The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
Yavin Shaham - One of the best experts on this subject based on the ideXlab platform.
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effect of Yohimbine on reinstatement of operant responding in rats is dependent on cue contingency but not food reward history
Addiction Biology, 2015Co-Authors: Yuwei Chen, Yavin Shaham, Kimberly A Fiscella, Samuel Z Bacharach, Gianluigi Tanda, Donna J CaluAbstract:Yohimbine is an alpha-2 adrenoceptor antagonist that has been used in numerous studies as a pharmacological stressor in rodents, monkeys, and humans. Recently, Yohimbine has become the most common stress manipulation in studies on reinstatement of drug and food seeking. However, the wide range of conditions under which Yohimbine promotes reward seeking is significantly greater than that of stressors like intermittent footshock. Here we addressed two fundamental questions regarding Yohimbine’s effect on reinstatement of reward seeking: (1) whether the drug’s effect on operant responding is dependent on previous reward history or cue contingency, and (2) whether Yohimbine is aversive or rewarding under conditions typically used in reinstatement studies. We also used in vivo microdialysis to determine Yohimbine’s effect on dopamine levels in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). We found that the magnitude of Yohimbine-induced (0.5, 1.0, 2.0 mg/kg) operant responding during the reinstatement tests was critically dependent on the contingency between lever-pressing and discrete tone-light cue delivery but not the previous history with food reward during training. We also found that Yohimbine (2 mg/kg) did not cause conditioned place aversion. Finally, we found that Yohimbine modestly increased dopamine levels in mPFC but not NAc. Results suggest that Yohimbine’s effects on operant responding in reinstatement studies are likely independent of the history of contingent self-administration of food or drug rewards and may not be related to the commonly assumed stress-like effects of Yohimbine.
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role of corticotropin releasing factor in the median raphe nucleus in Yohimbine induced reinstatement of alcohol seeking in rats
Addiction Biology, 2013Co-Authors: A D Le, Douglas Funk, Kathleen M Coen, Zhaoxia Li, Yavin ShahamAbstract:The pharmacological stressor Yohimbine increases ongoing alcohol self-administration and reinstates alcohol seeking in rats. This effect is attenuated by systemic injections of a corticotropin-releasing factor (CRF) antagonist. The brain sites involved in CRF's role in Yohimbine-induced alcohol taking and seeking are unknown. We report that injections of the CRF receptor antagonist d-Phe CRF into the median raphe nucleus (MRN) attenuated Yohimbine-induced reinstatement of alcohol seeking but had no effect on Yohimbine-induced increases in alcohol intake during ongoing self-administration. Results indicate an important role of MRN CRF receptors in Yohimbine-induced reinstatement of alcohol seeking but not Yohimbine-induced increases in alcohol intake.
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the crf1 receptor antagonist antalarmin attenuates Yohimbine induced increases in operant alcohol self administration and reinstatement of alcohol seeking in rats
Psychopharmacology, 2007Co-Authors: Peter W Marinelli, Douglas Funk, W Juzytsch, Stephen E Harding, Kenner C Rice, Yavin ShahamAbstract:Yohimbine is an alpha-2 adrenoreceptor antagonist that provokes stress- and anxiety-like responses in both humans and laboratory animals. In rats, Yohimbine increases operant alcohol self-administration and reinstates alcohol seeking. In this study, we assess whether these effects of Yohimbine are attenuated by systemic injections of the corticotrotropin-releasing factor 1 (CRF1) receptor antagonist antalarmin. In Exp. 1, we trained rats to lever press for alcohol solutions (12% w/v, 1 h/day) over several weeks; during training, the response requirement was increased from a fixed-ratio-1 (FR-1) to a fixed-ratio-3 (FR-3) reinforcement schedule. We then tested the effect of antalarmin (10 or 20 mg/kg) on Yohimbine (1.25 mg/kg)-induced increases in operant alcohol self-administration (FR-3 reinforcement schedule). Subsequently, we assessed the effect of antalarmin on Yohimbine-induced increases in plasma corticosterone levels in the previously self-administering rats. In Exp. 2, we trained the rats to self-administer alcohol as in Exp. 1, and after extinction of the alcohol-reinforced lever responding over 13 days, we tested antalarmin’s effect on Yohimbine-induced reinstatement of alcohol seeking. Yohimbine increased operant alcohol self-administration and reinstated alcohol seeking after extinction. These effects of Yohimbine were attenuated by antalarmin. Antalarmin injections in the absence of Yohimbine had no effect on either operant alcohol self-administration or extinction responding. Antalarmin had no effect on Yohimbine-induced corticosterone release in alcohol-experienced rats. These results suggest that extrahypothalamic CRF1 receptors are involved in the effect of Yohimbine on operant alcohol self-administration and on relapse to alcohol seeking and support the notion that CRF1 receptor antagonists should be considered in alcohol addiction treatment.
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the anxiogenic drug Yohimbine reinstates methamphetamine seeking in a rat model of drug relapse
Biological Psychiatry, 2004Co-Authors: Jack D Shepard, Jennifer M Bossert, Shirley Y Liu, Yavin ShahamAbstract:Abstract Background Brain noradrenaline is involved in footshock stress-induced reinstatement of drug seeking in a rat relapse model. We studied whether Yohimbine, an α-2 adrenoceptor antagonist that increases noradrenaline release and induces anxiety-like responses in human and nonhuman subjects, would reinstate methamphetamine seeking in rats. Methods In experiment 1, the effect of Yohimbine (1.25–2.5 mg/kg) on reinstatement was compared with that of intermittent footshock (5 min; .2–.6 mA) in rats that were trained to lever press for intravenous methamphetamine (9–11 days) and subsequently underwent 7 days of extinction training. In experiment 2, the effect of Yohimbine on reinstatement of drug seeking was determined during early (1 day) and late (21 or 51 days) withdrawal periods. On the test days, rats were first given 3-hour extinction sessions and were then tested for reinstatement induced by Yohimbine. Results In experiment 1, both Yohimbine and footshock stress reinstated methamphetamine seeking after extinction. In experiment 2, extinction responding was higher after 21 or 51 withdrawal days than after 1 withdrawal day. In contrast, no significant time-dependent changes in Yohimbine-induced reinstatement were observed. Conclusions Results indicate that Yohimbine is a potent stimulus for reinstatement of methamphetamine seeking in a rat relapse model.
Andrew J Lawrence - One of the best experts on this subject based on the ideXlab platform.
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pattern of neural activation following Yohimbine induced reinstatement of alcohol seeking in rats
European Journal of Neuroscience, 2020Co-Authors: Leigh C Walker, Hanna E Kastman, Andrew J LawrenceAbstract:Alcohol use disorders represent an extensive socioeconomic burden, yet effective treatment options are suboptimal. A major hurdle in treating alcohol use disorders is the high rate of relapse. Stress is a major factor that promotes relapse in abstinent drug users; therefore, understanding neural mechanisms that underpin the effects of stress on alcohol seeking is critical. In rodent models of stress-induced relapse, the α2 -adrenoceptor antagonist, Yohimbine, is a widely used chemical stressor to elicit reinstatement of drug/alcohol seeking. However, the exact mechanism how Yohimbine precipitates reinstatement of alcohol seeking and the pattern of neural activation associated with Yohimbine-induced reinstatement is poorly understood. Therefore, we counted Fos-protein positive nuclei across 42 brain regions in alcohol-experienced alcohol preferring rats that received either Yohimbine in the home-cage (1 mg/kg i.p.) or following Yohimbine-induced reinstatement of alcohol seeking. The number of Fos-protein positive nuclei was increased in the prefrontal cortex and extended amygdala after home-cage Yohimbine compared to naive- and vehicle-treated rats. Yohimbine-induced reinstatement increased the number of Fos-protein expressing nuclei in multiple other regions including the thalamus, hypothalamus and hippocampus. We then examined inter-regional correlations in Fos-protein expression for all 42 brain regions, which showed Fos expression was more strongly positively correlated following Yohimbine-induced reinstatement of alcohol seeking, compared to home-cage Yohimbine. These data suggest low-dose Yohimbine in a non-drug-associated context activates stress/impulsivity centres within the brain, whereas Yohimbine in the drug-associated context recruits additional brain regions to drive alcohol seeking.
Douglas Funk - One of the best experts on this subject based on the ideXlab platform.
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role of corticotropin releasing factor in the median raphe nucleus in Yohimbine induced reinstatement of alcohol seeking in rats
Addiction Biology, 2013Co-Authors: A D Le, Douglas Funk, Kathleen M Coen, Zhaoxia Li, Yavin ShahamAbstract:The pharmacological stressor Yohimbine increases ongoing alcohol self-administration and reinstates alcohol seeking in rats. This effect is attenuated by systemic injections of a corticotropin-releasing factor (CRF) antagonist. The brain sites involved in CRF's role in Yohimbine-induced alcohol taking and seeking are unknown. We report that injections of the CRF receptor antagonist d-Phe CRF into the median raphe nucleus (MRN) attenuated Yohimbine-induced reinstatement of alcohol seeking but had no effect on Yohimbine-induced increases in alcohol intake during ongoing self-administration. Results indicate an important role of MRN CRF receptors in Yohimbine-induced reinstatement of alcohol seeking but not Yohimbine-induced increases in alcohol intake.
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the role of noradrenaline and 5 hydroxytryptamine in Yohimbine induced increases in alcohol seeking in rats
Psychopharmacology, 2009Co-Authors: Douglas Funk, W Juzytsch, Stephen E Harding, Paul J FletcherAbstract:Rationale and objectives We previously showed that systemic administration of the prototypical alpha-2 noradrenaline (NA) receptor antagonist Yohimbine increases alcohol self-administration and reinstatement. Yohimbine also acts as an agonist of 5-hydroxytryptamine (5-HT) 5-HT1A receptors, which have been shown to be involved in alcohol seeking. Here, we determined the contributions of the alpha-2 and 5-HT1A properties of Yohimbine to its effects on alcohol seeking.
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the crf1 receptor antagonist antalarmin attenuates Yohimbine induced increases in operant alcohol self administration and reinstatement of alcohol seeking in rats
Psychopharmacology, 2007Co-Authors: Peter W Marinelli, Douglas Funk, W Juzytsch, Stephen E Harding, Kenner C Rice, Yavin ShahamAbstract:Yohimbine is an alpha-2 adrenoreceptor antagonist that provokes stress- and anxiety-like responses in both humans and laboratory animals. In rats, Yohimbine increases operant alcohol self-administration and reinstates alcohol seeking. In this study, we assess whether these effects of Yohimbine are attenuated by systemic injections of the corticotrotropin-releasing factor 1 (CRF1) receptor antagonist antalarmin. In Exp. 1, we trained rats to lever press for alcohol solutions (12% w/v, 1 h/day) over several weeks; during training, the response requirement was increased from a fixed-ratio-1 (FR-1) to a fixed-ratio-3 (FR-3) reinforcement schedule. We then tested the effect of antalarmin (10 or 20 mg/kg) on Yohimbine (1.25 mg/kg)-induced increases in operant alcohol self-administration (FR-3 reinforcement schedule). Subsequently, we assessed the effect of antalarmin on Yohimbine-induced increases in plasma corticosterone levels in the previously self-administering rats. In Exp. 2, we trained the rats to self-administer alcohol as in Exp. 1, and after extinction of the alcohol-reinforced lever responding over 13 days, we tested antalarmin’s effect on Yohimbine-induced reinstatement of alcohol seeking. Yohimbine increased operant alcohol self-administration and reinstated alcohol seeking after extinction. These effects of Yohimbine were attenuated by antalarmin. Antalarmin injections in the absence of Yohimbine had no effect on either operant alcohol self-administration or extinction responding. Antalarmin had no effect on Yohimbine-induced corticosterone release in alcohol-experienced rats. These results suggest that extrahypothalamic CRF1 receptors are involved in the effect of Yohimbine on operant alcohol self-administration and on relapse to alcohol seeking and support the notion that CRF1 receptor antagonists should be considered in alcohol addiction treatment.
A D Le - One of the best experts on this subject based on the ideXlab platform.
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role of corticotropin releasing factor in the median raphe nucleus in Yohimbine induced reinstatement of alcohol seeking in rats
Addiction Biology, 2013Co-Authors: A D Le, Douglas Funk, Kathleen M Coen, Zhaoxia Li, Yavin ShahamAbstract:The pharmacological stressor Yohimbine increases ongoing alcohol self-administration and reinstates alcohol seeking in rats. This effect is attenuated by systemic injections of a corticotropin-releasing factor (CRF) antagonist. The brain sites involved in CRF's role in Yohimbine-induced alcohol taking and seeking are unknown. We report that injections of the CRF receptor antagonist d-Phe CRF into the median raphe nucleus (MRN) attenuated Yohimbine-induced reinstatement of alcohol seeking but had no effect on Yohimbine-induced increases in alcohol intake during ongoing self-administration. Results indicate an important role of MRN CRF receptors in Yohimbine-induced reinstatement of alcohol seeking but not Yohimbine-induced increases in alcohol intake.
Leigh C Walker - One of the best experts on this subject based on the ideXlab platform.
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pattern of neural activation following Yohimbine induced reinstatement of alcohol seeking in rats
European Journal of Neuroscience, 2020Co-Authors: Leigh C Walker, Hanna E Kastman, Andrew J LawrenceAbstract:Alcohol use disorders represent an extensive socioeconomic burden, yet effective treatment options are suboptimal. A major hurdle in treating alcohol use disorders is the high rate of relapse. Stress is a major factor that promotes relapse in abstinent drug users; therefore, understanding neural mechanisms that underpin the effects of stress on alcohol seeking is critical. In rodent models of stress-induced relapse, the α2 -adrenoceptor antagonist, Yohimbine, is a widely used chemical stressor to elicit reinstatement of drug/alcohol seeking. However, the exact mechanism how Yohimbine precipitates reinstatement of alcohol seeking and the pattern of neural activation associated with Yohimbine-induced reinstatement is poorly understood. Therefore, we counted Fos-protein positive nuclei across 42 brain regions in alcohol-experienced alcohol preferring rats that received either Yohimbine in the home-cage (1 mg/kg i.p.) or following Yohimbine-induced reinstatement of alcohol seeking. The number of Fos-protein positive nuclei was increased in the prefrontal cortex and extended amygdala after home-cage Yohimbine compared to naive- and vehicle-treated rats. Yohimbine-induced reinstatement increased the number of Fos-protein expressing nuclei in multiple other regions including the thalamus, hypothalamus and hippocampus. We then examined inter-regional correlations in Fos-protein expression for all 42 brain regions, which showed Fos expression was more strongly positively correlated following Yohimbine-induced reinstatement of alcohol seeking, compared to home-cage Yohimbine. These data suggest low-dose Yohimbine in a non-drug-associated context activates stress/impulsivity centres within the brain, whereas Yohimbine in the drug-associated context recruits additional brain regions to drive alcohol seeking.
