Psychopharmacology最新文献

{"title":"Intranasal oxytocin blunts amygdala response to negative affective stimuli in males and females with alcohol use disorder: a randomized controlled cross-over trial.","authors":"Sina Vetter, Sophia Schnabel, Matthias Reichl, Lea Sirignano, Valery Grinevich, Anne Koopmann, Rainer Spanagel, Falk Kiefer, Wolfgang Sommer, Patrick Bach","doi":"10.1007/s00213-025-06779-x","DOIUrl":"10.1007/s00213-025-06779-x","url":null,"abstract":"<p><strong>Rationale: </strong>Negative affect plays a prominent role in the maintenance of alcohol use disorder (AUD) and has been identified as a risk factor for relapse to alcohol. To date, however, treatment options that target negative affective states and consecutive relapse risk in AUD are insufficient. Oxytocin (OXY) might be a promising approach for addressing negative affective states and resulting motivation to use alcohol.</p><p><strong>Objectives: </strong>We aimed to investigate the acute effects of 24 I.U. OXY, administered intranasally, compared to matched placebo (PLC) on central processing of negative emotional stimuli in the amygdala in individuals with AUD.</p><p><strong>Methods: </strong>We conducted a randomized double-blind placebo-controlled crossover study in N = 24 individuals with AUD. Amygdala response to emotional stimuli served as primary outcome and was assessed using a validated functional magnetic resonance imaging emotion-processing task. Alcohol craving served as secondary outcome.</p><p><strong>Results: </strong>OXY versus PLC attenuated right amygdala reactivity to fearful and angry emotional face stimuli during the fMRI task (t(33) = 3.32, p_FWE=0.035), while no effect of OXY on amygdala activation was observed during the presentation of geometric figures. In addition, right amygdala reactivity to fearful and angry emotional face stimuli was positively associated with alcohol craving (r =.332, Bias corrected and accelerated 95% confidence interval [95% BCa CI]=-0.044 to 0.624, p =.042).</p><p><strong>Conclusions: </strong>OXY's effects on the neurocircuitry underlying negative affect and craving in AUD support its potential for dampening alcohol craving induced by negative affective states and implicate OXY as a potential future treatment option for AUD.</p><p><strong>Clinicaltrials registry: </strong>DRKS00026218.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1995-2007"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review and meta-analysis of the acute effect of caffeine on attention.","authors":"Kasper Kløve, Anders Petersen","doi":"10.1007/s00213-025-06775-1","DOIUrl":"10.1007/s00213-025-06775-1","url":null,"abstract":"<p><strong>Rationale: </strong>Although there is broad agreement that caffeine provides an acute improvement in attention in the normal population, estimates of effect size vary and the relationship between dose and effect is unclear.</p><p><strong>Objective: </strong>To examine the acute effect of caffeine on attention in a systematic review and meta-analysis.</p><p><strong>Methods: </strong>PsycINFO, PubMed, and Scopus were searched for records published in English with no limits on the year of publication. Studies were included if they were randomized, double-blinded, placebo-controlled, and if they examined the acute effect of pure caffeine on behavioral tests of attention in rested, healthy adults. For every included trial, eligible outcomes were extracted and aggregated to form one composite standardized mean difference (SMD; Hedges' adjusted g) for reaction time and one for accuracy. The SMDs were then combined in random-effects meta-analyses. Additionally, several subgroup analyses were conducted, including meta-regressions on dose-response relationships.</p><p><strong>Results: </strong>Thirty-one trials with a total of 1455 participants were included in the meta-analysis. Significant effects in favor of caffeine were found for both accuracy, g = 0.27, and reaction time, g = 0.28. Subgroup analyses showed that higher doses of caffeine (≥ 200 mg) improved both reaction time and accuracy more than lower doses, but whereas a positive linear dose-response relationship was found for reaction time, a quadratic relationship was found for accuracy. The effect of caffeine was not related to differences in habitual caffeine consumption, task complexity, or which attention network was taxed.</p><p><strong>Conclusion: </strong>The current evidence shows that in the normal population, caffeine acutely enhances attention by improving both reaction time and accuracy. However, whereas higher doses continue to enhance reaction time, accuracy improves only up to a certain point before declining.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1909-1930"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036648","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":"Modulation of strategic status signaling: oxytocin changes men's fluctuations of status products preferences in their female partners' menstrual cycle.","authors":"Honghong Tang, Hongyu Fu, Song Su, Luqiong Tong, Yina Ma, Chao Liu","doi":"10.1007/s00213-025-06783-1","DOIUrl":"10.1007/s00213-025-06783-1","url":null,"abstract":"<p><strong>Rationale: </strong>Women exhibit subtle fluctuations in mating-related behaviors throughout their menstrual cycle, and men are capable of detecting these ovulatory cues. This ability may impact male mating behavior, prompting adjustments in their preferences for consumer products based on these signals. Nonetheless, the potential influence of oxytocin on men's preferences for status products, particularly in the context of their female partners' menstrual cycles, is not yet known.</p><p><strong>Objectives: </strong>This study aims to explore how oxytocin regulates men's responses to their female partners' ovulation in heterosexual romantic relationships by specifically examining changes in their preferences for status consumption.</p><p><strong>Methods: </strong>Through a pilot study (N = 110) and two main studies (N₁ = 789, N₂ = 120), we analyzed how oxytocin influences fluctuations in men's preferences for status products throughout their female partners' menstrual cycles. In Study 1, we examined the impact of the female menstrual cycle on men's preferences for status products. In Study 2, we employed intranasal oxytocin to investigate its modulatory effect on the menstrual cycle's influence.</p><p><strong>Results: </strong>Findings revealed that men demonstrated a lower preference for status products during their partners' ovulation compared to non-ovulatory phases. Furthermore, intranasal oxytocin significantly reduced men's liking for status products during the ovulatory phase, but not during the menstrual phase, with a stronger effect observed among men with a heightened intuitive inclination.</p><p><strong>Conclusions: </strong>These results suggest that men in committed relationships strategically adapt their consumption of status products according to their female partners' menstrual cycles, with oxytocin playing a moderating role in this adaptation and individual differences influencing responses.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2047-2062"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035412","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":"Ethanol consumption prior to cocaine self-administration reduced vulnerability to cocaine reinforcement in socially subordinate female and male monkeys.","authors":"Mia I Allen, Emory Lewis, Cameron F Rough, Michael A Nader","doi":"10.1007/s00213-025-06780-4","DOIUrl":"10.1007/s00213-025-06780-4","url":null,"abstract":"<p><strong>Rationale: </strong>Although ethanol consumption is ubiquitous among individuals who use cocaine, most preclinical work investigating factors that contribute to the development of problematic cocaine use do not incorporate ethanol into their experimental designs. Given that only a subset of individuals who try cocaine go on to develop a cocaine use disorder (CUD) research is needed to identify factors, such as ethanol consumption, that may influence vulnerability to cocaine reinforcement.</p><p><strong>Objectives: </strong>Thus, this study aimed to determine how a history of ethanol self-administration and exposure immediately prior to the first experience with cocaine self-administration influenced the potency of cocaine to function as a reinforcer in socially housed male and female cynomolgus monkeys.</p><p><strong>Methods: </strong>For these experiments, one group of monkeys (n = 7) was trained to self-administer up to 1.5 g/kg of ethanol prior to cocaine self-administration while another group of monkeys (n = 13) remained ethanol-naïve through the study. Acquisition of cocaine self-administration was studied in both groups of monkeys under a fixed-ratio schedule of reinforcement where ascending doses of cocaine were substituted for food pellets. Cocaine ED50 values from the ascending limb were examined statistically.</p><p><strong>Results: </strong>The results showed that subordinate monkeys that self-administered ethanol prior to cocaine self-administration required higher cocaine doses to function as a reinforcer compared with subordinate monkeys not exposed to ethanol.</p><p><strong>Conclusions: </strong>One possible explanation for this finding is that ethanol, due to its acute anxiolytic effects, mitigated the effect of chronic stress in subordinate monkeys and thereby blunted the reinforcing effects of initial cocaine exposure. Future research is needed to examine whether variables such as environmental enrichment or treatment with clinically effective anxiolytics in chronically stressed individuals can modify the initiation and continued use of cocaine.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2009-2019"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753369","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 evolution of N, N-Dimethyltryptamine: from metabolic pathways to brain connectivity.","authors":"Swanti Gupta, Raj K Bhatnagar, Dinesh Gupta, Maharaj Kumari K, Amla Chopra","doi":"10.1007/s00213-025-06777-z","DOIUrl":"10.1007/s00213-025-06777-z","url":null,"abstract":"<p><strong>Rationale: </strong>N, N-Dimethyltryptamine (DMT), a potent serotonergic psychedelic, bridges ancient wisdom and modern science. The mechanisms underlying its powerful psychedelic effects and out-of-body experiences continue to intrigue scientists. The functional role of DMT remains ambiguous. This paper explores the endogenous presence of DMT in the human body and its diverse neuroregulatory functions, which influence hierarchical brain connectivity, and the mechanisms driving its psychedelic effects.</p><p><strong>Objective: </strong>This paper aims to analyze DMT-receptor binding, its effects on neuronal modulation, brain oscillations, and connectivity, and its influence on hallucinations, out-of-body experiences, and cognitive functions.</p><p><strong>Results: </strong>DMT administration induces significant changes in brain wave dynamics, including reduced alpha power, increased delta power, and heightened Lempel-Ziv complexity, reflecting enhanced neural signal diversity. Functional neuroimaging studies reveal that DMT enhances global functional connectivity (GFC), particularly in transmodal association cortices such as the salience network, frontoparietal network, and default mode network, correlating with ego dissolution. The receptor density-dependent effects of DMT were mapped to brain regions rich in serotonin 5-HT2A receptors, supporting its role in modulating consciousness and neuroplasticity.</p><p><strong>Conclusion: </strong>This integrated analysis provides insights into the profound effects of DMT on human cognition, and consciousness, and its role in enhancing natural well-being. As we uncover the endogenous functions of DMT, it becomes clear that the study of its biology reveals a complex interplay between brain chemistry and consciousness.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1931-1953"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005033","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":"Investigating the relationship between gut microbiota and electrocortical signatures of feedback processing: an ERP study.","authors":"Sabrina Lenzoni, Kirsty Hunter, Nadja Heym, Bryony Heasman, Stephanie Blanco, Gemma Walton, Glenn Gibson, Carlos Poveda, Thomas Baguley, Grace Y Wang, Daniel C Mograbi, Alexander Sumich","doi":"10.1007/s00213-025-06878-9","DOIUrl":"https://doi.org/10.1007/s00213-025-06878-9","url":null,"abstract":"<p><strong>Rationale: </strong>Evaluative processing of action outcome is considered crucial for learning and adaptive adjustments of behaviour. Feedback-related negativity (FRN) is an event-related potential elicited by feedback presentation, with implicated neural sources in the anterior cingulate cortex. Bidirectional communications within the brain-gut-microbiota axis modulate cognition and behaviour, and microbial composition has been associated with medial prefrontal cortex function and clinical risk for depression.</p><p><strong>Objectives: </strong>The present study aimed to investigate associations between specific gut microbiota and the FRN.</p><p><strong>Methods: </strong>Twenty-nine healthy participants completed self-report measures of depression and a Faces and Feedback task during electroencephalography recording. Select implicated microbiota genera were enumerated from stool samples (Clostridium, Lactobacillus), along with plasma C-reactive protein (CRP) as an index of systemic inflammation.</p><p><strong>Results: </strong>FRN amplitude for positive feedback was positively correlated with microbiota abundance. The relationship between Clostridium and FRN was confirmed by multilevel modelling analysis, controlling for depression and CRP. The latter was positively associated with FRN amplitude.</p><p><strong>Conclusions: </strong>Findings suggest that the brain-gut-microbiota-axis may modulate or be modulated by self-monitoring processes. The current work provides insights into neurophysiological mechanisms underlying reward processing and indicates novel directions for therapeutic interventions, such as those that modulate the gut microbiome.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966419","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":"CBD attenuates amygdala response to negative emotional stimuli in individuals with alcohol use disorder - a randomized controlled trial.","authors":"Marlen Pfisterer, Anton Teetzmann, Sina Vetter, Joscha Baeßler, Lena Schreckenberger, Judith Zaiser, Manuel Stenger, Patrick Bach","doi":"10.1007/s00213-025-06860-5","DOIUrl":"https://doi.org/10.1007/s00213-025-06860-5","url":null,"abstract":"<p><strong>Rationale: </strong>Negative affect is a key factor in Alcohol Use Disorder (AUD) associated with craving and relapse risk that is insufficiently treated by approved medications. Cannabidiol (CBD) has shown promising effects on negative affect, indicating its potential for addressing the neurocircuitry underlying negative affect in AUD.</p><p><strong>Objectives: </strong>This study investigates CBD's effects on neural response to negative emotional stimuli and subjective alcohol craving in individuals with AUD.</p><p><strong>Methods: </strong>We conducted the first neuroimaging study investigating CBD's effects on neural responses to negative emotional stimuli and craving in AUD. The study was designed as two armed, 1:1 randomized, double blind, parallel group neuroimaging trial, enrolled N = 28 individuals with AUD. It compared the effects of 800 mg oral CBD versus matched Placebo (PLC) on blood oxygenated level dependent (BOLD) response in the amygdala during a validated emotion processing task and explored associations with CBD plasma levels and subjective alcohol craving.</p><p><strong>Results: </strong>CBD versus PLC attenuated bilateral amygdala reactivity to angry and fearful faces (p_FWE <.05, small volume corrected), while CBD showed no effect on amygdala activation during the presentation of neutral shape stimuli. Amygdala response to negative emotional stimuli correlated positively with the extent of subjective alcohol craving (r_{Left Amygdala} =.52, p_FDR =.01; r_{Right Amygdala} =.52, p_FDR =.01) and negatively with CBD plasma levels (r_{Left Amygdala} = -.68, p_FDR = 0.002; r_{Right Amygdala} = -.65, p_FDR = 0.002).</p><p><strong>Conclusion: </strong>In summary, CBD's effects on amygdala reactivity to negative emotional stimuli in individuals with AUD support CBD's potential for modulating emotion-processing circuits in AUD and CBD's treatment potential for craving and relapse driven by negative affective states.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966357","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 process of angiogenesis in neurodegeneration-pathomechanisms and new therapeutic interventions.","authors":"Paulina Kieliszek-Ryba, Anna Jakimiuk, Joanna Kurek, Nicola Simola, Francesca Caria, Iwona Piątkowska-Chmiel, Mariola Herbet","doi":"10.1007/s00213-025-06874-z","DOIUrl":"https://doi.org/10.1007/s00213-025-06874-z","url":null,"abstract":"<p><strong>Objective: </strong>Neurodegenerative diseases are a leading cause of disability worldwide, and recent evidence highlights the role of angiogenesis in their pathophysiology. This review aimed to explore molecular and metabolic links between neurodegeneration and angiogenesis, and to assess the potential of antiangiogenic drugs as therapeutic agents.</p><p><strong>Methods: </strong>A targeted literature search of experimental and clinical studies was performed, focusing on angiogenesis-related mechanisms in neurodegeneration and the effects of antiangiogenic compounds on neuronal and vascular function.</p><p><strong>Results: </strong>Antiangiogenic agents have been shown to promote synaptic plasticity, enhance neurotransmission, and exert anti-inflammatory effects. They also modulate vascular remodeling, which supports optimal cerebral blood flow and nutrient delivery to neurons. These actions may counteract key pathological processes in neurodegenerative diseases and help preserve cognitive and motor function.</p><p><strong>Conclusions: </strong>Modulation of angiogenesis represents a promising therapeutic approach in neurodegenerative disorders. Antiangiogenic drugs may address both vascular and neuronal dysfunction, offering a potential avenue for disease-modifying treatments. Further preclinical and clinical research is needed to validate their safety, efficacy, and long-term benefits.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966369","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 weight reducing effects of naltrexone-bupropion among obese psychiatric and non-psychiatric patients: a systematic review.","authors":"Hafsah Alim Ur Rahman, Muhammad Ahmed Ali Fahim, Unaiza Naeem, Syed Hassan Ahmed, Muhammad Youshay Jawad, Hareem Arshad, Anil Kalyoncu, Mujeeb U Shad, Ahmad Hameed","doi":"10.1007/s00213-025-06873-0","DOIUrl":"https://doi.org/10.1007/s00213-025-06873-0","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity is a global concern leading to significant morbidity and mortality. Naltrexone-Bupropion (NB) is sought to be a favorable medication in obese patients with or without concurrent psychiatric illness. In this systematic review, we have compared NB's role as an obesity management strategy, against placebo and usual care, for overweight and obese psychiatric and non-psychiatric patients.</p><p><strong>Methods: </strong>Cochrane Collaboration and PRISMA guidelines were followed for this study. We searched PubMed/Medline, Cochrane, and Clinicaltrials.gov from inception till June 1, 2024. The primary efficacy outcomes were changes in weight, BMI, and waist circumference.</p><p><strong>Results: </strong>12 RCTs with 5,367 patients were included in the final review. Eight studies used a combination of 32 mg naltrexone and 360 mg bupropion. Weight-related outcomes were reported in 10 studies. Among 5 studies including psychiatric patients, NB showed substantial weight loss. For non-psychiatric patients, NB resulted in significant weight loss and BMI reduction as well. Psychiatric outcomes assessed with BDI-II scores showed greater depression reduction in NB groups. Biomarker outcomes indicated a decrease in LDL and triglycerides, with an increase in HDL for NB groups.</p><p><strong>Conclusion: </strong>Our review highlights NB as a potential option in the management of overweight and obese patients with or without psychiatric comorbidity.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966355","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":"Sex differences in nucleus accumbens circuitry engaged with binge-like ethanol drinking.","authors":"Amy E Chan, Justin Q Anderson, Kolter B Grigsby, Bryan E Jensen, Andrey E Ryabinin, Angela R Ozburn","doi":"10.1007/s00213-025-06875-y","DOIUrl":"10.1007/s00213-025-06875-y","url":null,"abstract":"<p><strong>Rationale: </strong>Women tend to progress from initial alcohol use to Alcohol Use Disorder (AUD) more quickly than men, highlighting the need to study sex differences in models of early-stage alcohol use. In humans and rodents, the nucleus accumbens (NAc) regulates alcohol binge drinking, a risk factor for developing AUD. However, it is unknown whether similar brain regions and NAc inputs are engaged in males and females during binge-like drinking.</p><p><strong>Methods: </strong>We labeled NAc inputs with a viral retrograde tracer (GFP) and quantified whole-brain c-Fos to determine the regions and NAc inputs differentially engaged in male and female mice during binge-like drinking. Mice underwent a 4-day Drinking-in-the-Dark task for either ethanol or water. Immediately following drinking on day 4, periorbital blood samples were collected for determination of blood ethanol concentration, and brains were collected. c-Fos expression and c-Fos + GFP colocalization was quantified for 426 brain areas using SmartAnalytics. We employed several data and network analysis approaches to identify NAc circuits and regions engaged, and network dynamics altered by binge-like drinking.</p><p><strong>Results: </strong>We found that ethanol engaged significantly more NAc inputs in binge-like ethanol drinking females, as compared to males, including various GABAergic and glutamatergic regions. Moreover, we found that binge-like drinking females had 129 brain areas with greater c-Fos than males. Relative to water controls, ethanol increased network modularity and decreased connectivity in both sexes and did so more dramatically in males.</p><p><strong>Conclusion: </strong>Our results support that early-stage binge-like ethanol drinking engages brain regions and NAc inputs and alters network dynamics in a sex-specific manner, which may help to explain the faster transition from initial alcohol use to AUD in women.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}