Psychopharmacology最新文献

{"title":"Oxiracetam ameliorates neurological function after traumatic brain injury through competing endogenous RNA regulatory network.","authors":"Liyi Wang, Han Guo, Weidong Zhao, Jiahao Wang, Xuhua Cao","doi":"10.1007/s00213-025-06797-9","DOIUrl":"https://doi.org/10.1007/s00213-025-06797-9","url":null,"abstract":"<p><strong>Rationale: </strong>Oxiracetam (ORC) has been demonstrated to improve neurological function resulting from traumatic brain injury (TBI).</p><p><strong>Objectives: </strong>This study aims to explore the precise molecular mechanism of ORC in the treatment of TBI.</p><p><strong>Methods: </strong>TBI rat model was established and treated with ORC. Modified Garcia score, rotarod test and HE staining were employed to evaluate the neuroprotective effects of ORC. Subsequently, RNA-seq was conducted on the hippocampus of sham, TBI and ORC rats to identify differential expression (DE) lncRNAs and mRNAs. Functional analysis of DE lncRNAs and mRNAs was performed. The real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of DE lncRNAs and DE mRNAs. Western blot was performed to explore important pathway in ceRNA networks.</p><p><strong>Results: </strong>ORC has been demonstrated to effectively improve neurological function in TBI rats. A total of 10 ORC-treated DE lncRNAs and 61 DE mRNAs were obtained. A co-expression network comprising 79 lncRNA-mRNA pairs associated with the treatment of ORC was constructed. Furthermore, an lncRNA-miRNA-mRNA regulated ceRNA network was constructed, comprising 15 mRNAs, 41 miRNAs and 10 lncRNAs. Functional enrichment, qRT-PCR, and Western blot analysis showed that ORC improve neurological function of TBI rats by regulating multiple signaling pathways, including the JAK-STAT/PI3K-Akt pathway, as well as affecting the expression of key genes Prlr, Cdkn1a, and Cldn1.</p><p><strong>Conclusion: </strong>Our study reveals the mechanism of ORC therapy in TBI rats, which mainly relies on the regulation of the JAK-STAT/PI3K-Akt pathway and the influence on the expression of key genes Prlr, Cdkn1a, and Cldn1.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041222","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":"Incremental efficacy systematic review and meta-analysis of psilocybin-for-depression RCTs.","authors":"Nicholas C Borgogna, Tyler Owen, Dan Petrovitch, Jacob Vaughn, David A L Johnson, Louis A Pagano, Stephen L Aita, Benjamin D Hill","doi":"10.1007/s00213-025-06788-w","DOIUrl":"10.1007/s00213-025-06788-w","url":null,"abstract":"<p><strong>Rationale: </strong>Psilocybin is a potentially paradigm-shifting depression intervention. We conducted a systematic review and meta-analysis of psilocybin-for-depression randomized controlled trials (RCTs).</p><p><strong>Objectives: </strong>Systematically assess harm reporting, risk of bias, action mechanism specification, and incremental therapeutic effect sizes in the psilocybin-for-depression RCT literature.</p><p><strong>Methods: </strong>Assessed databases included PsycINFO, CINAHL, Embase, Medline, Web of Science, and Scopus. Search terms \"Psilocybin\" or \"Psychedelic\" were paired with \"Depression\", and \"Randomized Controlled Trial\" or \"RCT\".</p><p><strong>Results: </strong>We identified k = 9 RCTs (k = 10 subgroups) involving n = 602 participants (56% psilocybin). Five studies had low/very low harm quality reporting, opposed to two with high. Most studies demonstrated a high risk of bias. Therapeutic mechanisms of action (MoAs) were discussed in varying detail but rarely assessed in original publications. Psilocybin was moderately superior to controls at reducing depression (g = 0.62; 95% CI = 0.27, 0.98). Effects were heterogenous (τ = .47). Smaller studies evidenced stronger effects that favored psilocybin (Egger's b0 = 3.63, p = .014). Almost all studies documented financial conflicts of interests.</p><p><strong>Conclusion: </strong>Psilocybin demonstrates significant depression reduction relative to controls. However, researchers, clinicians, and stakeholders should consider several contextual factors. Effects were moderate and attenuated in larger and better-controlled studies. Harms reporting and risk of bias was high, though partly driven by unique challenges of psilocybin research. MoAs were variably specified but rarely assessed; suggesting it is unclear how depression is reduced. We advise researchers conduct RCTs with active control conditions, larger samples, and include MoA assessments. Independent RCTs from researchers without financial conflicts of interest are needed.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992798","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":"Embracing change: impermanence acceptance mediates differences in death processing between long-term ayahuasca users and non-users.","authors":"Jonathan David, Aviva Berkovich-Ohana, Yair Dor-Ziderman","doi":"10.1007/s00213-025-06792-0","DOIUrl":"https://doi.org/10.1007/s00213-025-06792-0","url":null,"abstract":"<p><strong>Rationale: </strong>The human psyche's interaction with death fundamentally shapes cognition, emotions, and behavior in both individuals and society. Death-related psychological phenomena have been shown to be influenced by psychedelic interventions. However, the literature lacks a comprehensive assessment of death-related processes in non-clinical settings, the mechanisms underlying long-term changes, and particularly the effects of ayahuasca on these dimensions.</p><p><strong>Objectives: </strong>This cross-sectional study investigates death processing, potential mechanisms of change, and their predictors in ayahuasca veterans (N = 54) compared to non-users (N = 53).</p><p><strong>Methods: </strong>A battery of questionnaires and behavioral assessments were used to evaluate different aspects of death processing in both ayahuasca veterans and non-users. These assessments measured death fear and anxiety, death-acceptance, death-avoidant behaviors, and the accessibility of death-related thoughts. Mediators tested included personality traits, beliefs about the afterlife, trait mindfulness, and the concept of impermanence.</p><p><strong>Results: </strong>The findings demonstrated lower levels of death anxiety, avoidant behavior, and fear of death, as well as greater death acceptance in ayahuasca veterans. Mediation analyses revealed that group differences were not due to demographics, personality, trait mindfulness, ontological beliefs, or impermanence awareness, but rather to impermanence acceptance. Finally, within the ayahuasca group, lifetime ego dissolution experiences predicted the degree of impermanence acceptance.</p><p><strong>Conclusions: </strong>These findings reveal significant, multi-dimensional differences in death processing between ayahuasca and non-psychedelic users. Impermanence acceptance emerged as the key mechanism of change. Additionally, the results highlight the role of acute ayahuasca experiences in producing lasting effects. Future interventions may focus on promoting impermanence acceptance as a strategy for managing existential fear.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980999","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 effect of nicotine on threat avoidance behaviour in healthy non-smokers.","authors":"Madeleine Mueller, Christoph Korn, Jan Haaker","doi":"10.1007/s00213-025-06789-9","DOIUrl":"https://doi.org/10.1007/s00213-025-06789-9","url":null,"abstract":"<p><strong>Rationale: </strong>Developing adaptive strategies for survival relies on distinguishing danger from safety through aversive learning mechanisms. Chronic and acute nicotine exposure have been linked to impaired aversive learning and reduced discrimination between threat and safety. Yet, it is unclear if nicotine also impacts one behavioural consequence of aversive learning, which is the avoidance of threats.</p><p><strong>Objectives: </strong>This preregistered study examines how acute nicotine influences costly avoidance behaviour in non-smokers.</p><p><strong>Methods: </strong>To this end, healthy non-smoking participants (n = 66) received either 1 mg nicotine or a placebo in a double-blind design and underwent an active avoidance task. During acquisition, participants could choose between a safer but longer path to reach their goal or a shorter path (less effort) with a higher chance of receiving an aversive outcome in the form of an electrical stimulus. During uninstructed extinction, both paths no longer contained the risk of an aversive outcome and participants could learn this new safety association by trial and error. Finally, an instructed extinction phase indicated complete safety.</p><p><strong>Results: </strong>Contrary to our pre-registered hypotheses, participants with nicotine intake showed a trendwise reduced avoidance of aversive outcomes, compared to placebo controls. Further analysis revealed however that nicotine did not enhance safety learning during extinction in the nicotine group, as compared to controls.</p><p><strong>Conclusions: </strong>In conclusion, this study strengthens the evidence that nicotine alters learning to identify threat and safety, which is also transferred to avoidance behaviour.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042833","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":"Cognitive flexibility of male rats is increased by augmented punishment in a reversal learning task but ketamine has no detectable long-term effects.","authors":"Anthony N Nist, Stephen J Walsh, Timothy A Shahan","doi":"10.1007/s00213-025-06794-y","DOIUrl":"https://doi.org/10.1007/s00213-025-06794-y","url":null,"abstract":"<p><strong>Rationale: </strong>The probabilistic reversal learning task (PRL) is sometimes used in the context of major depressive disorder (MDD) to assess impairments in cognitive flexibility and feedback sensitivity because behavior in the task is sensitive to pharmacological interventions. Because traditional antidepressants are limited in their effectiveness, new drugs are needed to combat MDD. Ketamine has recently been investigated in the context of probabilistic reversal learning (PRL), but findings regarding its therapeutic efficacy have been mixed. One reason for this could be that almost all non-human versions of the PRL use signaled reward omission (i.e., timeout) as the punishing stimulus. It has long been known that timeout periods do not always function as punishers, and the inclusion of a known effective punishing stimulus could help to produce results of improved translational value.</p><p><strong>Objective: </strong>The present experiment sought to examine the effects of ketamine in the PRL when electric footshocks accompanied timeout periods or not.</p><p><strong>Methods: </strong>A baseline of PRL performance was established with 40 rats in which typical timeouts followed non-rewarded trials. In Phase 2, half the rats also received probabilistic footshock punishment for non-rewarded trials, while the other half continued under baseline conditions. Finally, a single dose of ketamine was administered to half of the rats (n = 10) in each condition (i.e., shock and no shock).</p><p><strong>Results: </strong>Shock punishment increased behavioral persistence and cognitive flexibility in the PRL, but ketamine had no effect beyond causing acute impairments.</p><p><strong>Conclusion: </strong>These results suggest that the conditions of punishment during the PRL can have a significant impact on performance in the task and corroborate previous findings that ketamine may not impact cognitive flexibility or reward processing in healthy rats.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022106","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":"A scoping review of the effects of serotonergic psychedelics on attitudes towards death.","authors":"Noah N T Barr, Kayla J Giese, Sam G Moreton","doi":"10.1007/s00213-025-06787-x","DOIUrl":"https://doi.org/10.1007/s00213-025-06787-x","url":null,"abstract":"<p><strong>Rationale: </strong>Emerging evidence suggests that psychedelic experiences have the potential to change attitudes towards death and reduce death anxiety. Improved attitudes towards death, specifically reduced death anxiety, are of psychological significance for clinical and non-clinical populations alike. Despite this emerging evidence, little is known about the phenomenology of this potential outcome.</p><p><strong>Objectives: </strong>To provide a systematic overview of studies reporting effects of psychedelics on attitudes towards death and death anxiety, thereby identifying any gaps in the current literature and informing suggestions for future research.</p><p><strong>Methods: </strong>MEDLINE, Scopus, PsycINFO, and Web of Science were systematically searched for empirical studies that measured attitudes towards death and death anxiety as an outcomes of classical psychedelic use. There were no limits on the date or design of the study.</p><p><strong>Results: </strong>The thirty-one studies included in the review all reported changes in attitudes towards death and/or changes in death anxiety. Despite finding evidence for psychedelics improving death anxiety, we found significant gaps in the existing research relating to the role of set and setting, potential differences across substances, the underlying psychological mechanisms involved, the potential for worsening of death anxiety, and the role of expectancy and placebo effects.</p><p><strong>Conclusions: </strong>There is largely consistent evidence that psychedelics can often change attitudes towards death and reduce death anxiety. However, less is known about the reliability and strength of these effects, the conditions under which they are likely to emerge and aspects of the experience that best predict them.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014471","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":"Distinct subcircuits within the mesolimbic dopamine system encode the salience and valence of social stimuli.","authors":"Erica A Cross, Johnathan M Borland, Emma K Shaughnessy, Susan D Lee, Vivian Vu, Elizabeth A Sambor, Robert L Meisel, Kim L Huhman, H Elliott Albers","doi":"10.1007/s00213-025-06793-z","DOIUrl":"https://doi.org/10.1007/s00213-025-06793-z","url":null,"abstract":"<p><strong>Rationale: </strong>The mesolimbic dopamine (DA) system (MDS) is the canonical \"reward\" pathway that has been studied extensively in the context of the rewarding properties of food and drugs of abuse. In contrast, little is known about the role of the MDS in the processing of the rewarding and aversive properties of social stimuli.</p><p><strong>Objective: </strong>Social interactions can be characterized by their salience (i.e., importance) and their rewarding or aversive properties (i.e., valence). Here, we test the novel hypothesis that projections from the medial ventral tegmental area (VTA) to the nucleus accumbens (NAc) core code the salience of social stimuli through phasic release of DA in response to rewarding and aversive social stimuli. In contrast, lateral VTA (lVTA) projections to the NAc shell are proposed to encode social valence, with increased tonic DA signaling rewarding interactions and decreased tonic DA signaling aversive ones.</p><p><strong>Methods: </strong>Using DA amperometry, which monitors DA signaling with a high degree of temporal and anatomical resolution, we measured DA release in the NAc core or shell during rewarding and aversive social interactions. Anatomical and functional studies were conducted utilizing retrograde tracing and immunohistochemistry.</p><p><strong>Results: </strong>These studies support the hypothesis that distinct MDS subcircuits (i.e., mVTA to NAc core and lVTA to NAc shell) signal the salience and valence, respectively, of social stimuli.</p><p><strong>Conclusion: </strong>Together, these data provide a novel conceptualization of how functional and anatomical heterogeneity within the MDS detect and distinguish between social salience, social reward, and social aversion.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977785","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":"Assessment of abuse potential of furanylfentanyl and tetrahydrofuranylfentanyl.","authors":"Yuanyuan Chen, Miaojun Lai, Xiangyu Li, Yanling Qiao, Deli Xu, Dan Fu, Bin Di, Peng Xu","doi":"10.1007/s00213-025-06790-2","DOIUrl":"https://doi.org/10.1007/s00213-025-06790-2","url":null,"abstract":"<p><strong>Rational: </strong>Furanylfentanyl and tetrahydrofuranylfentanyl (THF-F) have been emerging in numerous intoxication and overdose cases in recent years. However, there remains a data deficiency regarding the abuse potential of these novel fentanyl analogs.</p><p><strong>Objectives: </strong>This study was designed to systematically assess the abuse potential of furanylfentanyl and THF-F.</p><p><strong>Methods: </strong>In this study, we evaluated the abuse potential of furanylfentanyl and THF-F via the conditioned place preference (CPP), drug self-administration, drug discrimination, and naloxone-precipitated withdrawal experiments with fentanyl as a reference.</p><p><strong>Results: </strong>Results from CPP experiments indicated that furanylfentanyl and THF-F could induce CPP at minimum doses of 0.1 mg/kg and 3 mg/kg, respectively. These doses were 1 time and 30 times that of fentanyl (0.1 mg/kg). Furanylfentanyl elicited stable self-administration responses at 2.5 µg/kg/infusion, whereas THF-F did so at 50 µg/kg/infusion. In the drug-substitution test, furanylfentanyl and THF-F induced the maximum number of infusions at 1.10 µg/kg and 12.5 µg/kg, respectively, which were 1 time and 10 times that of fentanyl (1.21 µg/kg). In drug discrimination tests, all three substances were fully substituted for the discriminative-stimulus effects of heroin dose-dependently. The substitution potency of furanylfentanyl (ED₅₀ = 2.68 µg/kg) was similar to that of fentanyl (ED₅₀ = 2.66 µg/kg), while THF-F (ED₅₀ = 36.32 µg/kg) was 14-fold less potent than fentanyl. Repeated administration of furanylfentanyl and THF-F produced naloxone-precipitated withdrawal symptoms. Thus, furanylfentanyl exhibited comparable potency to fentanyl in terms of rewarding, reinforcing, and subjective effects, while THF-F had reduced potency in these effects. Both of them had physical dependence.</p><p><strong>Conclusions: </strong>Taken together, our study presented new evidence indicating that furanylfentanyl and THF-F exhibit significant abuse potential in rodent models, which provides experimental data for the control. Furthermore, our study offered valuable information for future studies into the addictive properties of structurally modified fentanyl analogs.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977103","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":"MiR-223-3p inhibits hippocampal neurons injury and exerts anti- anxiety/depression-like behaviors by directly targeting NLRP3.","authors":"Wenyuan Wang, Tingting Yang, Na Liu, Lin Yang, Cong Liu, Xiaoxiao Qi, Ning Wang, Mingwei Wang, Yanyong Wang","doi":"10.1007/s00213-025-06763-5","DOIUrl":"https://doi.org/10.1007/s00213-025-06763-5","url":null,"abstract":"<p><p>Anxiety/depression disorders are among the most common neuropsychiatric conditions, and inflammation plays a significant role in their regulation. The involvement of miRNAs in the initiation, progression, and outcomes of anxiety disorders has been widely reported. Here, a decline in miR-223-3p expression was noticed in both IL-8-induced HT-22 cells and a rat model of anxiety/depression disorders treated with chronic unpredictable mild stress (CUMS). Our findings indicate that the overexpression of miR-223-3p significantly alleviates the effects of IL-8 on cell viability, inflammation, and oxidative stress in HT-22 cells, as verified by CCK-8 assay, ELISA assay, and flow cytometry. Through bioinformatics and luciferase reporter assays, NLRP3 was identified as a direct target of miR-223-3p. The inhibition of NLRP3 significantly reduced IL-8-induced damage to hippocampal neurons, while overexpression of NLRP3 reversed the protective effects of miR-223-3p. Moreover, increasing miR-223-3p levels significantly attenuated CUMS-induced anxiety/depression -like behaviors, such as decreased time in center in the open field test (OFT) and decreased time in open arm in the plus-maze test (EPM). The overexpression of miR-223-3p resulted in significant reductions in TNF-α, IL-1β, and SOD levels, an increase in MDA activity, as well as upregulation of cyclic adenosine monophosphate (cAMP), phosphorylated cAMP response element-binding protein (p-CREB), and brain-derived neurotrophic factor (BDNF) in the hippocampus. Overexpression of NLRP3 also reversed the effects of miR-223-3p in vivo. Thus, our research suggests that miR-223-3p can improve anxiety/depression-like behavior and inhibit hippocampal neuronal injury by targeting NLRP3, demonstrating its considerable anti-anxiety potential.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012477","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":"Disruptive effects of d-amphetamine on conditioned sexual inhibition in the male rat.","authors":"Katuschia Germé, Dhillon Persad, Justine Petit-Robinson, Shimon Amir, James G Pfaus","doi":"10.1007/s00213-025-06786-y","DOIUrl":"https://doi.org/10.1007/s00213-025-06786-y","url":null,"abstract":"<p><strong>Rationale: </strong>Male rats trained to associate a neutral odor (almond) with nonreceptive females during their initial sexual experiences develop a conditioned sexual inhibition (CSI) toward the female bearing the olfactory cue when given a choice in a final copulatory preference test between two receptive females (one unscented and one scented) in an open field. We have previously shown that this CSI can be abolished by acute alcohol before the final copulatory preference test.</p><p><strong>Objective: </strong>To examine whether acute treatment with d-amphetamine could also disrupt CSI.</p><p><strong>Methods: </strong>Male rats received 20 alternating conditioning sessions with an unscented receptive female or an almond-scented non-receptive female. Forty minutes prior to the copulatory preference test with two receptive females, one unscented and the other scented (almond extract), males were injected with saline or one of three doses of d-amphetamine (d- 0.5, 1.0, or 2.0 mg/kg). After two reconditioning trials, males were injected with d-amp or saline and exposed to the olfactory cue alone for 1 h. Brains were fixed and processed for immunohistochemical analysis of Fos protein as a marker of neuronal activation. Fos expression was assessed in several brain regions involved in male sexual behavior.</p><p><strong>Results: </strong>Saline-treated males displayed inhibition of copulatory behavior directed toward the scented female. In contrast, and regardless of the dose, males treated with d-amp prior to the final test copulated with both scented and unscented females, indicating that d-amp disrupted the CSI. Exposure to d-amphetamine and the odor alone induced a differential pattern of Fos expression in several brain areas involved in the expression and/or the regulation of male sexual behavior.</p><p><strong>Conclusions: </strong>As observed previously with alcohol, a low dose of d-amphetamine disrupted the display of a CSI by acting on brain regions mediating sexual behavior.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025537","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}