Genes Brain and Behavior最新文献

{"title":"Untangling Mephedrone-Induced Social Reward in Rats—The Involvement of Oxytocin and Vasopressin V1A Receptors","authors":"Olga Wronikowska-Denysiuk,&nbsp;Łukasz Kurach,&nbsp;Radosław Mlak,&nbsp;Dominika Przygodzka,&nbsp;Tymoteusz Słowik,&nbsp;Barbara Budzyńska","doi":"10.1111/gbb.70057","DOIUrl":"10.1111/gbb.70057","url":null,"abstract":"<p>The rewarding effects of psychostimulants are strongly influenced by social context, yet the underlying neurochemical and neuropeptidergic mechanisms remain unclear. This study examined the role of oxytocin (OT) and vasopressin (AVP) in context-dependent reward induced by subchronic mephedrone treatment in rats. Using classic- and social-conditioned place preference (CPP) we assessed reward and later—monoamine levels in the prefrontal cortex (PFC) and hippocampus, plasma OT and AVP levels, and mRNA expression of oxytocin (OTRs) and vasopressin V1A (AVPV_1ARs) receptors in the nucleus accumbens (NAc) and hippocampus. Pharmacological manipulations of OTRs and AVPV_1ARs were used to evaluate their role in social-CPP. We confirmed that mephedrone (5 mg/kg) induced social- but not classic-CPP. In classic-CPP, mephedrone elevated PFC dopamine, an effect abolished under social conditioning, which instead reduced hippocampal serotonin and noradrenaline. Social context alone lowered baseline monoamines, suggesting dampened neurochemical signaling. Social conditioning increased plasma OT and AVP, whereas mephedrone selectively reversed the OT rise. At the receptor level, mephedrone up-regulated AVPV_1AR mRNA in the hippocampus and OTR mRNA in the NAc, indicating central adaptations distinct from peripheral peptide changes. Behaviorally, social-CPP was abolished by OTR agonism (carbetocin) or AVPV_1AR antagonism (SR49059), while OTR antagonism (L-368,899) or peripheral AVP had no effect. These findings show that mephedrone-induced social reward is shaped by OT and AVP systems. Social context modulates peripheral neuropeptides and engages central receptor adaptations in the hippocampus and NAc, influencing behavioral outcomes. This study provides insights into the neurobiological mechanisms through which the social environment alters drug reward.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148425451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the Strain and Sex Specific Connectome Signatures of Unanesthetized C57BL/6J and DBA/2J Mice Using Magnetic Resonance Imaging","authors":"Tanzil M. Arefin,&nbsp;Hayreddin Said Ünsal,&nbsp;Thomas Neuberger,&nbsp;Nanyin Zhang,&nbsp;Helen M. Kamens","doi":"10.1111/gbb.70060","DOIUrl":"https://doi.org/10.1111/gbb.70060","url":null,"abstract":"<p>Mouse models are an essential tool for understanding behavior and disease states in neuroscience research. While genetic and sex-specific effects have been reported in many neurodegenerative and psychiatric illnesses, these factors may also alter baseline neuroanatomical features of mice. This raises the question of whether the observed changes are related to the disease being studied (i.e., pathological differences) or if there are baseline strain or sex differences that may predispose animals to different responses. Over the past decade, tremendous effort has been made to map neural architecture at various scales; however, the complex relationships, including identifying genetic and sex-specific differences in brain structure and function, remain understudied. To bridge this gap, we used C57BL/6J and DBA/2J mice, two of the most widely used inbred mouse strains in neuroscience research, to investigate strain and sex-specific features of the brain connectome in awake animals using magnetic resonance imaging (MRI). By combining resting-state functional MRI and diffusion MRI, we found that the motor, sensory, limbic, and salience networks exhibit significant differences in both functional and structural domains between C57BL/6J and DBA/2J mice. Further, functional and structural properties of the brain were significantly correlated in both strains. Our results underscore the importance of considering these baseline differences when interpreting brain-behavior interactions in mouse models of human disorders.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148324752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Association Between Mental Disorders and Various Arrhythmias via Mendelian Randomization Methods","authors":"Jingyang Su,&nbsp;Jialin Zhang,&nbsp;Yueyue Ding,&nbsp;Yongjun Ying","doi":"10.1111/gbb.70058","DOIUrl":"10.1111/gbb.70058","url":null,"abstract":"<p>Major depression, bipolar disorder, and schizophrenia are common mental illnesses, and their potential association with arrhythmias has long been a focus of clinical and research interest. To explore the possible causal relationship between these mental disorders and arrhythmias, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis using publicly available GWAS summary statistics. The primary analysis employed the inverse-variance weighted (IVW) method, with sensitivity analyses including MR-Egger regression and the weighted median estimator to assess robustness and address potential pleiotropy. Results indicated that genetic predisposition to major depression was associated with increased risks of atrial fibrillation/flutter (IVW: OR = 1.214, 95% CI: 1.092–1.349, <i>p</i> &lt; 0.001), paroxysmal tachycardia (IVW: OR = 1.493, 95% CI: 1.261–1.769, <i>p</i> &lt; 0.001), and atrioventricular block (IVW: OR = 1.257, 95% CI: 1.147–1.377, <i>p</i> &lt; 0.001). Reverse MR also suggested a modest effect of atrioventricular block on depression risk (IVW: OR = 1.045, 95% CI: 1.011–1.079, <i>p</i> = 0.008). In conclusion, from the perspective of genetic liability and using the MR framework, our analysis supports a causal role of major depression in increasing the risk of several arrhythmias and suggests potential bidirectional causal effects between depression and atrioventricular block.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"∆FOSB in the Nucleus Accumbens Core Is Required for Increased Anxiety, but Not Decreased Social Motivation, Following Estrogen Withdrawal in Female Mice.","authors":"Willow Clayton, May Y Courtney, Lilah E Craig, Helen E Moniz, Alison B Gibbons, Alissa A Valentine, Achint K Singh, Dylan R Gearinger, Eric J Nestler, Laura E Been","doi":"10.1111/gbb.70051","DOIUrl":"10.1111/gbb.70051","url":null,"abstract":"<p><p>During pregnancy, estrogen levels rise dramatically, but quickly drop to prepartum levels following birth and remain suppressed until ovulation resumes. This \"postpartum estrogen withdrawal\" state has been linked to changes in the brain and behavior in humans and rodents. Previous research has demonstrated that following a hormone-simulated pseudopregnancy (HSP), an experimental model of postpartum estrogen withdrawal, female mice show increased anxiety-like behaviors and decreased social motivation. Further, these behavioral changes occur concurrently with an increase in ∆FOSB, a transcription factor associated with stable long-term plasticity, in the nucleus accumbens core. To test whether this increase in ∆FOSB is required for these behavioral changes, we used a viral-mediated gene transfer approach to prevent ∆FOSB-mediated transcription in the NAcC during HSP and found that it reduced the high-anxiety behavioral phenotype in estrogen-withdrawn females. However, preventing ∆FOSB-mediated transcription had little effect on social motivation. Together, these results suggest that postpartum estrogen withdrawal increases ∆FOSB in the NAc core to impact anxiety-like behaviors but not social motivation following estrogen withdrawal.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 3","pages":"e70051"},"PeriodicalIF":2.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Architecture of Addiction-Relevant Behaviors in Outbred Sprague-Dawley Rats Reveals Loci for Anxiety-Like and Nociceptive Traits.","authors":"Apurva S Chitre, Elaine K Hebda-Bauer, Michael A Emery, Fei Li, Khai-Minh Nguyen, Yizhi Wang, Riyan Cheng, Oksana Polesskaya, Stanley J Watson, Jun Li, Huda Akil, Abraham A Palmer","doi":"10.1111/gbb.70053","DOIUrl":"10.1111/gbb.70053","url":null,"abstract":"<p><p>Studies have shown that substance use liability is associated with novelty seeking, anxiety-like behavior, and pain sensitivity. We examined whether common genetic variation in outbred Sprague-Dawley rats explained variation in behavioral measures from three assays with established links to substance use: locomotor response to a novel environment, elevated plus maze, and tail flick. We estimated single-nucleotide polymorphism heritability and performed genome-wide association analyses using permutation-derived significance thresholds (N = 534-654 rats across traits). Heritability estimates ranged from 0.14 to 0.38 across 11 traits. Three independent loci were identified: chromosome 1 for elevated plus maze open-arm behavior (α = 0.05), chromosome 14 for elevated plus maze immobility (α = 0.10), and chromosome 17 for tail flick latency (α = 0.05). Candidate genes included Slc18a2, Gfra1, and Pdzd8 (chromosome 1); Rel and Bcl11a (chromosome 14); and Eci2 and Eci3 (chromosome 17). We compared these loci with our genome-wide association study of a F₂ intercross of selectively bred high- and low-responder rats, originally derived from Sprague-Dawleys, that model individual differences in externalizing and internalizing behavior. The current loci are distinct from the ones identified in the bred lines. This difference likely reflects selection history in the high- and low-responder F₂s, which focused on facets of exploratory locomotion, while loci for anxiety and pain sensitivity traits were identified in the outbreds. This highlights the benefit of using both outbred and selectively bred rats to probe causal variants contributing to individual differences in substance use liability. The current outbred findings implicate monoaminergic signaling, transcriptional control, and lipid metabolism as testable mechanisms for addiction-relevant behaviors.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 3","pages":"e70053"},"PeriodicalIF":2.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147965428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148084913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 3","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taste Preferences Shape Disease Susceptibility via Heritable Nutrient Predispositions: A Behavior–Gene Coevolution Framework","authors":"Xinyang Yan,&nbsp;Longxiao Zhang,&nbsp;Yi Shen,&nbsp;Jinning Song,&nbsp;Jiaxi Li","doi":"10.1111/gbb.70050","DOIUrl":"10.1111/gbb.70050","url":null,"abstract":"<p>Dietary stereotypes driven by health anxiety weaken the assumption that higher taste preference of a food necessarily implies higher intake, potentially mismatching ancestrally imprinted nutrient-handling tendencies with modern diets. We tested whether inherited nutrient predispositions exist and mediate the associations between taste preferences and disease susceptibility. A total of 137 taste-preferences and more than 850 nutrient biomarkers were included for analysis, with seven common gastroduodenal diseases specified as outcomes. Mediation by nutrient predispositions was quantified using a causal-chain model; genetic collinearity along preference–disease links was assessed using Bayesian tests. Maximum-likelihood estimation was applied as a validation analysis for the primary results. External East Asian cohorts were further used to compare and replicate effects observed in the European cohorts. We identified 36 significant causal chains across four gastroduodenal diseases. Mediation involved 14 nutrient or metabolic predispositions. The maximum-likelihood method provided additional confirmation of the initial effect estimates. Cross-ancestry analyses using external cohorts showed directionally consistent effects in East Asian and European cohorts. In comparisons for five foods, only white bread showed concordant associations for both intake and preference with gastric adenocarcinoma risk. Individuals with different taste preferences show marked differences in susceptibility to the same disease, because taste preferences which are inherited across generations shape inter-individual nutrient predispositions. This implicates behavior–gene coevolution as a key driver of divergent disease susceptibility among individuals consuming the same diet. When using intake as the exposure in diet–disease studies, stratifying by taste preference is advisable to mitigate genetic confounding.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whisking Behaviour Reveals Stronger Evidence of Habituation in Homozygous Reeler Mice Compared to Controls","authors":"Ugne Simanaviciute,&nbsp;Aybeniz Ece Cetin,&nbsp;Julien Guy,&nbsp;Helen Tams,&nbsp;Jochen Staiger,&nbsp;Robyn A. Grant","doi":"10.1111/gbb.70049","DOIUrl":"10.1111/gbb.70049","url":null,"abstract":"<p>Reeler mice have a mutation in the reelin gene. As a result, Reeler mice lack cortical layers, yet their brains are still largely functional. However, Reeler mice display strong motor phenotypes, including ataxic gait and tics, and we posit that their whisking behaviour might also be disrupted. We used high-speed video to film and track whisker movements in 9 adult Reeler mice and 9 age-matched controls in three whisker movement assessment tasks, including our established novel object exploration and open field tasks, as well as a new open field habituation task. Overall, whisker movements in Reeler mice were highly conserved during the novel object exploration and open field tasks, and they demonstrated all behaviourally relevant whisking features during exploratory contact with an object, including contact-induced asymmetry, spread reduction, and decreasing whisker speeds following object contact. In the habituation task, whisker angular position and whisker spread decreased between the first consecutive sessions in all mice, suggesting that the animals were less focused on sampling the area as they got more familiar with the environment. However, only Reeler mice were affected by more extensive habituation. We suggest that whisker-dependent sensory function is surprisingly intact in Reeler mice. However, our observed habituation-related changes in Reeler mice whisker movements suggest some behavioural differences in these mice, which is a likely result of their disorganised cortex due to reelin deficiency.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"25 2","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147476209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}