Psychopharmacology最新文献

{"title":"Effects of selected alkaloids on postnatal neurogenesis - in vivo and in vitro studies - literature review.","authors":"Bartłomiej Kwiatkowski, Natalia Biedroń, Urszula Gawryś, Wiktoria Tochman, Alicja Szklarska, Dorota Luchowska-Kocot","doi":"10.1007/s00213-025-06856-1","DOIUrl":"https://doi.org/10.1007/s00213-025-06856-1","url":null,"abstract":"<p><strong>Rationale: </strong>Postnatal neurogenesis is the process of new nerve cell formation that occurs after birth. The disruption of the neurogenesis process is a significant hypothesis in the development of mental disorders and diseases such as depression, anxiety disorders or schizophrenia, as well as neurodegenerative diseases such as Alzheimer's disease.</p><p><strong>Objective: </strong>The objective of this study was to investigate, based on the existing literature, whether naturally occurring alkaloids have an impact on postnatal neurogenesis and, if so, whether this effect is beneficial or detrimental.</p><p><strong>Methods: </strong>An advanced search was conducted using the databases PubMed and Google Scholar, employing the terms \"alkaloid\" AND \"neurogenesis.\" The research focused on in vitro studies using cell lines, including C17.2, HT-22, BV-2, and SH-SY5Y, in addition to in vivo studies involving zebrafish (Danio rerio), Wistar rats and mice.</p><p><strong>Results: </strong>The research indicated that some of the alkaloids have a beneficial impact on postnatal neurogenesis through their pleiotropic mechanisms of action. This is evidenced by their anti-inflammatory and anti-oxidant effects, ability to increase brain-derived neurotrophic factor (BDNF) levels, promotion of synapse formation, and direct effect on neural progenitor cells proliferation. However, some alkaloids have been shown to have a negative effect on postnatal neurogenesis through mechanisms that are the opposite of those mentioned above.</p><p><strong>Conclusion: </strong>There is currently a lack of consensus on whether neurogenesis occurs in Homo sapiens. However, it is known that alkaloids affect the model organisms in different ways, which suggests a potential for these substances to be used therapeutically. Further research is therefore required to investigate this possibility.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of stress and social defeat on neurobiological reinforcement mechanisms across reward to withdrawal in nicotine addiction.","authors":"Kokila Shankar, Sélène Zahedi, Olivier George","doi":"10.1007/s00213-025-06852-5","DOIUrl":"https://doi.org/10.1007/s00213-025-06852-5","url":null,"abstract":"<p><p>Nicotine and cigarette/tobacco use continue to be a prevalent public health issue worldwide. The transition to nicotine addiction occurs through an allostatic cycle involving the stages of binging/intoxication, withdrawal/negative affective states, and preoccupation/anticipation. This review focuses on the psychological, neurobiological, and molecular mechanisms contributing to the negative affective state during withdrawal from nicotine with an emphasis on stress and how social defeat stress can affect these mechanisms. Psychologically, negative affect during withdrawal is thought to contribute to the transition from positive reinforcement of drug-taking to negative reinforcement of nicotine use. Nicotine binding to nicotinic acetylcholine receptors elicits a variety of neuronal signaling throughout the brain, over time producing within- and between-systems neuroadaptations across brain regions that govern reward, anxiety, pain, and stress responses. Continued nicotine use additionally dysregulates myriad molecular signaling pathways that directly affect nicotine intake/aversion and withdrawal-like symptoms. Throughout all of these mechanisms, non-pharmacological stress also plays an important role in mediating much of the negative affect associated with addiction. Social defeat stress increases a variety of neuropeptide signaling that consequently exacerbates drug taking and negative affective states. Understanding the mechanisms through which these stages manifest can better our understanding of addiction disease biology and provide novel avenues for therapeutic targets.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of acute alcohol administration on endocannabinoids and relation to subjective effects.","authors":"Gavin N Petrie, Raegan Mazurka, Elisabeth R Paul, Niclas Stensson, Bijar Ghafouri, Matthew N Hill, Markus Heilig, Leah M Mayo","doi":"10.1007/s00213-025-06843-6","DOIUrl":"https://doi.org/10.1007/s00213-025-06843-6","url":null,"abstract":"<p><strong>Rationale: </strong>Harmful alcohol use remains a significant global public health challenge. Examining variability in the acute subjective effects of alcohol and related neurobiological mechanisms may advance the understanding of susceptibility to harmful alcohol use. Research suggests the endocannabinoid (eCB) system may play an important role in mediating the reinforcing effects of alcohol. This study examined the relationship between alcohol-induced changes in eCB concentrations and the subjective psychoactive effects of acute alcohol consumption.</p><p><strong>Method: </strong>Healthy social drinkers (n = 28, aged 20-35 years) participated in a within-subjects, single-blind, placebo-controlled laboratory alcohol challenge study. Alcohol (0.6 g/kg; with 20% adjustment for women) and placebo sessions were counterbalanced. Subjective alcohol effects were assessed from self-report questionnaires administered pre- and post-dosing, including the Biphasic Alcohol Effects Scale (BAES), Drug Effects Questionnaire (DEQ), and Profile of Mood States (POMS). The eCBs, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), were assessed from blood plasma taken throughout the dosing session.</p><p><strong>Results: </strong>Acute alcohol was associated with an overall decrease in 2-AG concentrations compared to placebo. Further, we found that a drop in 2-AG concentrations was associated with less drug 'liking' and feelings of 'friendliness', whereas under placebo conditions, a rise in 2-AG was associated with a smaller decrease in feelings of 'stimulation' (e.g., feeling energized, talkative). Alcohol did not significantly affect AEA concentrations.</p><p><strong>Conclusion: </strong>Our study provides the first evidence that eCBs may contribute to individual differences in sensitivity to alcohol's reward-related mechanisms by influencing subjective experience, offering insight into the potential role of eCBs in the processes underlying harmful alcohol use.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"96-h methamphetamine self-administration elicits striatal dopamine depletion in male and female rats: a model of binge-like use.","authors":"Bo Jarrett Wood, Ethan D Brackett, Nicole M Hall, Christopher E Cannon, Robert D Dayton, Courtney M Keller, Nicholas E Goeders, Kevin S Murnane","doi":"10.1007/s00213-025-06850-7","DOIUrl":"https://doi.org/10.1007/s00213-025-06850-7","url":null,"abstract":"<p><strong>Background: </strong>Methamphetamine is a psychostimulant with significant public health implications. Chronic methamphetamine use is linked to profound dysregulation of the dopaminergic system, cognitive deficits, and psychiatric symptoms. While traditional experimenter administered \"binge\" dosing models reliably produce dopaminergic neurotoxicity, they fail to capture the volitional, drug intake characteristic of human methamphetamine use. Although self-administration paradigms better reflect human drug-taking behavior, they have yet to consistently reproduce the neurochemical deficits seen in the non-contingent models.</p><p><strong>Methods: </strong>In this study, we employed a very long-access (96-h) methamphetamine self-administration model over eight weeks to evaluate whether contingent, volitional drug intake produces dopaminergic neurotoxicity. Male and female rats were given extended access to methamphetamine (0.06 mg/kg/infusion) for 96-h sessions weekly, with saline-yoked controls. Neurochemical analysis focused on striatal dopamine and metabolites to assess drug-induced alterations.</p><p><strong>Results: </strong>Rats exhibited significant escalation in methamphetamine intake over eight weeks, with no sex differences in total intake. Importantly, striatal dopamine levels were significantly reduced in both male and female methamphetamine self-administering rats compared to saline-yoked controls, representing the first demonstration of dopamine depletion following voluntary administration methamphetamine self-administration. Dopamine depletion was significantly correlated with total methamphetamine intake. Interestingly, no significant changes were observed in dopamine metabolites (DOPAC, HVA).</p><p><strong>Conclusions: </strong>These findings demonstrate that volitional methamphetamine intake under a 96-h access model induces robust dopaminergic deficits, paralleling those seen in non-contingent binge dosing. This model provides a translationally relevant paradigm, capturing both the behavioral and neurobiological aspects of human methamphetamine use, supporting its utility for investigating neurotoxicity and potential treatments.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide, tirzepatide, and retatrutide attenuate the interoceptive effects of alcohol in male and female rats.","authors":"McKinley Windram, Dennis F Lovelock, Joseph M Carew, Caroline G Krieman, Christian S Hendershot, Joyce Besheer","doi":"10.1007/s00213-025-06854-3","DOIUrl":"https://doi.org/10.1007/s00213-025-06854-3","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol use disorder (AUD) remains a major public health challenge, yet effective pharmacotherapies are limited. As such, there is growing interest in repurposing medications with novel mechanisms of action. Glucagon-like peptide-1 (GLP-1) receptor agonists, originally developed for type 2 diabetes, have emerged as promising candidates due to effects on intake regulation and reward processing. GLP-1 receptor agonists, including semaglutide, reduce alcohol intake and relapse-like behaviors in rodent and non-human primate models, and a recent clinical trial found that semaglutide decreased alcohol craving and drinking in adults with AUD. Modulation of the subjective/interoceptive effects of alcohol may contribute to the therapeutic potential of GLP-1 receptor agonists.</p><p><strong>Objectives: </strong>This study used operant drug discrimination in male and female rats to assess how acute and repeated semaglutide treatment affects alcohol's discriminative stimulus (interoceptive) effects. We hypothesized that GLP-1 receptor activation would disrupt alcohol's interoceptive effects. We also evaluated acute treatment with tirzepatide, a dual GLP-1/gastric inhibitory peptide (GIP) receptor agonist, and retatrutide, a triple GIP/GLP-1/glucagon receptor agonist, to determine whether broader receptor activity would differentially influence alcohol's subjective effects.</p><p><strong>Results: </strong>Acute administration of semaglutide, tirzepatide, and retatrutide each attenuated alcohol discrimination, suggesting modulation of subjective alcohol effects. Repeated semaglutide maintained efficacy across the 15-day treatment period; alcohol discrimination returned to control levels three days after treatment cessation.</p><p><strong>Conclusions: </strong>Building on prior work with GLP-1 receptor agonists, these results provide important context for interpreting clinical observations of reduced drinking behavior among individuals receiving this class of therapeutics.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of anti-craving medication on cue reactivity and abstinence in patients undergoing alcohol detoxification: some preliminary evidence from a retrospective event-related potentials study.","authors":"Clémence Dousset, Sonia Sistiaga, Anaïs Ingels, Catherine Hanak, Hendrik Kajosch, Salvatore Campanella","doi":"10.1007/s00213-025-06855-2","DOIUrl":"https://doi.org/10.1007/s00213-025-06855-2","url":null,"abstract":"<p><strong>Rationale: </strong>While medications such as acamprosate, baclofen, or naltrexone have shown promising effects in the treatment of alcohol use disorder (AUD), meta-analyses have yielded conflicting findings regarding their efficacy. This retrospective study examined whether alcohol cue reactivity and its neural correlates could serve as protective factors against relapse in AUD inpatients receiving pharmacological treatment during a three-week detoxification program.</p><p><strong>Method: </strong>Fifty-eight inpatients diagnosed with AUD undergoing a three-weeks detoxification program were selected. These patients received either acamprosate (n = 21), naltrexone (n = 21), or baclofen (n = 16) during their stay. They completed an event-related potential cue-reactivity task at the beginning (T0) and end (T1) of the program. Follow-up data on relapse were collected up to two months post- discharge.</p><p><strong>Results: </strong>The Log-Rank (Mantel-Cox) test ([Formula: see text] (2) = 5.84; p =.059) revealed a marginally significant difference in survival distributions between medications. A significant difference emerged between baclofen and acamprosate groups ([Formula: see text] (1) = 4.73; p =.030), with slower return to alcohol use in the baclofen group. No other significant difference emerged between the acamprosate and naltrexone groups or between the naltrexone and baclofen groups (p >.05). Only the baclofen group showed a significant reduction in oddball P3 amplitude between T0 and T1 (p =.002), suggesting decreased neural cue reactivity.</p><p><strong>Conclusion: </strong>A reduction in neural cue reactivity, observed exclusively in the baclofen group, may act as a protective factor against early relapse in AUD. However, this study was underpowered, and findings should be interpreted cautiously until confirmed in larger prospective investigations.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-methamphetamine working memory decline predicts relapse vulnerability in rats and is rescued by mGlu3 receptor activation.","authors":"Cassandra G Modrak, Peter U Hámor, Marek Schwendt","doi":"10.1007/s00213-025-06847-2","DOIUrl":"https://doi.org/10.1007/s00213-025-06847-2","url":null,"abstract":"<p><strong>Rationale: </strong>Widespread methamphetamine (meth) misuse remains a worldwide public health issue that lacks effective clinical treatment. Besides the high relapse and overdose rates, chronic meth use produces a spectrum of cognitive deficits that further complicate treatment and recovery. Activation of metabotropic glutamate receptor 3 (mGlu3) attenuates drug-seeking behavior and/or improves cognition in several animal models, though its ability to improve meth-associated behavioral deficits has not been explored.</p><p><strong>Objectives: </strong>Here, we evaluated working memory and meth-seeking following abstinence and the effects of mGlu3 activation on such behaviors.</p><p><strong>Methods: </strong>Adult male and female Sprague-Dawley rats were first trained and tested on the operant delayed match-to-sample (DMS) working memory task. Rats then underwent 7 days of short-access (1 h/day) and 14 days of long-access (6 h/day) self-administration or served as drug-naïve controls. During the first 3 weeks of abstinence, rats were re-tested on the DMS task and underwent relapse tests to evaluate meth-seeking behavior. Additionally, the effects of indirect mGlu3 activator 2-PMPA (30 mg/kg, i.p.) on both behavioral measures were assessed.</p><p><strong>Results: </strong>Meth self-administration produced working memory impairment in both sexes. Significantly, the decline in DMS task performance predicted the magnitude of subsequent meth-seeking. 2-PMPA treatment improved DMS task performance in a cognitively impaired subgroup of rats but had no immediate effects on meth-seeking.</p><p><strong>Conclusions: </strong>The current study shows that chronic meth self-administration in rats produces co-occurring working memory deficits and robust meth-seeking, akin to meth use disorder (MUD), and that mGlu3 manipulation holds promise in the treatment of meth-associated cognitive deficits.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmembrane AMPA receptor regulatory protein TARP ɣ-8 is a target of ethanol that regulates self-administration and relapse in mice.","authors":"Sara Faccidomo, Jessica L Hoffman, Julie Lee, Ciarra M Whindleton, Michelle Kim, Seth M Taylor, April Kim, Caroline Richter, Hanna L Seiters, Jacob M Bryant, Ashley Chang, Evan N Smith, Abigail E Agoglia, Susumu Tomita, Melissa A Herman, Clyde W Hodge","doi":"10.1007/s00213-025-06848-1","DOIUrl":"10.1007/s00213-025-06848-1","url":null,"abstract":"<p><strong>Background: </strong>Behavioral pathologies that characterize alcohol use disorder (AUD) are driven by the powerful reinforcing, or rewarding, properties of the drug. We have shown that glutamate AMPA receptor (AMPAR) activity is both necessary and sufficient for alcohol (ethanol) reinforcement. Transmembrane AMPAR regulatory protein (TARP) γ-8 is an essential auxiliary protein that regulates AMPAR expression and activity; however, the role of TARP ɣ-8 in AUD or other forms of addiction remains largely unexplored.</p><p><strong>Objectives: </strong>This study investigated the mechanistic role of TARP γ-8 in operant ethanol self-administration (model of primary reinforcement) and cue-induced reinstatement of ethanol-seeking behavior (model of conditioned reinforcement) using TARP ɣ-8 heterozygous null ( ±) mice. To determine if TARP ɣ-8 signaling is targeted by ethanol use, we evaluated protein expression of TARP γ-8, GluA1, CaMKII, and PSD-95 following ethanol self-administration.</p><p><strong>Results: </strong>A battery of tests evaluating food and water intake, taste preference, anxiety-like behavior, and object recognition memory showed no fundamental behavioral deficits in TARP γ-8 ( ±) mice, and no differences in response to acute ethanol or home-cage drinking as compared to wild-types. However, TARP γ-8 ( ±) mice exhibited significantly reduced acquisition and escalation of operant ethanol self-administration and reduced cue-induced reinstatement of ethanol-seeking behavior, with no differences in parallel sucrose-only controls. In wild-type mice, ethanol self-administration increased TARP γ-8 expression in the amygdala, nucleus accumbens, and hippocampus, and increased GluA1 expression in the amygdala and prefrontal cortex, compared to sucrose controls.</p><p><strong>Conclusion: </strong>These findings highlight the specificity of TARP ɣ-8 regulation of ethanol reinforcement mechanisms and identify this crucial AMPAR auxiliary protein as a target of ethanol in reward-related brain regions, highlighting its potential for development of novel pharmacotherapies for AUD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of genetic deletion of nociceptin/orphanin FQ receptors on spatial and associative memory in rats.","authors":"Anna Maria Borruto, Michele Petrella, Sara De Carlo, Nazzareno Cannella, Friedbert Weiss, Roberto Ciccocioppo","doi":"10.1007/s00213-025-06842-7","DOIUrl":"https://doi.org/10.1007/s00213-025-06842-7","url":null,"abstract":"<p><strong>Rationale: </strong>A growing body of evidence suggests that the N/OFQ-NOP receptor system modulates learning and memory in rodents, with NOP receptor agonists impairing memory and antagonists reversing this effect. Moreover, previous studies on transgenic mice showed that genetic deletion of the NOP receptor enhances spatial and aversive memory.</p><p><strong>Objectives: </strong>To further investigate the role of the NOP receptor system in learning and memory, we used a rat model to assess how genetic deletion of NOP receptors affects spatial and associative memory, comparing it with a wild-type (WT) control group.</p><p><strong>Methods: </strong>Male Wistar Han and NOP^(-/-) rats were tested for spatial memory using the classical Morris Water Maze (MWM) test. A modified MWM was then used to assess cued learning and associative memory. Conditioned place aversion (CPA) further evaluated associative memory. Anxiety-like behavior and motor skills were tested using the Elevated Plus Maze (EPM), Open Field, and Rotarod tests.</p><p><strong>Results: </strong>NOP^(-/-) rats displayed impaired acquisition in the spatial and cued MWM tasks but performed comparably to controls in CPA and spatial MWM retrieval. Notably, NOP^(-/-) rats exhibited an anxiogenic-like phenotype in the MWM, EPM, and OF tests, without showing any motor impairment.</p><p><strong>Conclusions: </strong>Deletion of NOP receptors impairs spatial and associative memory acquisition in the MWM, but this is likely not due to a direct cognitive deficit. Instead, our data suggest that these impairments depend on the anxiogenic-like phenotype observed in NOP^(-/-) rats. These findings highlight the complex interplay between anxiety and memory processes in the context of NOP receptor signaling.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemogenetic activation of medial prefrontal cortex projections to the nucleus accumbens shell suppresses cocaine-primed reinstatement in EcoHIV infected mice.","authors":"Qiaowei Xie, Mark D Namba, Rohan Dasari, Lauren A Buck, Christine M Side, Samuel L Goldberg, Kyewon Park, Joshua G Jackson, Laura Giacometti, Jacqueline M Barker","doi":"10.1007/s00213-025-06849-0","DOIUrl":"10.1007/s00213-025-06849-0","url":null,"abstract":"<p><p>HIV is highly comorbid with cocaine use disorder (CUD). Relapse is a major challenge in the treatment of CUD, and people living with HIV (PLWH) exhibit shorter time to relapse. One driver of relapse may be re-exposure to cocaine, which can be modeled in rodents using cocaine-primed reinstatement. This process involves neuroadaptations within the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) shell, regions that mediate cocaine reward learning and relapse-related behavior. HIV infection interacts with cocaine to alter corticostriatal circuits, which may further dysregulate cocaine seeking. To investigate the impact of HIV infection on cocaine reward learning and reinstatement and the role of mPFC-NAc circuits, we utilized the EcoHIV mouse model, a chimeric form of HIV-1 which can infect wild-type mice. Our findings demonstrate that EcoHIV infection enhances cocaine-primed reinstatement. We also observed increased cocaine-induced expression of the cellular activation marker cFos in the NAshell in EcoHIV-infected mice. Given the role of the mPFC-NAshell circuit in cocaine-seeking behaviors, we further demonstrated that chemogenetic activation of this circuit could reverse the behavioral deficits induced by EcoHIV. We propose that HIV infection contributes to neuroadaptations in the mPFC-NAshell circuit, and enhancing its activity may inhibit relapse-related behavior. These findings indicate that key neuronal circuits underlying cocaine reinstatement are similarly implicated in HIV infection and suggest potential strategies for managing relapse in PLWH.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}