LLNA), has been investigated in this assay. To follow the reaction with the peptides and characterize more easily intermediates and adducts, the molecule was first (13)C isotopically substituted at the most probable reactive position. When 2M4MP was incubated with HRP/H2O2 in a mixture PBS (pH 7.4, 0.1M)/acetonitrile 2:1, two main products were formed deriving from the formation of a quinone methide 2M4MQ subsequently trapped by either H2O2 or H2O to form a benzylic hydroperoxide or alcohol, respectively. When nucleophiles such as GSH or a peptide containing a cysteine residue (Pep-Cys) were present in the reaction medium, the quinone methide 2M4MQ was trapped by the more nucleophilic thiol function to form thio-adducts. No modifications of 2M4MP were observed when the same reactions were carried out without HRP confirming that the activation of the molecule was enzyme related. Amino nucleophiles were shown to be far less reactive towards the quinone methide 2M4MQ with only tiny formation of adducts with lysine or arginine side chains. In addition we demonstrated that the same enzymatic activation could also take place in a microemulsion based on sodium dodecyl sulfate/tert-butanol/chloroform/buffer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Study on in vitro drug release behavior P (EG-MAA-MEG) pH sensitive hydrogels%P(CE-MAA-MEG)pH敏感性水凝胶的体外释放药物行为考察

    Institute of Scientific and Technical Information of China (English)

    郑施施; 王增寿

    2012-01-01

    目的:研究一种P(EG-MAA-MEG) pH敏感性水凝胶在口服药物传输体系中的应用.方法:本文采用自由基聚合方法制备一种具有良好pH响应性能的水凝胶,并对其pH响应性能进行相关的表征.以维生素B12(VB12)为模型药物,考察载药水凝胶在不同pH环境条件下(pH 1.2和pH 7.4)的药物释放行为.结果:P(EG-MAA-MEG) pH敏感水凝胶具有明显的孔洞结构和良好的pH响应性能,在中性磷酸盐缓冲溶液(pH 7.4)中吸水率显著大于在酸性溶液(pH 1.2)中的吸水率.装载维生素B12的pH敏感水凝胶在中性磷酸盐缓冲溶液(pH 7.4)中的8h的药物累计释放率达到50%,而在酸性溶液(pH1.2)中的8h的药物累计释放率只有30%左右.结论:可生物降解P(EG-MAA-MEG) pH敏感性水凝胶具有良好的pH敏感性和药物缓控释性能,在口服结肠靶向给药体系中有一定的应用前景.%OBJECTIVE To study of the P (EG-MAA-MEG) pH sensitive hydrogels for the application in oral drug delivery system. METHODS Using free radical polymerization method to develop a good pH response properties of the hydrogel, and the pH response performance were characterized. Using vitamin B12 as a model drug, the dnug release behavior of hydrogel at different pH conditions (pH I. 2 and pH 7. 4) was examined. RESULTS P (EG-MAA-MEG) pH sensitive hydrogels with visible hole structure and good pH response performance,in neutral phosphate buffer solution (pH 7. 4) in water absorption rate was significantly higher than that in acidic solution ( pH I, 2) in the rate of water absorption . Containing vitamin B12 pH sensitive hydrogels in neutral phosphate buffer solution ( pH 7. 4) ,the 8 h drug accumulative release rate reached 50%,m an acidic solution ( pH 1. 2),the 8 h drug accumulative release rate of only about 30% . CONCLUSION Biodegradable P (EG-MAA-MEG) pH sensitive hydrogel has good pH sensitivity and controlled drug release properties, in oral drug delivery system it has

  10. Anxiolytic-like actions of toluene in the burying behavior and plus-maze tests: differences in sensitivity between 5-HT(1B) knockout and wild-type mice.

    Science.gov (United States)

    López-Rubalcava, C; Hen, R; Cruz, S L

    2000-10-01

    This paper compares the anxiolytic-like actions of toluene in two anxiety paradigms, the burying behavior and plus-maze tests, in 5-HT(1B) knockout (KO) and 129/Sv-ter wild-type (WT) mice. Static exposures were conducted in 29-l gas chromatographic jars. Animals were exposed to toluene (0, 1000, 2000 or 4000 ppm; n=8-12, each) for 30 min, and immediately after, tested in one of the anxiety paradigms. Motor coordination was evaluated in the rota-rod test in independent groups of mice. Toluene produced a dose-dependent decrease in anxiety-like levels in both anxiety paradigms and in both the strains. However, toluene exerted its effects at lower concentrations in KO mice than in the WT strain. These results cannot be attributed to a decrease in motor coordination since all the animals behaved similarly in the rota-rod test, regardless of the treatment. To discard any inherent difference in the nociception threshold between strains, mice were tested in the hot plate immediately after being exposed to either air or toluene. Toluene increased nociception in a similar fashion in both the strains. Our results suggest that 5-HT(1B) KO mice are more sensitive to those of toluene's actions related to anxiety, but not to those related with motor coordination or nociception. Data are discussed in terms of toluene's mechanisms of action and on differences between WT and KO animals.

  11. Sensitivity, Recalculated

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, J. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-11-07

    Prior to this study, the sensitivity in nEXO was calculated using an approximate method that does not provide 90% coverage. I find it useful to understand the confidence level of a limit by focusing on the confidence level as a property of the method used to find the limit.A particular method (algorithm,formula) is applied to an experiment to produce a limit. That experiment was conducted in a particular universe with certain values of the physical parameters. We’d like a method than produces a correct limit for 90% of the experiments that could run. We also want that to be true for every universe—that is, regardless of the physical parameter value, the method should still produce a correct limit 90% of the time.

  12. Beyond sensitivity

    DEFF Research Database (Denmark)

    Stott, Iain; Hodgson, David James; Townley, Stuart

    2012-01-01

    1. Perturbation analyses of population models are integral to population management: such analyses evaluate how changes in vital rates of members of the population translate to changes in population dynamics. Sensitivity and elasticity analyses of long-term (asymptotic) growth are popular...... formulae for the transfer function of population inertia, which describes nonlinear perturbation curves of transient population dynamics. The method comfortably fits into wider frameworks for analytical study of transient dynamics, and for perturbation analyses that use the transfer function approach. 3....... We use case studies to illustrate how the transfer function of population inertia may be used in population management. These show that strategies based solely on asymptotic perturbation analyses can cause undesirable transient dynamics and/ or fail to exploit desirable transient dynamics...

  13. Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior.

    Science.gov (United States)

    Friedman, Alexander; Lax, Elad; Dikshtein, Yahav; Abraham, Lital; Flaumenhaft, Yakov; Sudai, Einav; Ben-Tzion, Moshe; Ami-Ad, Lavi; Yaka, Rami; Yadid, Gal

    2010-11-01

    The lateral habenula (LHb) is critical for modulation of negative reinforcement, punishment and aversive responses. In light of the success of deep-brain-stimulation (DBS) in the treatment of neurological disorders, we explored the use of LHb DBS as a method of intervention in cocaine self-administration, extinction, and reinstatement in rats. An electrode was implanted into the LHb and rats were trained to self-administer cocaine (21 days; 0.25-1 mg/kg) until they achieved at least three days of stable performance (as measured by daily recordings of active lever presses in self-administration cages). Thereafter, rats received DBS in the presence or absence of cocaine. DBS reduced cocaine seeking behavior during both self-administration and extinction training. DBS also attenuated the rats' lever presses following cocaine reinstatement (5-20 mg/kg) in comparison to sham-operated rats. These results were also controlled by the assessment of physical performance as measured by water self-administration and an open field test, and by evaluation of depressive-like manifestations as measured by the swim and two-bottles-choice tests. In contrast, LHb lesioned rats demonstrated increased cocaine seeking behavior as demonstrated by a delayed extinction response. In the ventral tegmental area, cocaine self-administration elevated glutamatergic receptor subunits NR1 and GluR1 and scaffolding protein PSD95, but not GABA(A)β, protein levels. Following DBS treatment, levels of these subunits returned to control values. We postulate that the effect of both LHb modulation and LHb DBS on cocaine reinforcement may be via attenuation of the cocaine-induced increase in glutaminergic input to the VTA.

  14. 温敏性三元共聚水凝胶溶胀及消溶胀行为%Swelling and Deswelling Behavior of Temperature-Sensitive Terpolymer Hydrogels

    Institute of Scientific and Technical Information of China (English)

    刘维俊; 吉家俊; 朱信龙; 曲华军; 沈琼

    2012-01-01

    Terpolymer hydrogels of poly(N-isopropylacrylamide-co-chitosan-co-methacrylic acid)[P(NIPAM-co-CS-co-MAA)] were prepared by free radical solution polymerization at room temperature.The structure and swelling of the hydrogels were characterized by Fourier transform infrared spectroscopy and gravimetric method.The results indicate the swelling behavior of higher cross-linking hydrogels accords with non-Fickian diffusion mechanism,and the copolymer occurres prominently deswelling as temperature above 35 ℃.An obvious effect of monomers composition on swelling was confirmed by means of swelling experiments,and the swelling and deswelling transition arose from MAA to the terpolymer are greater than from CS under the same mass of MAA and CS monomers.For the swelling behavior of the hydrogels in various pH solutions,the swelling degree in alkaline solution exceeds in acidic medium,but it becomes bad in about pH=5.0 solution.This fact indicates that the hydrogels possess an anomalous pH-sensitivity,which differs from conventional methacrylic acid hydrogels,and the deswelling process is in very good agreement with first-ordered kinetics.%采用自由基溶液聚合法,室温下制备了聚(N-异丙基丙烯酰胺-co-壳聚糖-co-甲基丙烯酸)[P(NIPAM-co-CS-co-MAA)]三元共聚水凝胶,以红外光谱及质量法对凝胶结构和溶胀性进行了表征。结果表明,高交联凝胶溶胀符合non-Fickian扩散;温度高于35℃时溶胀的共聚凝胶均发生明显收缩;相同甲基丙烯酸(MAA)和壳聚糖(CS)单体用量,MAA对凝胶溶胀和消溶胀影响大于CS。不同pH溶液中的溶胀碱性时比酸性条件下更大,pH=5.0左右较差,显示与传统甲基丙烯酸系水凝胶不同的pH敏感性,其消溶胀动力学满足一级动力学方程。

  15. Gluten Sensitivity.

    Science.gov (United States)

    Catassi, Carlo

    2015-01-01

    Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). The prevalence of NCGS is not clearly defined yet. Indirect evidence suggests that NCGS is slightly more common than CD, the latter affecting around 1% of the general population. NCGS has been mostly described in adults, particularly in females in the age group of 30-50 years; however, pediatric case series have also been reported. Since NCGS may be transient, gluten tolerance needs to be reassessed over time in patients with NCGS. NCGS is characterized by symptoms that usually occur soon after gluten ingestion, disappear with gluten withdrawal, and relapse following gluten challenge within hours/days. The 'classical' presentation of NCGS is a combination of irritable bowel syndrome-like symptoms, including abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), and systemic manifestations such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis (eczema or skin rash), depression, and anemia. In recent years, several studies explored the relationship between the ingestion of gluten-containing food and the appearance of neurological and psychiatric disorders/symptoms like ataxia, peripheral neuropathy, schizophrenia, autism, depression, anxiety, and hallucinations (so-called gluten psychosis). The diagnosis of NCGS should be considered in patients with persistent intestinal and/or extraintestinal complaints showing a normal result of the CD and WA serological markers on a gluten-containing diet, usually reporting worsening of symptoms after eating gluten-rich food. NCGS should not be an exclusion diagnosis only. Unfortunately, no biomarker is sensitive and specific enough for diagnostic purposes; therefore, the diagnosis of NCGS is currently based on

  16. Surveillance Metrics Sensitivity Study

    Energy Technology Data Exchange (ETDEWEB)

    Bierbaum, R; Hamada, M; Robertson, A

    2011-11-01

    In September of 2009, a Tri-Lab team was formed to develop a set of metrics relating to the NNSA nuclear weapon surveillance program. The purpose of the metrics was to develop a more quantitative and/or qualitative metric(s) describing the results of realized or non-realized surveillance activities on our confidence in reporting reliability and assessing the stockpile. As a part of this effort, a statistical sub-team investigated various techniques and developed a complementary set of statistical metrics that could serve as a foundation for characterizing aspects of meeting the surveillance program objectives. The metrics are a combination of tolerance limit calculations and power calculations, intending to answer level-of-confidence type questions with respect to the ability to detect certain undesirable behaviors (catastrophic defects, margin insufficiency defects, and deviations from a model). Note that the metrics are not intended to gauge product performance but instead the adequacy of surveillance. This report gives a short description of four metrics types that were explored and the results of a sensitivity study conducted to investigate their behavior for various inputs. The results of the sensitivity study can be used to set the risk parameters that specify the level of stockpile problem that the surveillance program should be addressing.

  17. Activation of D1/5 Dopamine Receptors: A Common Mechanism for Enhancing Extinction of Fear and Reward-Seeking Behaviors.

    Science.gov (United States)

    Abraham, Antony D; Neve, Kim A; Lattal, K Matthew

    2016-07-01

    Dopamine is critical for many processes that drive learning and memory, including motivation, prediction error, incentive salience, memory consolidation, and response output. Theories of dopamine's function in these processes have, for the most part, been developed from behavioral approaches that examine learning mechanisms in appetitive tasks. A parallel and growing literature indicates that dopamine signaling is involved in consolidation of memories into stable representations in aversive tasks such as fear conditioning. Relatively little is known about how dopamine may modulate memories that form during extinction, when organisms learn that the relation between previously associated events is severed. We investigated whether fear and reward extinction share common mechanisms that could be enhanced with dopamine D1/5 receptor activation. Pharmacological activation of dopamine D1/5 receptors (with SKF 81297) enhanced extinction of both cued and contextual fear. These effects also occurred in the extinction of cocaine-induced conditioned place preference, suggesting that the observed effects on extinction were not specific to a particular type of procedure (aversive or appetitive). A cAMP/PKA biased D1 agonist (SKF 83959) did not affect fear extinction, whereas a broadly efficacious D1 agonist (SKF 83822) promoted fear extinction. Together, these findings show that dopamine D1/5 receptor activation is a target for the enhancement of fear or reward extinction.

  18. Behavior subtraction

    Science.gov (United States)

    Jodoin, Pierre-Marc; Saligrama, Venkatesh; Konrad, Janusz

    2008-01-01

    Network video cameras, invented in the last decade or so, permit today pervasive, wide-area visual surveillance. However, due to the vast amounts of visual data that such cameras produce human-operator monitoring is not possible and automatic algorithms are needed. One monitoring task of particular interest is the detection of suspicious behavior, i.e., identification of individuals or objects whose behavior differs from behavior usually observed. Many methods based on object path analysis have been developed to date (motion detection followed by tracking and inferencing) but they are sensitive to motion detection and tracking errors and are also computationally complex. We propose a new surveillance method capable of abnormal behavior detection without explicit estimation of object paths. Our method is based on a simple model of video dynamics. We propose one practical implementation of this general model via temporal aggregation of motion detection labels. Our method requires little processing power and memory, is robust to motion segmentation errors, and general enough to monitor humans, cars or any other moving objects in uncluttered as well as highly-cluttered scenes. Furthermore, on account of its simplicity, our method can provide performance guarantees. It is also robust in harsh environments (jittery cameras, rain/snow/fog).

  19. Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats.

    Directory of Open Access Journals (Sweden)

    Seol Ah Kim

    Full Text Available Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles or 200 (for Pacinian corpuscles Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.

  20. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; Fennis, Bob M.; Vet, De Emely; Ridder, De Denise T.D.

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  1. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.|info:eu-repo/dai/nl/304823023; Fennis, Bob M.; De Vet, Emely; De Ridder, Denise T D

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  2. Crack Cocaine-Induced Cardiac Conduction Abnormalities Are Reversed by Sodium Bicarbonate Infusion

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Miranda

    2013-01-01

    Full Text Available We report a dramatic case of a 19-year-old man with crack cocaine overdose with important clinical complications as cardiac arrest due to ventricular fibrillation and epileptics status. During this intoxication, electrocardiographic abnormalities similar to those found in tricyclic antidepressant poisoning were observed, and they were reversed by intravenous sodium bicarbonate infusion.

  3. Surgical Management of Levamisole-Adulterated Cocaine Induced Soft Tissue Necrosis: Case Study and Treatment Algorithm.

    Science.gov (United States)

    Mcevenue, Giancarlo; Brichacek, Michael; Logsetty, Sarvesh; Shahrokhi, Shar

    2016-08-18

    Levamisole is an increasingly common cocaine adulterant that can cause severe and rapid onset cutaneous vasculitis in humans. While most cases may be managed conservatively, we describe a series of patients in whom the extent of skin and soft tissue necrosis mandated surgical intervention. A retrospective review of all patients admitted to one of two regional burn centers between 2006 and 2016 for soft tissue necrosis after exposure to levamisole-adulterated cocaine was included in our study. Ten patients, majority female (9/10) with an average age of 43.4 years (range 31-57), were included. Cocaine usage before presentation averaged 6 days (range 1-14). Presenting complaints consisted of arthralgia (5/10), fever (7/10), and purpuric lesions (10/10). Average TBSA involvement was 23.5% (range 4-70). Immunological testing revealed pANCA+ in 8 of 10 and cANCA+ in 4 of 8 patients. Operative intervention occurred by postadmission day 11.6 (range 3-30). The mean number of operations required was 3 (range 2-6); length of stay averaged 46.8 days (range 14-120); and survival to discharge was 100% (10/10). To our knowledge, this is the largest case study detailing the surgical management of levamisole-associated skin necrosis. Additionally, we describe the most extensive case of this disease process at 70% TBSA involvement. Based on our experience, we recommend waiting for purpuric rash resolution and soft tissue necrosis to be fully demarcated before fascial debridement and then staged skin grafting with allograft followed by autograft.

  4. Levamisole-adulterated cocaine induced skin necrosis of nose, ears, and extremities: Case report

    Science.gov (United States)

    Jiron, Jose L.; Lin, Ho-Sheng; Folbe, Adam J.

    2014-01-01

    Levamisole is an immunomodulatory and antihelminthic drug, previously removed from the United States market, and now estimated to be present in the vast majority of cocaine distributed in the United States. Levamisole-adulterated cocaine (LAC) exposure can result in neutropenia, thrombocytopenia, and vasculitis with a predilection for subsites of the face. The objective of this review is to increase awareness among otolaryngologists of the manifestations of LAC exposure. We present the case of a 33-year-old woman with a history of cocaine use, consulted for purpuric, necrotic lesions of the nose, cheeks, and ears, with accompanying leukopenia, thrombocytopenia, and positive antineutrophil cytoplasmic antibodies (ANCA). The effects of levamisole are immune mediated, with antibodies directed against neutrophils causing neutropenia, and vasculitis caused by antibody deposition or secondary to induction of antiphospholipid antibodies causing thrombosis. LAC exposure can be differentiated from other similar appearing pathologies by evaluating serology for specific ANCA. The most important treatment is cessation of cocaine use, which most often results in complete resolution of symptoms. Awareness of the presentation, complications, and treatment of LAC exposure may be especially important for otolaryngologists, who may be one of the firsts to evaluate an affected patient. PMID:25565048

  5. Acute total sleep deprivation potentiates cocaine-induced hyperlocomotion in mice

    OpenAIRE

    Berro, Laís Fernanda; Santos, Renan [UNIFESP; Hollais, André Willian [UNIFESP; Wuo-Silva, Raphael; Fukushiro, Daniela Fukue [UNIFESP; Mári-Kawamoto, Elisa; Costa, Jacqueline Menezes [UNIFESP; Trombin, Thaís Fernanda [UNIFESP; Patti, Camila de Lima [UNIFESP; Grapiglia, Stephanie Berzin [UNIFESP; Tufik, Sergio; Andersen, Monica Levy [UNIFESP; Frussa Filho, Roberto [UNIFESP

    2014-01-01

    Sleep deprivation is common place in modern society. Nowadays, people tend to self-impose less sleep in order to achieve professional or social goals. in the social context, late-night parties are frequently associated with higher availability of recreational drugs with abuse potential. Physiologically, all of these drugs induce an increase in dopamine release in the mesolimbic dopaminergic system, which leads to hyperlocomotion in rodents. Sleep deprivation also seems to play an important ro...

  6. Cocaine-induced Modification of Synaptic Plasticity in Rat Medial Prefrontal Cortex

    OpenAIRE

    Lu, Hui

    2009-01-01

    Medial prefrontal cortex (mPFC) is involved in relapse after withdrawal for cocaine exposure, but changes in synaptic function and plasticity in the mPFC during the period of withdrawal remain largely unknown. After the termination of repeated cocaine treatments in rats, I observed a gradual enhancement in the susceptibility of excitatory synapses on layer V mPFC pyramidal neurons to activity-induced long-term potentiation (LTP). This enhanced synaptic plasticity could be attributed to a grad...

  7. The neural encoding of cocaine-induced devaluation in the ventral pallidum.

    Science.gov (United States)

    Chan, Chung-Lung; Wheeler, Daniel S; Wheeler, Robert A

    2016-04-01

    Cocaine experience affects motivation structures such as the nucleus accumbens (NAc) and its major output target, the ventral pallidum (VP). Previous studies demonstrated that both NAc activity and hedonic responses change reliably as a taste cue comes to predict cocaine availability. Here we extended this investigation to examine drug-experience induced changes in hedonic encoding in the VP. VP activity was first characterized in adult male Sprague-Dawley rats in response to intraoral infusions of palatable saccharin and unpalatable quinine solutions. Next, rats received 7 daily pairings of saccharin that predicted either a cocaine (20mg/kg, ip) or saline injection. Finally, the responses to saccharin and quinine were again assessed. Of 109 units recorded in 11 rats that received saccharin-cocaine pairings, 71% of responsive units significantly reduced firing rate during saccharin infusions and 64% increased firing rate during quinine exposure. However, as saccharin came to predict cocaine, and elicited aversive taste reactivity, VP responses changed to resemble quinine. After conditioning, 70% of saccharin-responsive units increased firing rate. Most units that encoded the palatable taste (predominantly reduced firing rate) were located in the anterior VP, while most units that were responsive to aversive tastes were located in the posterior VP. This study reveals an anatomical complexity to the nature of hedonic encoding in the VP.

  8. Reinforcement Sensitivity Underlying Treatment-Seeking Smokers’ Affect, Smoking Reinforcement Motives, and Affective Responses

    OpenAIRE

    Cui, Yong; Robinson, Jason D.; Engelmann, Jeffrey M.; Lam, Cho Y.; Minnix, Jennifer A.; Karam-Hage, Maher; Wetter, David W.; Dani, John A; Kosten, Thomas R.; Cinciripini, Paul M.

    2015-01-01

    Nicotine dependence has been suggested to be related to reinforcement sensitivity, which encompasses behavioral predispositions either to avoid aversive (behavioral inhibition) or to approach appetitive (behavioral activation) stimuli. Reinforcement sensitivity may shape motives for nicotine use and offer potential targets for personalized smoking cessation therapy. However, little is known regarding how reinforcement sensitivity is related to motivational processes implicated in the maintena...

  9. Auditory sensitivity in aquatic animals.

    Science.gov (United States)

    Lucke, Klaus; Popper, Arthur N; Hawkins, Anthony D; Akamatsu, Tomonari; André, Michel; Branstetter, Brian K; Lammers, Marc; Radford, Craig A; Stansbury, Amanda L; Aran Mooney, T

    2016-06-01

    A critical concern with respect to marine animal acoustics is the issue of hearing "sensitivity," as it is widely used as a criterion for the onset of noise-induced effects. Important aspects of research on sensitivity to sound by marine animals include: uncertainties regarding how well these species detect and respond to different sounds; the masking effects of man-made sounds on the detection of biologically important sounds; the question how internal state, motivation, context, and previous experience affect their behavioral responses; and the long-term and cumulative effects of sound exposure. If we are to better understand the sensitivity of marine animals to sound we must concentrate research on these questions. In order to assess population level and ecological community impacts new approaches can possibly be adopted from other disciplines and applied to marine fauna.

  10. Decrease of D2 receptor binding but increase in D2-stimulated G-protein activation, dopamine transporter binding and behavioural sensitization in brains of mice treated with a chronic escalating dose 'binge' cocaine administration paradigm.

    Science.gov (United States)

    Bailey, A; Metaxas, A; Yoo, J H; McGee, T; Kitchen, I

    2008-08-01

    Understanding the neurobiology of the transition from initial drug use to excessive drug use has been a challenge in drug addiction. We examined the effect of chronic 'binge' escalating dose cocaine administration, which mimics human compulsive drug use, on behavioural responses and the dopaminergic system of mice and compared it with a chronic steady dose (3 x 15 mg/kg/day) 'binge' cocaine administration paradigm. Male C57BL/6J mice were injected with saline or cocaine in an escalating dose paradigm for 14 days. Locomotor and stereotypy activity were measured and quantitative autoradiographic mapping of D(1) and D(2) receptors, dopamine transporters and D(2)-stimulated [(35)S]GTPgammaS binding was performed in the brains of mice treated with this escalating and steady dose paradigm. An initial sensitization to the locomotor effects of cocaine followed by a dose-dependent increase in the duration of the locomotor effect of cocaine was observed in the escalating but not the steady dose paradigm. Sensitization to the stereotypy effect of cocaine and an increase in cocaine-induced stereotypy score was observed from 3 x 20 to 3 x 25 mg/kg/day cocaine. There was a significant decrease in D(2) receptor density, but an increase in D(2)-stimulated G-protein activity and dopamine transporter density in the striatum of cocaine-treated mice, which was not observed in our steady dose paradigm. Our results document that chronic 'binge' escalating dose cocaine treatment triggers profound behavioural and neurochemical changes in the dopaminergic system, which might underlie the transition from drug use to compulsive drug use associated with addiction, which is a process of escalation.

  11. Culture-sensitive psychotraumatology

    Directory of Open Access Journals (Sweden)

    Ulrich Schnyder

    2016-07-01

    Full Text Available Background: Although there is some evidence of the posttraumatic stress disorder (PTSD construct's cross cultural validity, trauma-related disorders may vary across cultures, and the same may be true for treatments that address such conditions. Experienced therapists tailor psychotherapy to each patient's particular situation, to the nature of the patient's psychopathology, to the stage of therapy, and so on. In addition, culture-sensitive psychotherapists try to understand how culture enhances the meaning of their patient's life history, the cultural components of their illness and help-seeking behaviors, as well as their expectations with regard to treatment. We cannot take for granted that all treatment-seeking trauma survivors speak our language or share our cultural values. Therefore, we need to increase our cultural competencies. Methods: The authors of this article are clinicians and/or researchers from across the globe, working with trauma survivors in various settings. Each author focused on one or more specific cultural aspects of working with trauma survivors and highlighted the following aspects. Results: As a result of culture-specific individual and collective meanings linked to trauma and trauma-related disorders survivors may be exposed to (self-stigma in the aftermath of trauma. Patients who are reluctant to talk about their traumatic experiences may instead be willing to write or use other ways of accessing the painful memories such as drawing. In other cultures, community and family cohesion are crucial elements of recovery. While awareness of culture-specific aspects is important, we also need to beware of premature cultural stereotyping. When disseminating empirically supported psychotherapies for PTSD across cultures, a number of additional challenges need to be taken into account: many low and middle income countries have very limited resources available and suffer from a poor health infrastructure. Conclusions: In summary

  12. Culture-sensitive psychotraumatology

    Science.gov (United States)

    Schnyder, Ulrich; Bryant, Richard A.; Ehlers, Anke; Foa, Edna B.; Hasan, Aram; Mwiti, Gladys; Kristensen, Christian H.; Neuner, Frank; Oe, Misari; Yule, William

    2016-01-01

    Background Although there is some evidence of the posttraumatic stress disorder (PTSD) construct's cross cultural validity, trauma-related disorders may vary across cultures, and the same may be true for treatments that address such conditions. Experienced therapists tailor psychotherapy to each patient's particular situation, to the nature of the patient's psychopathology, to the stage of therapy, and so on. In addition, culture-sensitive psychotherapists try to understand how culture enhances the meaning of their patient's life history, the cultural components of their illness and help-seeking behaviors, as well as their expectations with regard to treatment. We cannot take for granted that all treatment-seeking trauma survivors speak our language or share our cultural values. Therefore, we need to increase our cultural competencies. Methods The authors of this article are clinicians and/or researchers from across the globe, working with trauma survivors in various settings. Each author focused on one or more specific cultural aspects of working with trauma survivors and highlighted the following aspects. Results As a result of culture-specific individual and collective meanings linked to trauma and trauma-related disorders survivors may be exposed to (self-)stigma in the aftermath of trauma. Patients who are reluctant to talk about their traumatic experiences may instead be willing to write or use other ways of accessing the painful memories such as drawing. In other cultures, community and family cohesion are crucial elements of recovery. While awareness of culture-specific aspects is important, we also need to beware of premature cultural stereotyping. When disseminating empirically supported psychotherapies for PTSD across cultures, a number of additional challenges need to be taken into account: many low and middle income countries have very limited resources available and suffer from a poor health infrastructure. Conclusions In summary, culture-sensitive

  13. Associations between sensitivity to punishment, sensitivity to reward, and gambling.

    Science.gov (United States)

    Gaher, Raluca M; Hahn, Austin M; Shishido, Hanako; Simons, Jeffrey S; Gaster, Sam

    2015-03-01

    The majority of individuals gamble during their lifetime; however only a subset of these individuals develops problematic gambling. Gray's Reinforcement Sensitivity Theory may be relevant to understanding gambling problems. Differences in sensitivity to punishments and rewards can influence an individual's behavior and may be pertinent to the development of gambling problems. This study examined the functional associations between sensitivity to punishment (SP), sensitivity to reward (SR), and gambling problems in a sample of 2254 college students. Zero-inflated negative binomial regression was used to predict gambling problems as well as the absence of gambling problems. Gambling problems were hypothesized to be positively associated with SR and inversely associated with SP. In addition, SP was hypothesized to moderate the association between SR and gambling problems, attenuating the strength of the association. As hypothesized, SR was positively associated with gambling problems. However, SP did not moderate the relationship between SR and gambling problems. SP did, however, moderate the relationship between SR and the likelihood of never experiencing gambling problems. The results demonstrate that individual differences in SP and SR are functionally associated with gambling problems.

  14. Neuroscientific Measures of Covert Behavior

    Science.gov (United States)

    Ortu, Daniele

    2012-01-01

    In radical behaviorism, the difference between overt and covert responses does not depend on properties of the behavior but on the sensitivity of the measurement tools employed by the experimenter. Current neuroscientific research utilizes technologies that allow measurement of variables that are undetected by the tools typically used by behavior…

  15. Neuroscientific Measures of Covert Behavior

    Science.gov (United States)

    Ortu, Daniele

    2012-01-01

    In radical behaviorism, the difference between overt and covert responses does not depend on properties of the behavior but on the sensitivity of the measurement tools employed by the experimenter. Current neuroscientific research utilizes technologies that allow measurement of variables that are undetected by the tools typically used by behavior…

  16. Interference comb-spectroscopy with increasing sensitivity

    Science.gov (United States)

    Pulkin, Sergey; Borisov, Evgenii; Balabas, Michail; Uvarova, Svetlana; Shevtzov, Vladimir; Kalinichev, Alexei; Shoev, Vladislav; Venediktov, Dmitrii; Venediktov, Vladimir

    2016-10-01

    The paper considers the use of holographic interferometer for hologram recording of the wide spectrum from the comb - generator of the femtosecond laser was applied for illuminating of Michelson interferometer with atomic vapor. The behavior of spectral interference fringes on the exit slit of spectrograph reflects the behavior of nonlinear refractive index. The method of holographic interferometry with increasing sensitivity using phase modulator was applied for digital hologram processing.

  17. Risk-sensitivity in sensorimotor control

    Directory of Open Access Journals (Sweden)

    Daniel A. Braun

    2011-01-01

    Full Text Available Recent advances in theoretical neuroscience suggest that motor control can be considered as a continuous decision-making process in which uncertainty plays a key role. Decision-makers can be risk-sensitive with respect to this uncertainty in that they may not only consider the average payoff of an outcome, but also consider the variability of the payoffs. Although such risk-sensitivity is a well-established phenomenon in psychology and economics, it has been much less studied in motor control. In fact, leading theories of motor control, such as optimal feedback control, assume that motor behaviors can be explained as the optimization of a given expected payoff or cost. Here we review evidence that humans exhibit risk-sensitivity in their motor behaviors, thereby demonstrating sensitivity to the variability of ‘motor costs’. Furthermore, we discuss how risk-sensitivity can be incorporated into optimal feedback control models of motor control. We conclude that risk-sensitivity is an important concept in understanding individual motor behavior under uncertainty.

  18. Habituation, sensitization and Pavlovian conditioning

    Directory of Open Access Journals (Sweden)

    Münire Özlem Çevik

    2014-02-01

    Full Text Available In this brief review, I argue that the impact of a stimulus on behavioral control increase as the distance of the stimulus to the body decreases. Habituation, i.e., decrement in response intensity repetition of the triggering stimulus, is the default state for sensory processing, and the likelihood of habituation is higher for distal stimuli. Sensitization, i.e., increment in response intensity upon stimulus repetition, occurs in a state dependent manner for proximal stimuli that make direct contact with the body. In Pavlovian conditioning paradigms, the US is always a more proximal stimulus than the CS. The mechanisms of associative and non-associative learning are not independent. CS-US pairings lead to formation of associations if sensitizing modulation from a proximal US prevents the habituation for a distal anticipatory CS.

  19. Contextual sensitivity in scientific reproducibility.

    Science.gov (United States)

    Van Bavel, Jay J; Mende-Siedlecki, Peter; Brady, William J; Reinero, Diego A

    2016-06-07

    In recent years, scientists have paid increasing attention to reproducibility. For example, the Reproducibility Project, a large-scale replication attempt of 100 studies published in top psychology journals found that only 39% could be unambiguously reproduced. There is a growing consensus among scientists that the lack of reproducibility in psychology and other fields stems from various methodological factors, including low statistical power, researcher's degrees of freedom, and an emphasis on publishing surprising positive results. However, there is a contentious debate about the extent to which failures to reproduce certain results might also reflect contextual differences (often termed "hidden moderators") between the original research and the replication attempt. Although psychologists have found extensive evidence that contextual factors alter behavior, some have argued that context is unlikely to influence the results of direct replications precisely because these studies use the same methods as those used in the original research. To help resolve this debate, we recoded the 100 original studies from the Reproducibility Project on the extent to which the research topic of each study was contextually sensitive. Results suggested that the contextual sensitivity of the research topic was associated with replication success, even after statistically adjusting for several methodological characteristics (e.g., statistical power, effect size). The association between contextual sensitivity and replication success did not differ across psychological subdisciplines. These results suggest that researchers, replicators, and consumers should be mindful of contextual factors that might influence a psychological process. We offer several guidelines for dealing with contextual sensitivity in reproducibility.

  20. Sensitization and habituation regulate reinforcer effectiveness.

    Science.gov (United States)

    McSweeney, Frances K; Murphy, Eric S

    2009-09-01

    We argue that sensitization and habituation occur to the sensory properties of reinforcers when those reinforcers are presented repeatedly or for a prolonged time. Sensitization increases, and habituation decreases, the ability of a reinforcer to control behavior. Supporting this argument, the rate of operant responding changes systematically within experimental sessions even when the programmed rate of reinforcement is held constant across the session. These within-session changes in operant responding are produced by repeated delivery of the reinforcer, and their empirical characteristics correspond to the characteristics of behavior undergoing sensitization and habituation. Two characteristics of habituation (dishabituation, stimulus specificity) are particularly useful in separating habituation from alternative explanations. Arguing that habituation occurs to reinforcers expands the domain of habituation. The argument implies that habituation occurs to biologically important, not just to neutral, stimuli. The argument also implies that habituation may be observed in "voluntary" (operant), not just in reflexive, behavior. Expanding the domain of habituation has important implications for understanding operant and classical conditioning. Habituation may also contribute to the regulation of motivated behaviors. Habituation provides a more accurate and a less cumbersome explanation for motivated behaviors than homeostasis. Habituation also has some surprising, and easily testable, implications for the control of motivated behaviors.

  1. How sensitizing is chlorocresol?

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Hamann, K

    1984-01-01

    Chlorocresol is a biocide with widespread use in industry and pharmaceutical products. It is an occasional human contact sensitizer. The sensitizing potential of chlorocresol was judged strong using the guinea pig maximization test (GPMT) and doubtful in the less sensitive open epicutaneous test ...

  2. Tooth sensitivity and whitening.

    Science.gov (United States)

    Swift, Edward J

    2005-09-01

    This article presents a review of the basic concepts of tooth sensitivity and how those concepts apply to cervical dentin hypersensitivity and the sensitivity frequently associated with tooth whitening. The etiology and treatment of cervical dentin hypersensitivity are described. The clinical presentation, incidence, and predisposing factors for sensitivity associated with tooth whitening also are discussed.

  3. A discourse on sensitivity analysis for discretely-modeled structures

    Science.gov (United States)

    Adelman, Howard M.; Haftka, Raphael T.

    1991-01-01

    A descriptive review is presented of the most recent methods for performing sensitivity analysis of the structural behavior of discretely-modeled systems. The methods are generally but not exclusively aimed at finite element modeled structures. Topics included are: selections of finite difference step sizes; special consideration for finite difference sensitivity of iteratively-solved response problems; first and second derivatives of static structural response; sensitivity of stresses; nonlinear static response sensitivity; eigenvalue and eigenvector sensitivities for both distinct and repeated eigenvalues; and sensitivity of transient response for both linear and nonlinear structural response.

  4. Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression

    Directory of Open Access Journals (Sweden)

    Brandon H. Cline

    2015-02-01

    Full Text Available Central insulin receptor-mediated signalling is attracting the growing attention of researchers because of rapidly accumulating evidence implicating it in the mechanisms of plasticity, stress response and neuropsychiatric disorders including depression. Dicholine succinate (DS, a mitochondrial complex II substrate, was shown to enhance insulin-receptor mediated signaling in neurons and is regarded as a sensitizer of the neuronal insulin receptor. Compounds enhancing neuronal insulin receptor-mediated transmission exert an antidepressant-like effect in several pre-clinical paradigms of depression; similarly, such properties for DS were found with a stress-induced anhedonia model. Here, we additionally studied the effects of DS on several variables which were ameliorated by other insulin receptor sensitizers in mice. Pre-treatment with DS of chronically stressed C57BL6 mice rescued normal contextual fear conditioning, hippocampal gene expression of NMDA receptor subunit NR2A, the NR2A/NR2B ratio and increased REM sleep rebound after acute predation. In 18-month-old C57BL6 mice, a model of elderly depression, DS restored normal sucrose preference and activated the expression of neural plasticity factors in the hippocampus as shown by Illumina microarray. Finally, young naïve DS-treated C57BL6 mice had reduced depressive- and anxiety-like behaviours and, similarly to imipramine-treated mice, preserved hippocampal levels of the phosphorylated (inactive form of GSK3 beta that was lowered by forced swimming in pharmacologically naïve animals. Thus, DS can ameliorate behavioural and molecular outcomes under a variety of stress- and depression-related conditions. This further highlights neuronal insulin signalling as a new factor of pathogenesis and a potential pharmacotherapy of affective pathologies.

  5. Varroa Sensitive Hygiene and Drone Brood

    Science.gov (United States)

    Honey bees have been bred to express high levels of varroa sensitive hygiene (VSH), which is the removal of mite-infested pupae from capped worker brood. This hygienic behavior is a complex interaction of bees and brood in which brood cells sometimes are inspected, and then brood is either removed (...

  6. Mechanisms of metabonomic for a gateway drug: nicotine priming enhances behavioral response to cocaine with modification in energy metabolism and neurotransmitter level.

    Science.gov (United States)

    Li, Hongyu; Bu, Qian; Chen, Bo; Shao, Xue; Hu, Zhengtao; Deng, Pengchi; Lv, Lei; Deng, Yi; Zhu, Ruiming; Li, Yan; Zhang, Baolai; Hou, Jing; Du, Changman; Zhao, Qian; Fu, Dengqi; Zhao, Yinglan; Cen, Xiaobo

    2014-01-01

    Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP) models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. (1)H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc) and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

  7. Mechanisms of metabonomic for a gateway drug: nicotine priming enhances behavioral response to cocaine with modification in energy metabolism and neurotransmitter level.

    Directory of Open Access Journals (Sweden)

    Hongyu Li

    Full Text Available Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. (1H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

  8. Behavioral coaching.

    Science.gov (United States)

    Seniuk, Holly A; Witts, Benjamin N; Williams, W Larry; Ghezzi, Patrick M

    2013-01-01

    The term behavioral coaching has been used inconsistently in and outside the field of behavior analysis. In the sports literature, the term has been used to describe various intervention strategies, and in the organizational behavior management literature it has been used to describe an approach to training management personnel and staff. This inconsistency is problematic in terms of the replication of behavioral coaching across studies and aligning with Baer, Wolf, and Risley's (1968) technological dimension of applied behavior analysis. The current paper will outline and critique the discrepancies in the use of the term and suggest how Martin and Hrycaiko's (1983) characteristics of behavioral coaching in sports may be used to bring us closer to establishing a consistent definition of the term. In addition, we will suggest how these characteristics can also be applicable to the use of the term behavioral coaching in other domains of behavior analysis.

  9. Verbal behavior

    OpenAIRE

    Michael, Jack

    1984-01-01

    The recent history and current status of the area of verbal behavior are considered in terms of three major thematic lines: the operant conditioning of adult verbal behavior, learning to be an effective speaker and listener, and developments directly related to Skinner's Verbal Behavior. Other topics not directly related to the main themes are also considered: the work of Kurt Salzinger, ape-language research, and human operant research related to rule-governed behavior.

  10. Verbal behavior

    OpenAIRE

    Michael, Jack

    1984-01-01

    The recent history and current status of the area of verbal behavior are considered in terms of three major thematic lines: the operant conditioning of adult verbal behavior, learning to be an effective speaker and listener, and developments directly related to Skinner's Verbal Behavior. Other topics not directly related to the main themes are also considered: the work of Kurt Salzinger, ape-language research, and human operant research related to rule-governed behavior.

  11. Sensitivity and uncertainty analysis

    CERN Document Server

    Cacuci, Dan G; Navon, Ionel Michael

    2005-01-01

    As computer-assisted modeling and analysis of physical processes have continued to grow and diversify, sensitivity and uncertainty analyses have become indispensable scientific tools. Sensitivity and Uncertainty Analysis. Volume I: Theory focused on the mathematical underpinnings of two important methods for such analyses: the Adjoint Sensitivity Analysis Procedure and the Global Adjoint Sensitivity Analysis Procedure. This volume concentrates on the practical aspects of performing these analyses for large-scale systems. The applications addressed include two-phase flow problems, a radiative c

  12. Allergic sensitization: screening methods

    DEFF Research Database (Denmark)

    Ladics, Gregory S.; Fry, Jeremy; Goodman, Richard

    2014-01-01

    Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus...... of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing...

  13. Periodic behaviors

    CERN Document Server

    Napp, Diego; Shankar, Shiva

    2010-01-01

    This paper studies behaviors that are defined on a torus, or equivalently, behaviors defined in spaces of periodic functions, and establishes their basic properties analogous to classical results of Malgrange, Palamodov, Oberst et al. for behaviors on R^n. These properties - in particular the Nullstellensatz describing the Willems closure - are closely related to integral and rational points on affine algebraic varieties.

  14. PERIODIC BEHAVIORS

    NARCIS (Netherlands)

    Napp, Diego; Put, Marius van der; Shankar, Shiva

    2010-01-01

    This paper studies behaviors that are defined on a torus, or equivalently, behaviors defined in spaces of periodic functions, and establishes their basic properties analogous to classical results of Malgrange, Palamodov, Oberst et al. for behaviors on R(n). These properties-in particular the Nullste

  15. Behaviorally Speaking.

    Science.gov (United States)

    Porter, Elias H.; Dutton, Darell W. J.

    1987-01-01

    Consists of two articles focusing on (1) a modern behavioral model that takes cues from Hippocrates' Four Temperaments and (2) use of a behavioral approach to improve the effectiveness of meetings. Lists positive and negative behaviors within the meeting context. (CH)

  16. The importance of dye chemistry and TiCl4 surface treatment in the behavior of Al2O3 recombination barrier layers deposited by atomic layer deposition in solid-state dye-sensitized solar cells

    KAUST Repository

    Brennan, Thomas P.

    2012-01-01

    Atomic layer deposition (ALD) was used to fabricate Al 2O 3 recombination barriers in solid-state dye-sensitized solar cells (ss-DSSCs) employing an organic hole transport material (HTM) for the first time. Al 2O 3 recombination barriers of varying thickness were incorporated into efficient ss-DSSCs utilizing the Z907 dye adsorbed onto a 2 μm-thick nanoporous TiO 2 active layer and the HTM spiro-OMeTAD. The impact of Al 2O 3 barriers was also studied in devices employing different dyes, with increased active layer thicknesses, and with substrates that did not undergo the TiCl 4 surface treatment. In all instances, electron lifetimes (as determined by transient photovoltage measurements) increased and dark current was suppressed after Al 2O 3 deposition. However, only when the TiCl 4 treatment was eliminated did device efficiency increase; in all other instances efficiency decreased due to a drop in short-circuit current. These results are attributed in the former case to the similar effects of Al 2O 3 ALD and the TiCl 4 surface treatment whereas the insulating properties of Al 2O 3 hinder charge injection and lead to current loss in TiCl 4-treated devices. The impact of Al 2O 3 barrier layers was unaffected by doubling the active layer thickness or using an alternative ruthenium dye, but a metal-free donor-π-acceptor dye exhibited a much smaller decrease in current due to its higher excited state energy. We develop a model employing prior research on Al 2O 3 growth and dye kinetics that successfully predicts the reduction in device current as a function of ALD cycles and is extendable to different dye-barrier systems. © This journal is the Owner Societies 2012.

  17. Drug Diffusion Behavior of pH-Sensitive PMAA-co-poloxamer Hydrogels%药物在pH敏感聚甲基丙烯酸-poloxamer水凝胶中的扩散行为

    Institute of Scientific and Technical Information of China (English)

    徐晖; 丁平田; 赵会英; 郑俊民

    2001-01-01

    The pH-sensitive hydrogel networks comprising of MAA and poloxamer were synthesizedby free-radical solution polymerization. The gels exhibit pH-dependant solute diffusivity due to theformation or disruption of hydrogen bondings between MAA and EO unit in poloxamer molecules.The values of diffusion coefficients of dextromethorphan (DMP) and vitamin (Vb12) were found inrange from 10-7 to 10-6 cm2/s in uncomplexed hydrogels (pH 7.0) and from 10-11 to 10-8 cm2/s incomplexed hydrogels(pH 4.0) ,respectively. Solute diffusivity decreased as solute size increased. Themole ratio of EO unit to MAA unit is the main factor that affects equilibrium swelling, solute partitionand permeability characteristics of these hydrogels.%采用自由基溶液聚合方法制备甲基丙烯酸(MAA)和poloxamer的共聚物水凝胶,研究药物在此水凝胶中的扩散行为.由于MAA与poloxamer中乙氧基(EO)的氢键络合作用,水凝胶的溶胀和水凝胶中药物的扩散具有pH敏感性,络合状态水凝胶(pH为4.0)中氢溴酸右美沙芬和维生素B12的扩散系数在10-11~10-8 cm2/s之间,溶胀状态时(pH为7.0)为10-7~10-6cm2/s.EO与MAA的摩尔比是影响水凝胶平衡溶胀和药物在水凝胶中的分配与扩散性质的重要因素.

  18. A pH-sensitive Modified Polyacrylamide Hydrogel

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A pH-sensitive modified polyacrylamide hydrogel was prepared by two steps and the modified polyacrylamide was characterized by 1HNMR spectrum. The surface morphology and swelling behavior of the hydrogels were investigated.

  19. 高开孔率染料敏化太阳能电池一体化模块及其性能优化%Monolithic Module Design and Behavior Improvement of Large Area Dye-sensitized Solar Cell

    Institute of Scientific and Technical Information of China (English)

    马辉; 刘志勇; 鲁玉明; 金晓艳; 蔡传兵

    2011-01-01

    A new type of simple and monolithic large size dye-sensitized solar cell (DSC) module was designed with 85% aperture ratio (ratio of active area to total area), which was much higher than that of traditional series and parallel modules. The present module reduces the transfer resistance through the electroplated nickel grid on F-doped SnO2 (FTO) of anode as well as the nickel film on the FTO of counter electrode. The nickel grid and film are inside the cell and the separation of the cell is not required, which is useful to reduce the block part of light and beneficial to improve the harvest of light energy. The photoelectric conversion efficiency (n) with the active area of 510 mm2 reaches 3.00% (AM 1.5, 100 mW/cm2) and the fill factor (FF) is 0.594, meanwhile the rj and FF of DSC without nickel layer modification is only 0.537% and 0.251. So it is obvious that this novel designed module is very effective in the performance improvement. The underlying mechanism is understood based on the measurement of the electrochemical impedance spectroscopy (EIS) as well as the quality check of nickel film by scanning electron microscopy (SEM) and X-ray diffraction (XRD).%本实验设计了一种简单有效的一体化大尺度染料敏化太阳能电池(DSC)模块,开孔率(有效面积与总面积之比)高达85%,远高于传统的串联和并联模块设计.该设计采用在光阳极导电玻璃表面电镀镍栅极和对电极导电玻璃表面电镀镍薄膜修饰来降低电池传输电阻.有效面积为510 mm2的电池模块光电转换效率η达到3.00%(AM l.5,1 00 mW/cm2),填充因子(FF)为0.594,与未镀镍的样品(η为0.537%,FF为0.251)相比,性能显著提高.并利用阻抗谱对大面积性能改善进行了解释,还利用SEM、XRD等分析了电镀镍薄膜的质量.

  20. Are Psychopaths Morally Sensitive?

    Science.gov (United States)

    Maxwell, Bruce; Le Sage, Leonie

    2009-01-01

    Philosophical and psychological opinion is divided over whether moral sensitivity, understood as the ability to pick out a situation's morally salient features, necessarily involves emotional engagement. This paper seeks to offer insight into this question. It reasons that if moral sensitivity does draw significantly on affective capacities of…

  1. Tuned cavity magnetometer sensitivity.

    Energy Technology Data Exchange (ETDEWEB)

    Okandan, Murat; Schwindt, Peter

    2009-09-01

    We have developed a high sensitivity (sensitivity levels.

  2. Assessing Sensitiveness to Transport

    DEFF Research Database (Denmark)

    Lieb, Christoph; Suter, Stefan; Sánchez, Alfredo

    Summary The EU-project ASSET (ASessing SEnsitiveness to Transport) aims at developing and implementing a concise concept to assess transport sensitive areas (TSA) in a European context, i.e. areas in which transport leads to more serious impacts than in other areas. The aim of work package 2 (WP2...

  3. Structure sensitivity in adsorption

    DEFF Research Database (Denmark)

    Hammer, Bjørk; Nielsen, Ole Holm; Nørskov, Jens Kehlet

    1997-01-01

    The structure sensitivity of CO adsorption on different flat, stepped, kinked and reconstructed Pt surfaces is studied using large-scale density-functional calculations. We find an extremely strong structure sensitivity in the adsorption energy with variations up to 1 eV (or 100%) from one...

  4. Mixed sensitivity design

    NARCIS (Netherlands)

    Kwakernaak, Huibert; Camacho, E.F.; Basanez, L.; Puente, de la J.A.

    2002-01-01

    Mixed sensitivity design of a linear multivariable control system amounts toshaping its sensitivity functions to achieve the design targets of closed-loop system performance and robustness. Both H∞ and H2 optimization may be used to this end. Various tools are available, in particular low and high f

  5. Making Behavioral Activation More Behavioral

    Science.gov (United States)

    Kanter, Jonathan W.; Manos, Rachel C.; Busch, Andrew M.; Rusch, Laura C.

    2008-01-01

    Behavioral Activation, an efficacious treatment for depression, presents a behavioral theory of depression--emphasizing the need for clients to contact positive reinforcement--and a set of therapeutic techniques--emphasizing provision of instructions rather than therapeutic provision of reinforcement. An integration of Behavioral Activation with…

  6. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  7. Behavior to the fracture of an AISI 304 stainless steel sensitized in BWR reactor conditions (288 degrees Centigrade and 80 Kg/cm{sup 2}); Comportamiento a la fractura de un acero inoxidable AISI 304 sensibilizado en condiciones de reactor BWR (288 grados Centigrados y 80 Kg/cm{sup 2})

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez C, R.; Diaz S, A.; Garcia R, R.; Aguilar T, A.; Gachuz M, M.; Arganis J, C.; Merino C, J. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1999-07-01

    It is a knew fact that ductility of a lot of structural alloys can be deteriorated by the environment effect which are exposed, and that their consequent embrittlement can put in doubt the safety of their functioning; such is the case of austenitic stainless steels used in internal components of the BWR type reactors which not only is subjected to the effect combined of the aggressive environment which surround it (pressure, temperature, corrosion potential, conductivity medium, local state of efforts, etc.), but also to the action of present neutron radiation, manifesting microstructural changes which are reflected in the augmentation of its susceptibility to the intergranular cracking, phenomena generally known as IASCC ''Irradiation Assisted Stress Corrosion Cracking''. Once appeared the cracking in the material, the useful life of a component is limited by the rapidity to growth of these cracking, making necessary evaluations which can to predict its behavior, therefore the present work shows the preliminary results for determining the behavior to the fracture of an AISI 304 stainless steel sensitized, in a dynamic recirculation circuit which allows to simulate the operation conditions of a BWR reactor (288 Centigrade and 80 kg/cm{sup 2}). (Author)

  8. Psychological behaviorism and behaviorizing psychology

    Science.gov (United States)

    Staats, Arthur W.

    1994-01-01

    Paradigmatic or psychological behaviorism (PB), in a four-decade history of development, has been shaped by its goal, the establishment of a behaviorism that can also serve as the approach in psychology (Watson's original goal). In the process, PB has become a new generation of behaviorism with abundant heuristic avenues for development in theory, philosophy, methodology, and research. Psychology has resources, purview and problem areas, and nascent developments of many kinds, gathered in chaotic diversity, needing unification (and other things) that cognitivism cannot provide. Behaviorism can, within PB's multilevel framework for connecting and advancing both psychology and behaviorism. PMID:22478175

  9. Psychological behaviorism and behaviorizing psychology.

    Science.gov (United States)

    Staats, A W

    1994-01-01

    Paradigmatic or psychological behaviorism (PB), in a four-decade history of development, has been shaped by its goal, the establishment of a behaviorism that can also serve as the approach in psychology (Watson's original goal). In the process, PB has become a new generation of behaviorism with abundant heuristic avenues for development in theory, philosophy, methodology, and research. Psychology has resources, purview and problem areas, and nascent developments of many kinds, gathered in chaotic diversity, needing unification (and other things) that cognitivism cannot provide. Behaviorism can, within PB's multilevel framework for connecting and advancing both psychology and behaviorism.

  10. Generating Nonverbal Signals for a Sensitive Artificial Listener

    NARCIS (Netherlands)

    Heylen, Dirk K.J.; Nijholt, Antinus; Poel, Mannes; Esposito, A.; Faunder-Zanny, M.; Keller, E.; Marinaro, M.

    2007-01-01

    In the Sensitive Artificial Listener project research is performed with the aim to design an embodied agent that not only generates the appropriate nonverbal behaviors that accompany speech, but that also displays verbal and nonverbal behaviors during the production of speech by its conversational

  11. Scopolamine prevents the development of sensitization to morphine

    Institute of Scientific and Technical Information of China (English)

    Gujun; Zhouwen-hua; Yangguo-dong

    2004-01-01

    AIM : The repeated use of opiates in humans has been associated with progressive enhancement of anxiety, panic attacks, and eventually paranoid psychosis. The appearance of such behaviors has been termed behavioral sensitization,which forms part of the basic pathological mechanisms involved in drug addiction. Muscarinic cholinergic receptors of the

  12. Teleological behaviorism.

    Science.gov (United States)

    Rachlin, H

    1992-11-01

    A psychological science of efficient causes, using internal mechanisms to explain overt behavior, is distinguished from another psychological science, based on Aristotelian final causes, using external objects and goals to explain overt behavior. Efficient-cause psychology is designed to answer the question of how a particular act is emitted; final-cause psychology is designed to answer the question of why a particular act is emitted. Physiological psychology, modern cognitive psychology, and some parts of behaviorism including Skinnerian behaviorism are efficient-cause psychologies; final-cause psychology, a development of Skinnerian behaviorism, is here called teleological behaviorism. Each of these two conceptions of causality in psychology implies a different view of the mind, hence a different meaning of mental terms.

  13. Environmental contaminants as origins of disordered behavior

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, B.

    1978-01-01

    Behavioral toxicology studies the behavioral effects of contaminants, such as heavy metals, in environmental and occupational settings. A classic example of metal poisoning with behavioral effects is Pink Disease, or acrodynia, due to mercurous chloride intoxication in children. Thalidomide is a more prominent example. Behavioral changes, unlike tangible consequences of pollution, are difficult to perceive as dangers and to correct. Other examples of environmental pollutants causing behavioral symptoms upon intoxication are polybrominated biphenyls, lead, mercury, methylmercury, and a variety of food additives. Sensitivity to food colors and flavors is suspected to be the cause of behavioral abnormalities in children now labeled as hyperactive or hyperkinetic. (ERB)

  14. Spontaneous baroreflex sensitivity

    DEFF Research Database (Denmark)

    Barthel, Petra; Bauer, Axel; Müller, Alexander;

    2012-01-01

    Low baroreflex sensitivity (BRS) indicates poor prognosis after acute myocardial infarction. Noninvasive BRS assessment is complicated by nonstationarities and noise in electrocardiogram and pressure signals. Phase-rectified signal averaging is a novel signal processing technology overcoming...

  15. Developing cultural sensitivity

    DEFF Research Database (Denmark)

    Ruddock, Heidi; Turner, deSalle

    2007-01-01

    . Background. Many countries are becoming culturally diverse, but healthcare systems and nursing education often remain mono-cultural and focused on the norms and needs of the majority culture. To meet the needs of all members of multicultural societies, nurses need to develop cultural sensitivity......Title. Developing cultural sensitivity: nursing students’ experiences of a study abroad programme Aim. This paper is a report of a study to explore whether having an international learning experience as part of a nursing education programme promoted cultural sensitivity in nursing students...... and incorporate this into caregiving. Method. A Gadamerian hermeneutic phenomenological approach was adopted. Data were collected in 2004 by using in-depth conversational interviews and analysed using the Turner method. Findings. Developing cultural sensitivity involves a complex interplay between becoming...

  16. Cobalt sensitization and dermatitis

    DEFF Research Database (Denmark)

    Thyssen, Jacob P

    2012-01-01

    : This clinical review article presents clinical and scientific data on cobalt sensitization and dermatitis. It is concluded that cobalt despite being a strong sensitizer and a prevalent contact allergen to come up on patch testing should be regarded as a very complex metal to test with. Exposure...... data together with clinical data from metal workers heavily exposed to cobalt suggest that patch-test reactions are sometimes false positive and that patch testers should carefully evaluate their clinical relevance....

  17. Charge-sensitive amplifier

    Directory of Open Access Journals (Sweden)

    Startsev V. I.

    2008-02-01

    Full Text Available The authors consider design and circuit design techniques of reduction of the influence of the pyroelectric effect on operation of the charge sensitive amplifiers. The presented experimental results confirm the validity of the measures taken to reduce the impact of pyroelectric currents. Pyroelectric currents are caused by the influence of the temperature gradient on the piezoelectric sensor and on the output voltage of charge sensitive amplifiers.

  18. Octopaminergic modulation of contrast sensitivity

    Directory of Open Access Journals (Sweden)

    Roel ede Haan

    2012-08-01

    Full Text Available Sensory systems adapt to prolonged stimulation by decreasing their response to prevailing stimulus conditions. Whereas visual motion adaptation has traditionally been studied in immobilized animals, recent work indicates that the animal’s behavioral state influences the response properties of higher-order motion vision-sensitive neurons. During insect flight octopamine is released, and pharmacological octopaminergic activation can induce a fictive locomotor state. In the insect optic ganglia, lobula plate tangential cells (LPTCs spatially pool input from local elementary motion detectors (EMDs that correlate luminosity changes from two spatially discrete inputs after delaying the signal from one. The LPTC velocity optimum thereby depends on the spatial separation of the inputs and on the EMD’s delay properties. Recently it was shown that behavioral activity increases the LPTC velocity optimum, with modeling suggesting this to originate in the EMD’s temporal delay filters. However, behavior induces an additional post-EMD effect: the LPTC membrane conductance increases in flying flies. To physiologically investigate the degree to which activity causes presynaptic and postsynaptic effects, we conducted intracellular recordings of Eristalis horizontal system neurons. We constructed contrast response functions before and after adaptation at different temporal frequencies, with and without the octopamine receptor agonist chlordimeform (CDM. We extracted three motion adaptation components, where two are likely generated presynaptically of the LPTCs, and one within them. We found that CDM affected the early, EMD associated contrast gain reduction, temporal frequency dependently. However, a CDM-induced change of the HS membrane conductance disappeared during and after visual stimulation. This suggests that physical activity mainly affects motion adaptation presynaptically of LPTCs, whereas post-EMD effects have a minimal effect.

  19. Behavioral economics.

    Science.gov (United States)

    Camerer, Colin F

    2014-09-22

    Behavioral economics uses evidence from psychology and other social sciences to create a precise and fruitful alternative to traditional economic theories, which are based on optimization. Behavioral economics may interest some biologists, as it shifts the basis for theories of economic choice away from logical calculation and maximization and toward biologically plausible mechanisms.

  20. Aggressive behavior

    NARCIS (Netherlands)

    Didden, H.C.M.; Lindsay, W.R.; Lang, R.; Sigafoos, J.; Deb, S.; Wiersma, J.; Peters-Scheffer, N.C.; Marschik, P.B.; O’Reilly, M.F.; Lancioni, G.E.

    2016-01-01

    Aggressive behavior is common in individuals with intellectual and developmental disabilities (IDDs), and it is most often targeted for intervention. Psychological, contextual, and biological risk factors may contribute to the risk of aggressive behavior. Risk factors are gender (males), level of ID

  1. Aggressive behavior

    NARCIS (Netherlands)

    Didden, H.C.M.; Lindsay, W.R.; Lang, R.; Sigafoos, J.; Deb, S.; Wiersma, J.; Peters-Scheffer, N.C.; Marschik, P.B.; O’Reilly, M.F.; Lancioni, G.E.

    2016-01-01

    Aggressive behavior is common in individuals with intellectual and developmental disabilities (IDDs), and it is most often targeted for intervention. Psychological, contextual, and biological risk factors may contribute to the risk of aggressive behavior. Risk factors are gender (males), level of ID

  2. Precursor manic behavior in the assessment and treatment of episodic problem behavior for a woman with a dual diagnosis.

    Science.gov (United States)

    Allen, Marissa B; Baker, Jonathan C; Nuernberger, Jodi E; Vargo, Kristina K

    2013-01-01

    A functional analysis examined the relation between consequences that maintained episodic problem behavior (aggression, property destruction, and elopement) in the presence and absence of manic behaviors (MB). Results suggested that the presence of MB was correlated with the sensitivity of problem behavior to attention as a reinforcer during a functional analysis and that problem behaviors were maintained by attention. Noncontingent reinforcement was subsequently implemented and demonstrated to be effective in reducing problem behavior during the presence of manic behaviors.

  3. Optimally matching support and perceived spousal sensitivity.

    Science.gov (United States)

    Cutrona, Carolyn E; Shaffer, Philip A; Wesner, Kristin A; Gardner, Kelli A

    2007-12-01

    Partner sensitivity is an important antecedent of both intimacy (H. T. Reis & P. Shaver, 1988) and attachment (M. D. S. Ainsworth, 1989). On the basis of the optimal matching model of social support (C. E. Cutrona & D. Russell, 1990), support behaviors that "matched" the support goals of the stressed individual were predicted to lead to the perception of partner sensitivity. Predictions were tested with 59 married couples, who engaged in a videotaped self-disclosure task. Matching support was defined as the disclosure of emotions followed by emotional support or a request for information followed by informational support. Partial evidence was found for the predictions. Matching support following the disclosure of emotions was predictive of perceived partner sensitivity. Mismatched support following the disclosure of emotions predicted lower marital satisfaction, through the mediation of partner sensitivity. Matching support following a request for information was not predictive of perceived partner sensitivity, but negative partner responses (e.g., criticism or sarcasm) following a request for information negatively predicted perceptions of partner sensitivity. The importance of considering the context of support transactions is discussed.

  4. Reduced taste sensitivity in congenital blindness

    DEFF Research Database (Denmark)

    Gagnon, Lea; Kupers, Ron; Ptito, Maurice

    2013-01-01

    Sight is undoubtedly not only important for food identification and selection but also for the modulation of gustatory sensitivity. We can, therefore, assume that taste sensitivity and eating habits are affected by visual deprivation from birth. We measured taste detection and identification...... behavioral results showed that compared with the normal sighted, blind subjects have increased thresholds for taste detection and taste identification. This finding is at odds with the superior performance of congenitally blind subjects in several tactile, auditory and olfactory tasks. Our psychometric data...... further indicate that blind subjects more strongly rely on internal hunger and satiety cues, instead of external contextual or emotional cues, to decide when and what to eat. We suggest that the lower taste sensitivity observed in congenitally blind individuals is due to various blindness...

  5. Sensitizing properties of proteins

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Ladics, Gregory S; McClain, Scott

    2014-01-01

    The scope of allergy risk is diverse considering the myriad ways in which protein allergenicity is affected by physiochemical characteristics of proteins. The complexity created by the matrices of foods and the variability of the human immune system add additional challenges to understanding...... the relationship between sensitization potential and allergy disease. To address these and other issues, an April 2012 international symposium was held in Prague, Czech Republic, to review and discuss the state-of-the-science of sensitizing properties of protein allergens. The symposium, organized by the Protein...... Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute, featured presentations on current methods, test systems, research trends, and unanswered questions in the field of protein sensitization. A diverse group of over 70 interdisciplinary...

  6. Cost Behavior

    DEFF Research Database (Denmark)

    Hoffmann, Kira

    The objective of this dissertation is to investigate determinants and consequences of asymmetric cost behavior. Asymmetric cost behavior arises if the change in costs is different for increases in activity compared to equivalent decreases in activity. In this case, costs are termed “sticky......” if the change is less when activity falls than when activity rises, whereas costs are termed “anti-sticky” if the change is more when activity falls than when activity rises. Understanding such cost behavior is especially relevant for decision-makers and financial analysts that rely on accurate cost information...

  7. Behavioral epigenetics

    Science.gov (United States)

    Lester, Barry M.; Tronick, Edward; Nestler, Eric; Abel, Ted; Kosofsky, Barry; Kuzawa, Christopher W.; Marsit, Carmen J.; Maze, Ian; Meaney, Michael J.; Monteggia, Lisa M.; Reul, Johannes M. H. M.; Skuse, David H.; Sweatt, J. David; Wood, Marcelo A.

    2013-01-01

    Sponsored by the New York Academy of Sciences, the Warren Alpert Medical School of Brown University and the University of Massachusetts Boston, “Behavioral Epigenetics” was held on October 29–30, 2010 at the University of Massachusetts Boston Campus Center, Boston, Massachusetts. This meeting featured speakers and panel discussions exploring the emerging field of behavioral epigenetics, from basic biochemical and cellular mechanisms to the epigenetic modulation of normative development, developmental disorders, and psychopathology. This report provides an overview of the research presented by leading scientists and lively discussion about the future of investigation at the behavioral epigenetic level. PMID:21615751

  8. Cost Behavior

    DEFF Research Database (Denmark)

    Hoffmann, Kira

    The objective of this dissertation is to investigate determinants and consequences of asymmetric cost behavior. Asymmetric cost behavior arises if the change in costs is different for increases in activity compared to equivalent decreases in activity. In this case, costs are termed “sticky......” if the change is less when activity falls than when activity rises, whereas costs are termed “anti-sticky” if the change is more when activity falls than when activity rises. Understanding such cost behavior is especially relevant for decision-makers and financial analysts that rely on accurate cost information...

  9. Highly Sensitive Optical Receivers

    CERN Document Server

    Schneider, Kerstin

    2006-01-01

    Highly Sensitive Optical Receivers primarily treats the circuit design of optical receivers with external photodiodes. Continuous-mode and burst-mode receivers are compared. The monograph first summarizes the basics of III/V photodetectors, transistor and noise models, bit-error rate, sensitivity and analog circuit design, thus enabling readers to understand the circuits described in the main part of the book. In order to cover the topic comprehensively, detailed descriptions of receivers for optical data communication in general and, in particular, optical burst-mode receivers in deep-sub-µm CMOS are presented. Numerous detailed and elaborate illustrations facilitate better understanding.

  10. Sensitivity analysis of SPURR

    Energy Technology Data Exchange (ETDEWEB)

    Witholder, R.E.

    1980-04-01

    The Solar Energy Research Institute has conducted a limited sensitivity analysis on a System for Projecting the Utilization of Renewable Resources (SPURR). The study utilized the Domestic Policy Review scenario for SPURR agricultural and industrial process heat and utility market sectors. This sensitivity analysis determines whether variations in solar system capital cost, operation and maintenance cost, and fuel cost (biomass only) correlate with intuitive expectations. The results of this effort contribute to a much larger issue: validation of SPURR. Such a study has practical applications for engineering improvements in solar technologies and is useful as a planning tool in the R and D allocation process.

  11. Innate intersubjectivity: newborns' sensitivity to communication disturbance.

    Science.gov (United States)

    Nagy, Emese

    2008-11-01

    In most of our social life we communicate and relate to others. Successful interpersonal relating is crucial to physical and mental well-being and growth. This study, using the still-face paradigm, demonstrates that even human neonates (n = 90, 3-96 hr after birth) adjust their behavior according to the social responsiveness of their interaction partner. If the interaction partner becomes unresponsive, newborns will also change their behavior, decrease eye contact, and display signs of distress. Even after the interaction partner resumes responsiveness, the effects of the communication disturbance persist as a spillover. These results indicate that even newborn infants sensitively monitor the behavior of others and react as if they had innate expectations regarding rules of interpersonal interaction.

  12. Pain threshold - measure of pain sensitivity or social behavior?

    Directory of Open Access Journals (Sweden)

    Modić-Stanke Koraljka

    2016-01-01

    Full Text Available The aim was to examine the effect of the experimenter’s social status and its interaction with participant’s gender on pressure pain threshold. Both male and female students participated in the study (N = 96 and were evenly assigned into two groups which differed only in the professional status of the experimenter who was a professor (higher status in one group and a student (lower status in the other. The factorial ANOVA revealed statistically significant and large main effects of the experimenter’s status and the participants’ gender, indicating higher pain thresholds in male participants and in the higher status experimenter group. Although both males and females had higher pain thresholds when measured by a higher status experimenter, a statistically significant interaction revealed that status affected male participants more so than females. The obtained results are probably due to social behaviour, emphasizing relevance of the experimenter’s and participants’ characteristics in pain measurement.

  13. Sensitivity analysis of the seakeeping behavior of trimaran ships

    OpenAIRE

    KURULTAY, Aziz Alper

    2003-01-01

    Approved for public release; distribution is unlimited The dynamic response of the ship while operating in different sea conditions is one of the design parameters of a hull form. The objective of this thesis is to analyze the seakeeping response of trimaran hulls. A three-dimensional Rankine source panel method is used to achieve that. Seakeeping response characteristics of a typical trimaran with a variable separation ratio (the ratio of the lateral distance between center hull and s...

  14. Reward sensitivity and food addiction in women.

    Science.gov (United States)

    Loxton, Natalie J; Tipman, Renée J

    2016-10-15

    Sensitivity to the rewarding properties of appetitive substances has long been implicated in excessive consumption of palatable foods and drugs of abuse. Previous research focusing on individual differences in reward responsiveness has found heightened trait reward sensitivity to be associated with binge-eating, hazardous drinking, and illicit substance use. Food addiction has been proposed as an extreme form of compulsive-overeating and has been associated with genetic markers of heightened reward responsiveness. However, little research has explicitly examined the association between reward sensitivity and food addiction. Further, the processes by which individual differences in this trait are associated with excessive over-consumption has not been determined. A total of 374 women from the community completed an online questionnaire assessing reward sensitivity, food addiction, emotional, externally-driven, and hedonic eating. High reward sensitivity was significantly associated with greater food addiction symptoms (r = 0.31). Bootstrapped tests of indirect effects found the relationship between reward sensitivity and food addiction symptom count to be uniquely mediated by binge-eating, emotional eating, and hedonic eating (notably, food availability). These indirect effects held even when controlling for BMI, anxiety, depression, and trait impulsivity. This study further supports the argument that high levels of reward sensitivity may offer a trait marker of vulnerability to excessive over-eating, beyond negative affect and impulse-control deficits. That the hedonic properties of food (especially food availability), emotional, and binge-eating behavior act as unique mediators suggest that interventions for reward-sensitive women presenting with food addiction may benefit from targeting food availability in addition to management of negative affect.

  15. Behaviorally inadequate

    DEFF Research Database (Denmark)

    Kasperbauer, Tyler Joshua

    2014-01-01

    is to reject or at least minimize the requirement that environmental ethics must provide protection and assistance to the environment. Virtue theory is often favored by environmentalists precisely because it does matter what one's reasons are for acting, even if one's actions are ineffective at producing......According to situationism in psychology, behavior is primarily influenced by external situational factors rather than internal traits or motivations such as virtues. Environmental ethicists wish to promote pro-environmental behaviors capable of providing adequate protection for the environment......, but situationist critiques suggest that character traits, and environmental virtues, are not as behaviorally robust as is typically supposed. Their views present a dilemma. Because ethicists cannot rely on virtues to produce pro-environmental behaviors, the only real way of salvaging environmental virtue theory...

  16. Behavioral finance

    Directory of Open Access Journals (Sweden)

    Kapor Predrag

    2014-01-01

    Full Text Available This paper discuss some general principles of behavioral finance Behavioral finance is the dynamic and promising field of research that mergers concepts from financial economics and cognitive psychology in attempt to better understand systematic biases in decision-making process of financial agents. While the standard academic finance emphasizes theories such as modern portfolio theory and the efficient market hypothesis, the behavioral finance investigates the psychological and sociological issues that impact the decision-making process of individuals, groups and organizations. Most of the research behind behavioral finance has been empirical in nature, concentrating on what people do and why. The research has shown that people do not always act rationally, nor they fully utilise all information available to them.

  17. Behavioral epigenetics

    OpenAIRE

    Lester, Barry M.; Tronick, Edward; Nestler, Eric; Abel, Ted; Kosofsky, Barry; Kuzawa, Christopher W.; Marsit, Carmen J; Maze, Ian; Meaney, Michael J.; Monteggia, Lisa M.; Reul, Johannes M. H. M.; Skuse, David H.; Sweatt, J. David; Wood, Marcelo A.

    2011-01-01

    Sponsored by the New York Academy of Sciences, the Warren Alpert Medical School of Brown University and the University of Massachusetts Boston, “Behavioral Epigenetics” was held on October 29–30, 2010 at the University of Massachusetts Boston Campus Center, Boston, Massachusetts. This meeting featured speakers and panel discussions exploring the emerging field of behavioral epigenetics, from basic biochemical and cellular mechanisms to the epigenetic modulation of normative development, devel...

  18. Pressure pain sensitivity

    DEFF Research Database (Denmark)

    Bergmann, Natasha; Ballegaard, Søren; Holmager, Pernille

    2013-01-01

    to induce hyperalgesia.The aim of the present study was to evaluate hyperalgesia by pressure pain sensitivity (PPS) in patients with IHD, and compare PPS to questionnaires measuring depressive symptoms, reduced psychological wellbeing, and QOL as markers of stress. Design. A cross-sectional study of 361...

  19. Sensitive hydrogen leak detector

    Science.gov (United States)

    Myneni, Ganapati Rao

    1999-01-01

    A sensitive hydrogen leak detector system using passivation of a stainless steel vacuum chamber for low hydrogen outgassing, a high compression ratio vacuum system, a getter operating at 77.5 K and a residual gas analyzer as a quantitative hydrogen sensor.

  20. UNITEC SENS-IT

    Science.gov (United States)

    The UniTec Sens-It is a small gas-sensing device that can measure volatile organic compounds (VOCs). This sensor is used to measure VOCs in applications such as urban air quality, roadside pollution, and (solid waste) landfill monitoring. This operating procedure explains what yo...

  1. Fundamental Physics Microgravity Sensitivity

    Science.gov (United States)

    Israelsson, Ulf

    1998-01-01

    An introduction followed by a brief discussion about the sensitivity to microgravity environment disturbances for some recent and planned experiments in microgravity fundamental physics will be presented. In particular, correlation between gravity disturbances and the quality of science data sets measured by the Confined Helium Experiment (CHEX) during ground testing and during the November 1997 USMP-4 flight will be described.

  2. Sexuality Sensitiv