Addiction neuroscience最新文献_第2页

Pavlovian cue-evoked alcohol seeking is disrupted by ventral pallidal inhibition 巴甫洛夫线索诱发的酒精寻求会受到腹侧苍白球抑制的干扰

Addiction neuroscience Pub Date : 2024-11-09 DOI: 10.1016/j.addicn.2024.100186

Jocelyn M. Richard , Bailey Newell , Preethi Muruganandan , Patricia H. Janak , Benjamin T. Saunders

{"title":"Pavlovian cue-evoked alcohol seeking is disrupted by ventral pallidal inhibition","authors":"Jocelyn M. Richard , Bailey Newell , Preethi Muruganandan , Patricia H. Janak , Benjamin T. Saunders","doi":"10.1016/j.addicn.2024.100186","DOIUrl":"10.1016/j.addicn.2024.100186","url":null,"abstract":"<div><div>Cues paired with alcohol can be potent drivers of craving, alcohol-seeking, consumption, and relapse. While the ventral pallidum is implicated in appetitive and consummatory responses across several reward classes and types of behaviors, its role in behavioral responses to Pavlovian alcohol cues has not previously been established. Here, we tested the impact of optogenetic inhibition of ventral pallidum on Pavlovian-conditioned alcohol-seeking in male Long Evans rats. Rats underwent Pavlovian conditioning with an auditory cue predicting alcohol delivery to a reward port and a control cue predicting no alcohol delivery, until they consistently entered the reward port more during the alcohol cue than the control cue. We then tested the within-session effects of optogenetic inhibition during 50 % of cue presentations. We found that optogenetic inhibition of ventral pallidum during the alcohol cue reduced port entry likelihood and time spent in the port, and increased port entry latency. Overall, these results suggest that normal ventral pallidum activity is necessary for Pavlovian alcohol-seeking.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100186"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biased allosteric modulator of neurotensin receptor 1 reduces ethanol drinking and responses to ethanol administration in rodents 神经紧张素受体 1 的偏向异构调节剂可减少啮齿动物的乙醇饮酒量和对乙醇给药的反应

Addiction neuroscience Pub Date : 2024-11-02 DOI: 10.1016/j.addicn.2024.100185

Graydon B. Gereau , Diana Zhou , Kalynn Van Voorhies , Ryan E. Tyler , Jeffrey Campbell , Jackson G. Murray , Ali Alvarez-Pamir , Luke A. Wykoff , Michel A. Companion , Michael R. Jackson , Steven H. Olson , Lawrence S. Barak , Lauren M. Slosky , Ryan P. Vetreno , Joyce Besheer , Zoe A. McElligott

{"title":"Biased allosteric modulator of neurotensin receptor 1 reduces ethanol drinking and responses to ethanol administration in rodents","authors":"Graydon B. Gereau , Diana Zhou , Kalynn Van Voorhies , Ryan E. Tyler , Jeffrey Campbell , Jackson G. Murray , Ali Alvarez-Pamir , Luke A. Wykoff , Michel A. Companion , Michael R. Jackson , Steven H. Olson , Lawrence S. Barak , Lauren M. Slosky , Ryan P. Vetreno , Joyce Besheer , Zoe A. McElligott","doi":"10.1016/j.addicn.2024.100185","DOIUrl":"10.1016/j.addicn.2024.100185","url":null,"abstract":"<div><div>Alcohol use disorders (AUDs) impose an enormous societal and financial burden, and world-wide, alcohol misuse is the 7th leading cause of premature death [<span><span>1</span></span>]. Despite this, there are currently only 3 FDA approved pharmacological approaches for the treatment of AUDs in the United States. The neurotensin (Nts) system has long been implicated in modulating behaviors associated with alcohol misuse. Recently, a novel compound, SBI-553, that biases the action of Nts receptor 1 (NTSR1) activation, has shown promise in preclinical models of psychostimulant use. Here we investigate the efficacy of this compound to alter ethanol-mediated behaviors in a comprehensive battery of experiments assessing ethanol consumption, behavioral responses to ethanol, physiological sensitivity to ethanol, and ethanol metabolism. Additionally, we investigated behavior in avoidance and cognitive assays to monitor potential side effects of SBI-553. We find that SBI-553 reduces ethanol consumption in mice without altering avoidance behavior or novel object recognition. We also observe sex-dependent differences in physiological responses to sequential ethanol injections in mice. In rats, we show that SBI-553 attenuates sensitivity to the interoceptive effects of ethanol (using a Pavlovian drug discrimination task). Our data suggest that targeting NTSR1 signaling may be promising to attenuate alcohol misuse, and adds to a body of literature that suggests NTSR1 may be a common downstream target involved in the psychoactive effects of multiple reinforcing substances.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100185"},"PeriodicalIF":0.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta 腹侧被盖区和黑质紧密团中神经递质定义细胞类型的比例和分布

Addiction neuroscience Pub Date : 2024-10-28 DOI: 10.1016/j.addicn.2024.100183

William S. Conrad , Lucie Oriol , Grace J. Kollman , Lauren Faget , Thomas S. Hnasko

{"title":"Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta","authors":"William S. Conrad , Lucie Oriol , Grace J. Kollman , Lauren Faget , Thomas S. Hnasko","doi":"10.1016/j.addicn.2024.100183","DOIUrl":"10.1016/j.addicn.2024.100183","url":null,"abstract":"<div><div>Most studies on the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) have focused on dopamine neurons and their role in processes such as motivation, learning, movement, and associated disorders such as addiction and Parkinson's disease. However there has been increasing attention on other VTA and SNc cell types that release GABA, glutamate, or a combination of neurotransmitters. Yet the relative distributions and proportions of neurotransmitter-defined cell types across VTA and SNc has remained unclear. Here, we used fluorescent in situ hybridization in male and female mice to label VTA and SNc neurons that expressed mRNA encoding the canonical vesicular transporters for dopamine, GABA, or glutamate: vesicular monoamine transporter (VMAT2), vesicular GABA transporter (VGAT), and vesicular glutamate transporter (VGLUT2). Within VTA, we found that no one type was particularly more abundant, instead we observed similar numbers of VMAT2+ (44 %), VGAT+ (37 %) and VGLUT2+ (41 %) neurons. In SNc we found that a slight majority of neurons expressed VMAT2 (54 %), fewer were VGAT+ (42 %), and VGLUT2+ neurons were least abundant (16 %). Moreover, 20 % of VTA neurons and 10 % of SNc neurons expressed more than one vesicular transporter, including 45 % of VGLUT2+ neurons. We also assessed within VTA and SNc subregions and found remarkable heterogeneity in cell-type composition. And by quantifying density across both anterior-posterior and medial-lateral axes we generated heatmaps to visualize the distribution of each cell type. Our data complement recent single-cell RNAseq studies and support a more diverse landscape of neurotransmitter-defined cell types in VTA and SNc than is typically appreciated.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100183"},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Subregion specific monoaminergic signaling in the female rat striatum during nicotine abstinence 尼古丁戒断期间雌性大鼠纹状体中特定亚区的单胺能信号传导

Addiction neuroscience Pub Date : 2024-10-24 DOI: 10.1016/j.addicn.2024.100184

Erika Lucente, Davide Cadeddu, Christian E Edvardsson, Mia Ericson, Elisabet Jerlhag, Louise Adermark

{"title":"Subregion specific monoaminergic signaling in the female rat striatum during nicotine abstinence","authors":"Erika Lucente, Davide Cadeddu, Christian E Edvardsson, Mia Ericson, Elisabet Jerlhag, Louise Adermark","doi":"10.1016/j.addicn.2024.100184","DOIUrl":"10.1016/j.addicn.2024.100184","url":null,"abstract":"<div><div>Women report more negative effect during nicotine abstinence, a state that may increase the risk of relapse. As monoamines play a key role in mood regulation the aim of this study was to outline changes in monoaminergic signaling during nicotine abstinence. To this end, tissue levels of dopamine and serotonin, as well as the impact displayed by the dopamine D2 receptor agonist quinpirole or 5-HT on excitatory neurotransmission was assessed in female rats subjected to three weeks of nicotine exposure followed by abstinence. Studies were conducted in the nucleus accumbens (nAc), a structure associated with the acute rewarding properties of nicotine, and the dorsolateral striatum (DLS), a region linked to the formation of habits. Data demonstrate that the monoaminergic profile is subregions specific, with higher levels of dopamine in the DLS, but higher levels of serotonin in the nAc. The influence displayed by quinpirole or 5-HT on excitatory neurotransmission was, however, subregion-independent. Repeated exposure to nicotine produced a robust and long-lasting behavioral sensitization to the locomotor stimulatory properties of nicotine, with no sustained changes in monoaminergic profiles when assessed in striatal tissue after five days of abstinence. However, e<em>x vivo</em> electrophysiological recordings demonstrated a subregion specific change in the responsiveness to bath perfused 5-HT, with a blunted response in the DLS, and enhanced synaptic depression in the nAc. In conclusion, while nicotine abstinence was not associated with sustained changes in tissue monoamine levels, repeated nicotine exposure produced subregion-specific neuroplasticity which might contribute to the high risk of nicotine relapse.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100184"},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142527868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oral fentanyl consumption and withdrawal impairs fear extinction learning and enhances basolateral amygdala principal neuron excitatory-inhibitory balance in male and female mice 口服芬太尼和戒断芬太尼会损害雌雄小鼠的恐惧消退学习并增强杏仁核基底外侧主神经元的兴奋-抑制平衡

Addiction neuroscience Pub Date : 2024-10-15 DOI: 10.1016/j.addicn.2024.100182

Anthony M. Downs , Gracianne Kmiec , Zoé A. McElligott

{"title":"Oral fentanyl consumption and withdrawal impairs fear extinction learning and enhances basolateral amygdala principal neuron excitatory-inhibitory balance in male and female mice","authors":"Anthony M. Downs , Gracianne Kmiec , Zoé A. McElligott","doi":"10.1016/j.addicn.2024.100182","DOIUrl":"10.1016/j.addicn.2024.100182","url":null,"abstract":"<div><div>The number of opioid overdose deaths has increased over the past several years, mainly driven by an increase in the availability of highly potent synthetic opioids, like fentanyl, in the un-regulated drug supply. Over the last few years, changes in the drug supply, and in particular the availability of counterfeit pills containing fentanyl, have made oral use of opioids a more common route of administration. Here, we used a drinking in the dark (DiD) paradigm to model oral fentanyl self-administration using increasing fentanyl concentrations in male and female mice over 5 weeks. Fentanyl consumption peaked in both female and male mice at the 30 µg/mL dose, with female mice consuming significantly more fentanyl than male mice. Mice consumed sufficient fentanyl such that withdrawal was precipitated with naloxone, with males having increased withdrawal symptoms as compared to females, despite lower pharmacological exposure. We also performed behavioral assays to measure avoidance behavior and reward-seeking during fentanyl abstinence. Female mice displayed reduced avoidance behaviors in the open field assay, whereas male mice showed increased avoidance in the light/dark box assay. Female mice also exhibited increased reward-seeking in the sucrose preference test. Fentanyl-consuming mice of both sexes showed impaired cued fear extinction learning following fear conditioning and increased excitatory synaptic drive and increased excitability of BLA principal neurons. Our experiments demonstrate that long-term oral fentanyl consumption results in wide-ranging physiological and behavioral disruptions. This model could be useful to further study fentanyl withdrawal syndrome and behaviors and neuroplasticity associated with protracted fentanyl withdrawal.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Perirhinal cortex to the nucleus accumbens circuit in novelty salience following methamphetamine self-administration 甲基苯丙胺自我给药后新奇感显著性中的边缘皮层至脑核回路

Addiction neuroscience Pub Date : 2024-10-14 DOI: 10.1016/j.addicn.2024.100181

Katharine H. Nelson , Dylan L. Freels , Jordan S. Carter , Samuel K. Wood , Adam R. Denton , Jordan L. Hopkins , Sarah T. Goldsmith , Stacia I. Lewandowski , Michael D. Scofield , Carmela M. Reichel

{"title":"Perirhinal cortex to the nucleus accumbens circuit in novelty salience following methamphetamine self-administration","authors":"Katharine H. Nelson , Dylan L. Freels , Jordan S. Carter , Samuel K. Wood , Adam R. Denton , Jordan L. Hopkins , Sarah T. Goldsmith , Stacia I. Lewandowski , Michael D. Scofield , Carmela M. Reichel","doi":"10.1016/j.addicn.2024.100181","DOIUrl":"10.1016/j.addicn.2024.100181","url":null,"abstract":"<div><div>Methamphetamine (meth) use disorder is part of an overarching use disorder that encompasses continued drug seeking and an increased risk of returning to drug use following periods of abstaining. Chronic meth use results in drug-induced cortical plasticity in the perirhinal cortex (PRC) that mediates responses to novelty. PRH projection targets are numerous and include the nucleus accumbens core (NAc). Whereas the PRH-prefrontal cortex is involved in object recognition; we propose that the PRH<img>NAc is involved in novelty salience. Rats underwent short-access (ShA, 1 hr) or long-access (LgA, 6 hr) meth self-administration (SA). We then used a dual viral strategy to inhibit or activate PRH<img>NAc during a novel cue test in which rats were presented with meth‑associated and novel levers. Response patterns on these levers differ depending on the meth access protocol: ShA meth SA results in equal responding on both novel- and meth‑associated levers, whereas LgA meth results in perseverative responding on the meth‑associated lever. Inactivation of the PRH<img>NAc increased responding on the meth lever relative to the novel lever, resulting in a LgA behavioral phenotype. In contrast, activation in LgA rats was without a behavioral effect. We also report that male LgA sucrose SA animals perseverated on the novel lever rather than the meth‑associated lever, which contrast their meth SA counter parts and female specific patterns of behavior. These data open a new line of interest in the role of the PRH<img>NAc circuit in novelty salience through identification of the behavioral relevance of this circuit.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142527867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Post-mortem human brain analysis of the ventral pallidum in alcohol use disorder 对酒精使用障碍患者腹侧苍白球的死后人脑分析

Addiction neuroscience Pub Date : 2024-10-11 DOI: 10.1016/j.addicn.2024.100180

Ameer Elena Rasool , Cormac Peat , Jie Liu, Greg Sutherland, Asheeta A. Prasad

{"title":"Post-mortem human brain analysis of the ventral pallidum in alcohol use disorder","authors":"Ameer Elena Rasool , Cormac Peat , Jie Liu, Greg Sutherland, Asheeta A. Prasad","doi":"10.1016/j.addicn.2024.100180","DOIUrl":"10.1016/j.addicn.2024.100180","url":null,"abstract":"<div><h3>Objective</h3><div>Alcohol use disorder (AUD) is characterised by cycles of alcohol misuse, abstinence, and relapse. The neurobiology of AUD strongly implicates the role of the ventral pallidum (VP) in a variety of drugs of abuse, including alcohol. Pre-clinical studies have demonstrated critical role of parvalbumin and calretinin neurons in the VP in modulating relapse, mood, and motivation. However, there are a limited studies examining the VP at the cellular level in AUD in humans.</div></div><div><h3>Method</h3><div>Post-mortem human brain tissue of AUD (<em>n</em> = 11), remission (<em>n</em> = 6), and control brains (<em>n</em> = 12) were processed for immunohistochemistry to examine the presence and changes in parvalbumin and calretinin neurons in the VP.</div></div><div><h3>Results</h3><div>Similar to pre-clinical rodent models, parvalbumin and calretinin neurons were present in the VP, although no significant difference was found in their number or morphology across all AUD, remission, and control brains.</div></div><div><h3>Conclusion</h3><div>The presence of parvalbumin and calretinin neurons in the VP was confirmed across all groups. This is particularly important as it supports the translatability of previous animal studies regarding the role of parvalbumin and calretinin neurons in AUD, and thus further implicates the VP in the neurobiology of AUD in humans. As there are no distinctions in the number or morphology of these neurons, their significance likely lies in their activity. The presence of both parvalbumin and calretinin in humans, particularly in both control and AUD cases supports translational capacity from preclinical findings is more feasible.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100180"},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142527866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the ventral pallidum in obesity 针对肥胖症的腹侧苍白球

Addiction neuroscience Pub Date : 2024-10-11 DOI: 10.1016/j.addicn.2024.100179

Lisa Z. Fang , Yvan M. Vachez

{"title":"Targeting the ventral pallidum in obesity","authors":"Lisa Z. Fang , Yvan M. Vachez","doi":"10.1016/j.addicn.2024.100179","DOIUrl":"10.1016/j.addicn.2024.100179","url":null,"abstract":"<div><div>Obesity remains a global health challenge with escalating prevalence and imperfect treatments, necessitating novel therapeutic interventions. Hedonic feeding has been identified as a main driver of weight gain, leading to obesity. Therefore, targeting the neural circuits that regulate hedonic intake to reverse or treat obesity may boast a promising strategy.</div><div>The ventral pallidum (VP), a crucial component of the brain's reward circuitry, plays a pivotal role in encoding reward value and reinforcing motivated behaviors, including food intake. This review highlights the work cementing the role of the VP in feeding regulation, and delves into the connectivity between the VP and other brain regions governing energy homeostasis and hedonic feeding behaviors. We also examine the evidence suggesting that dysregulation within the VP contributes to hyperphagia and the development of obesity. Lastly, we discuss the VP as a possible target for focused intervention. Deep brain stimulation for obesity has been under investigation for several years but current electrode targets yield mixed, dissatisfying results.</div><div>While considerable progress has been made in elucidating the VP's role in feeding and obesity, several challenges remain in translating these findings into clinical interventions. Dissecting the diverse neurochemical, neuroanatomical, and projection connectivity of the VP will allow us to harness the full therapeutic potential of VP-based interventions, and may open avenues for developing targeted therapies to address the multifaceted nature of obesity.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100179"},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fentanyl demand and seeking in female rats: Role of the orexin system and estrous cycle 雌性大鼠对芬太尼的需求和寻求：奥曲肽系统和发情周期的作用

Addiction neuroscience Pub Date : 2024-10-09 DOI: 10.1016/j.addicn.2024.100178

David De Sa Nogueira , Chuhyon Corwin , Yogesh Rakholia , Varnitha Punnuru , Meghana Nampally , Amy S. Kohtz , Gary Aston-Jones

{"title":"Fentanyl demand and seeking in female rats: Role of the orexin system and estrous cycle","authors":"David De Sa Nogueira , Chuhyon Corwin , Yogesh Rakholia , Varnitha Punnuru , Meghana Nampally , Amy S. Kohtz , Gary Aston-Jones","doi":"10.1016/j.addicn.2024.100178","DOIUrl":"10.1016/j.addicn.2024.100178","url":null,"abstract":"<div><div>The orexin system plays a major role in drug reward. Orexin-1 receptor (OxR1) blockade reduces fentanyl demand in males. However, there are a number of sex differences in the orexin system, and it is unclear how OxR1 antagonism would decrease fentanyl demand in females. Furthermore, the relationships between the estrous cycle and fentanyl intake are yet to be delineated.</div><div>Here, we conducted a behavioral economics (BE) procedure in female rats to assess the effects of the OxR1 antagonist SB-334867 on fentanyl demand before and after short-(ShA), long- (LgA) or intermittent-access (IntA) self-administration of fentanyl; we also tested the effect of SB-334867 on cued reinstatement of fentanyl seeking. Finally, we measured the impact of the estrous cycle on fentanyl demand, intake and seeking.</div><div>Results showed that in females SB-334867 did not consistently modulate demand for fentanyl before or after chronic access periods. However, SB-334867 at 30mg/kg reduced the number of active lever presses during cued-reinstatement of fentanyl seeking. We also found that fentanyl self-administration disrupted estrous cyclicity, in particular proestrus epochs, an effect that depended on short versus chronic access. Furthermore, extended access to fentanyl shifted the role of progesterone from facilitation of fentanyl demand during short periods, to attenuation of fentanyl demand after long term exposure. These results indicate that an orexin-based therapy in women for treating opioid use disorder must consider prior drug history as well as cycle phase.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100178"},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142527865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effects of amphetamine exposure on stress susceptibility in mice 接触苯丙胺对小鼠应激易感性的影响

Addiction neuroscience Pub Date : 2024-09-28 DOI: 10.1016/j.addicn.2024.100176

Anne K. Eby , Benjamin D. Sachs

{"title":"The effects of amphetamine exposure on stress susceptibility in mice","authors":"Anne K. Eby , Benjamin D. Sachs","doi":"10.1016/j.addicn.2024.100176","DOIUrl":"10.1016/j.addicn.2024.100176","url":null,"abstract":"<div><div>Substance use disorders (SUDs) and their many psychiatric comorbidities, including major depression and anxiety disorders, are characterized by significant sex differences. Although the causes of SUDs and their psychiatric comorbidities remain unknown, stress has been heavily implicated in their etiology. Indeed, one leading hypothesis regarding the basis of clinically observed sex differences in psychopathology argues that differences in stress susceptibility and stress exposure play key roles. Consistent with this, differences in stress susceptibility and reactivity in females compared to males have been documented across multiple species. A wide range of environmental, genetic, and epigenetic factors are also thought to impact stress susceptibility, but whether there are sex differences in the effects of specific susceptibility factors remains understudied. Preclinical work suggests that a history of cocaine exposure can increase susceptibility to stress in males, but whether similar effects occur in females following stimulant exposure has not been established. The current work examined the impact of repeated amphetamine administration on subsequent susceptibility to mild sub-chronic stress in male and female mice. In addition to examining behavior, potential sex differences in the effects of stress and amphetamine on the expression of several genes were evaluated. Our results reveal several significant sex differences in the behavioral effects of amphetamine and stress in the elevated plus maze, forced swim test, and novelty-suppressed feeding test. However, in contrast to our initial hypothesis, a history of amphetamine did not lead to an overall increase in stress susceptibility across multiple tests in males or females.</div></div>","PeriodicalId":72067,"journal":{"name":"Addiction neuroscience","volume":"13 ","pages":"Article 100176"},"PeriodicalIF":0.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142425221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0