Behavioural Brain Research最新文献

{"title":"Non-pharmacotherapy for craving in methamphetamine use disorder: A systematic review and network meta-analysis of randomised controlled trials","authors":"Jisheng Xu ,&nbsp;Xue Li ,&nbsp;Zhicheng Zhu ,&nbsp;Junwei Wang ,&nbsp;Yan Yang ,&nbsp;Xulin Zhou ,&nbsp;Guosi Ying","doi":"10.1016/j.bbr.2026.116084","DOIUrl":"10.1016/j.bbr.2026.116084","url":null,"abstract":"<div><h3>Objectives</h3><div>We evaluated the effects of non-pharmacotherapy on quality of life (QOL) and craving in individuals with methamphetamine use disorder (MUD), ranking the efficacy of various protocols.</div></div><div><h3>Methods</h3><div>We searched multiple databases for randomized controlled trials from inception to Dec 2025. The analysis included 53 studies with 3174 participants, investigating interventions such as exercise, transcranial magnetic stimulation (TMS), transcranial direct current stimulation, behavioral therapy, and acupuncture. The protocol was prospectively registered in PROSPERO (CRD42023443291).</div></div><div><h3>Results</h3><div>For craving reduction, both exercise and TMS demonstrated statistically significant benefits compared to conventional rehabilitation. Combined aerobic/resistance exercise and 10 Hz repetitive TMS targeting the left dorsolateral prefrontal cortex emerged as the most effective specific protocols within their respective categories. Furthermore, preliminary evidence from a limited number of studies indicated that exercise, acupuncture, and behavioral therapy improved patients' QOL.</div></div><div><h3>Conclusion</h3><div>This study confirms that several non-pharmacotherapies are effective for managing craving in MUD. Exercise and TMS are particularly promising for reducing craving. The findings, synthesized within a novel \"Intervention-Circuit-Symptom\" integrative framework, provide a robust evidence base to inform clinical decision-making and guide the future development of MUD treatment guidelines.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116084"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined transcranial electrical stimulation (tES) and cognitive training (CT) for cognitive impairment: Evidence from clinical applications and basic research","authors":"Shu Xing ,&nbsp;Yuan Yuan ,&nbsp;Ping Ren ,&nbsp;Zhuangfei Chen ,&nbsp;Yu Fu","doi":"10.1016/j.bbr.2026.116078","DOIUrl":"10.1016/j.bbr.2026.116078","url":null,"abstract":"<div><div>Cognitive impairment is a serious pathological feature of neuropsychiatric disorders, making the exploration of effective treatments urgent. Recent research shows that combined transcranial electrical stimulation (tES) and cognitive training (CT) can reduce cognitive deficits. This review summarizes studies on neurological disorders that use both clinical patients and rodent models to highlight the underlying neural mechanisms. In patients, this combined approach improves cognitive domains such as attention, working memory, and executive function. Improvements have been observed in patients with mild cognitive impairment (MCI), dementia (e.g., Alzheimer’s disease (AD)), Parkinson’s disease (PD), stroke, traumatic brain injury (TBI), multiple sclerosis, schizophrenia, attention deficit hyperactivity disorder (ADHD) and depression, as well as in healthy populations. In contrast, studies on the combined intervention are lacking in rodent models of disease. However, tES and CT separately improve spatial learning and memory in AD, TBI, schizophrenia, ADHD, and healthy animals, as well as in models of vascular dementia and cerebral ischemia. The combined intervention regulates and remodels functional connectivity in brain networks, and improves cerebrovascular microcirculation and glutamatergic neurotransmission. Importantly, tES and CT may enhance each other through cooperative and complementary effects. In addition, some studies have reported the limited efficacy or negative outcomes of combined and single interventions, which may be due to suboptimal parameters or techniques that fail to target key pathologies. Future clinical trials should explore tES-CT combination strategies targeting disease-specific brain regions. Furthermore, animal studies must be strengthened to elucidate the potential mechanisms and interactions of tES and CT.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116078"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems: A review of human and pre-clinical research","authors":"Kristin A. Felsch,&nbsp;Jessica A. Siegel","doi":"10.1016/j.bbr.2026.116098","DOIUrl":"10.1016/j.bbr.2026.116098","url":null,"abstract":"<div><div>3,4-methylenedioxymethamphetamine (MDMA) is a psychomotor stimulant drug. While much research has examined the effects of MDMA in adults, relatively little research has examined the effects in adolescents. Adolescence is a unique period of brain development, and the effects of MDMA may differ in adolescents compared to adults. In this review, we summarize the literature on the effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems in adolescent rodents and humans. PubMed was searched using predefined criteria, resulting in the evaluation of 1012 articles. Fifty-four articles met the search criteria, 48 of which examined the effects of adolescent MDMA exposure in adolescent rodents and 6 of which examined the effects in adolescent humans. Studies measuring the effects of acute MDMA exposure examine outcome measures following a single exposure to MDMA, and studies measuring the effects of repeated MDMA exposure examine outcome measures at some point following multiple exposures to MDMA. Exposure to acute higher doses of MDMA generally increases locomotor activity and causes impairments in the serotonin neurotransmitter system. The literature on the effects of repeated adolescent MDMA exposure shows conflicting results, and the findings are dependent on the dosing, testing environment, and timing of testing following MDMA exposure. There is a lack of literature examining the effects of MDMA in adolescent females. More research is needed with consistent exposure and dosing paradigms and in female subjects to better understand the effects of adolescent MDMA exposure.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116098"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent Serial Feature Negative and Simple Discrimination Training and Testing in the Mouse","authors":"Negar Ghasem Ardabili ,&nbsp;Jordyn Pettiford ,&nbsp;Alexia Hyde ,&nbsp;Charlotte Airosus ,&nbsp;Anthony L. Riley ,&nbsp;Terry. L. Davidson","doi":"10.1016/j.bbr.2026.116100","DOIUrl":"10.1016/j.bbr.2026.116100","url":null,"abstract":"<div><div>Prior research shows that rats can solve serial feature negative (serFN) and simple discrimination (SD) problems when both are trained concurrently. Furthermore, previous studies indicate that the solution to the serFN (but not the SD) problem depends on the functional integrity of the hippocampus. The present research aimed to determine if mice solve the serFN problem and if this is solved in a manner mediated by inhibitory modulation similar to that seen in rats. Establishing if mice, like rats, can solve the serFN problem using a potentially hippocampal-dependent strategy would provide researchers with greater flexibility when selecting research tools to investigate hippocampal-dependent memory functioning. In Experiment 1, male and female C57BL6J mice were concurrently trained on serFN (Light→Tone−, Tone+) and SD (Clicker+, White Noise−) problems, following which they were injected with cocaine. Animals acquired both discriminations, and subsequent performance was not affected by cocaine administration (unlike impairments reported with rats). Summation and retardation tests argued against a direct inhibitory association for serFN performance and indicated a modulatory form of inhibition. In Experiment 2, male and female C57BL6J mice were similarly trained on serFN and SD problems and then exposed to a Western-style diet for 12 days following training. Animals acquired both discriminations. Western diet consumption selectively impaired serFN performance while leaving SD performance intact (similar to effects reported in rats). Together, these findings demonstrate that mice can solve serFN discrimination. The basis for such learning appears to be modulatory inhibitory control, possibly mediated by the hippocampus.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116100"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxin-induced conditioned disgust responses: Comparing emetine and scopolamine methyl nitrate (SMN) to lithium chloride (LiCl)","authors":"Grace E. Lake ,&nbsp;Lily Wang ,&nbsp;Mustafa Al-Khudairy ,&nbsp;Martin Kavaliers ,&nbsp;Klaus-Peter Ossenkopp","doi":"10.1016/j.bbr.2026.116087","DOIUrl":"10.1016/j.bbr.2026.116087","url":null,"abstract":"<div><div>Chemotherapy patients often develop anticipatory nausea, a learned response produced by an environmental cue triggering nausea in the absence of the emetic stimulus. This can be modelled in rats by pairing the administration of an emetic treatment with exposure to a distinct context. Rats are a non-emetic species, but they are still capable of experiencing nausea, which is observable through the presence of the gaping response. The rat model of anticipatory nausea mainly utilizes lithium chloride (LiCl) to evoke the gaping response, yet various other putative emetic toxins and agents have remained unexplored. The current study determined if emetine, found in ipecac, and scopolamine methyl nitrate (SMN), a derivative of scopolamine, can evoke the conditioned gaping response. Adult male Long Evans rats (<em>n</em> = 40) were administered emetine (5.0 mg/kg, intraperitoneal [i.p.]), SMN (0.5 or 1.0 mg/kg, i.p.), LiCl (127 mg/kg, i.p.), or sodium chloride (NaCl, 0.9 %, i.p., control) before exposure to a distinct context for 30 min, over four conditioning trials, followed by four extinction (drug-free) trials. During the extinction trials, no treatments were administered, and rats were placed directly into the context. Rat behaviour on all of the trials was videotaped and scored for the frequency of the conditioned gaping response. Findings from this study suggest that, in comparison to LiCl, emetine is an effective conditioning stimulus, whereas SMN is not.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116087"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep deprivation-induced TLR4/MyD88/NF-κB pathway dysregulation worsens cognitive impairment in Parkinson’s Disease","authors":"Tianhao Liu ,&nbsp;Yanqing Zhang ,&nbsp;Xinjia Li ,&nbsp;Siyu Liu ,&nbsp;Xiaoran Zhu ,&nbsp;Yanhong Ren ,&nbsp;Rundong Han ,&nbsp;Kechun Liu ,&nbsp;Chen Sun ,&nbsp;Xiuna Ji ,&nbsp;Xiuhua Li","doi":"10.1016/j.bbr.2026.116058","DOIUrl":"10.1016/j.bbr.2026.116058","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is a common neurodegenerative disorder. It has motor symptoms and non motor symptoms, like cognitive impairment, sleep disturbance. Studies show PD patient with sleep disorders show more severe cognitive impairment. To investigate the underlying mechanisms, we used a PD zebrafish model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and simulated insomnia by sleep deprivation (SD). Behavioral tests showed that SD exacerbated cognitive impairment. SD aggravated vascular loss and dopaminergic neuron damage. RT-qPCR analysis revealed the highest expression levels of Toll Like Receptor 4 (tlr-4), Myeloid Differentiation Primary Response 88 (myd88), Nuclear Factor Kappa B (nfκb), Caspase 3 (casp3), BCL2 Associated X, Apoptosis Regulator (bax) in the SD co-treatment group, indicating maximal Toll Like Receptor 4 (TLR4)/Myeloid Differentiation Primary Response 88 (MyD88)/Nuclear Factor Kappa B (NF-κB) pathway activation and apoptosis levels, while Autophagy Related 5 (atg5) expression was lowest, indicating severe autophagy dysfunction. ELISA detected the highest levels of IL-6 and TNF-α, indicating maximal neuroinflammation. This study clarified the mechanism of SD exacerbating PD cognitive impairment: SD upregulates the TLR4/MyD88/NF-κB pathway, which intensifies neuroinflammation and apoptosis and led to autophagy dysfunction. This study revealed the potential mechanism between sleep disturbance and cognitive impairment in PD patients, provided a theoretical basis for the therapies targeting the TLR4/MyD88/NF-κB pathway, holds significant clinical significance for enhancing the quality of life of PD patients.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116058"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the prefrontal-supplementary motor network with online and offline tDCS to modulate disgust: A single-blind and sham-controlled study","authors":"Parastoo Soltani ,&nbsp;Zekrollah Morovati ,&nbsp;Majid Yousefi Afrashteh ,&nbsp;Jakob Fink-Lamotte ,&nbsp;Jaber Alizadehgoradel","doi":"10.1016/j.bbr.2026.116077","DOIUrl":"10.1016/j.bbr.2026.116077","url":null,"abstract":"<div><div>In certain individuals, disgust experience is abnormally high. This heightened sensitivity serves as a cognitive component that can lead to dysfunction in neural circuits related to emotion processing and psychological disorders such as contamination-based obsessive-compulsive disorder. In this single-blind study, 36 individuals with high disgust sensitivity were randomly assigned to three groups: online, offline, and sham. The online group received intensified and repetitive transcranial direct current stimulation (tDCS) while performing a disgust image watching task, whereas the offline and sham groups performed the task at two time points: immediately before (pre-test) and immediately after (post-test) the stimulation session. The offline group received active tDCS, whereas the sham group received placebo tDCS to control for the interval duration. Anodal and cathodal stimulation was applied to the left dorsolateral prefrontal cortex (<span>l</span>-DLPFC; F3) and pre-supplementary motor area (pre-SMA; FC2), respectively. The intervention consisted of 10 sessions of tDCS (2 sessions per day) over 5 days, with a stimulation intensity of 2 mA for 20 min and a 20-minute interval between sessions. The results showed a significant decrease in disgust experience in the online group compared to the offline group, while there was no significant difference between the online and sham groups. Although these findings suggest potential effects of tDCS combined with a task, further studies are necessary to confirm its efficacy.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116077"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between executive dysfunction and mild to severe upper extremity deficits in stroke survivors: A resting state functional near-infrared spectroscopy study","authors":"Man Wang ,&nbsp;Lijun Zhang ,&nbsp;Cheng Xie ,&nbsp;Zhaoxu Hu ,&nbsp;Ru Ya ,&nbsp;Hao Huang ,&nbsp;Changhui Sun ,&nbsp;Yulong Bai ,&nbsp;Yan Hua","doi":"10.1016/j.bbr.2026.116082","DOIUrl":"10.1016/j.bbr.2026.116082","url":null,"abstract":"<div><h3>Objects</h3><div>We aimed to observe the association between executive function and mild to severe upper extremity deficits in stroke survivors. Meanwhile, applying functional Near-Infrared Spectroscopy (fNIRS) to investigate the resting-state functional connectivity (FC) patterns of patients with post-stroke executive impairment (PSEI).</div></div><div><h3>Methods</h3><div>122 stroke survivors with mild to severe upper extremity deficits were enrolled. The Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Stroop color-word test assessed cognitive and executive function. The Fugl-Meyer assessment of the upper extremity (FMA-UE) and Action Research Arm Test (ARAT) assessed motor function. They were collected fNIRS data at the resting state.</div></div><div><h3>Results</h3><div>(1) In patients with mild to moderate upper extremity deficits, PSEI patients exhibited decreased speed/coordination of the upper extremity compared to the NPSEI patients (P &lt; 0.05). The MoCA (r = 0.280, P = 0.047) and FAB (r = 0.358, P = 0.010) were associated with the speed/coordination. PSEI patients showed a decreased FC between the left dorsolateral prefrontal cortex (DLPFC) and the right Pre-Motor and Supplementary Motor Cortex (PreM&amp;SMC), the right primary Somatosensory Cortex (PSMC) (P &lt; 0.05); (2) In patients with severe upper extremity deficits, PSEI patients showed a reduction in FMA and ARAT (P &lt; 0.05). The MoCA was associated with ARAT (r = 0.296, P = 0.016) and FMA-UE (r = 0.317, P = 0.009). The FAB was related to ARAT (r = 0.263, P = 0.033) and FMA-UE (r = 0.295, P = 0.016). PSEI patients did not show a significant change in FC (P ＞ 0.05).</div></div><div><h3>Conclusion</h3><div>Our study suggests that the association between executive function and upper extremity after stroke is associated with the degree of upper extremity deficits. Additionally, the FC among cortical and subcortical brain regions were different with varying degrees of upper extremity deficits in PSEI patients.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116082"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influences of high-definition transcranial direct current stimulation (HD-tDCS) and cognitive reappraisal on emotions and aggression following social exclusion","authors":"Yu Ding ,&nbsp;Chenjia He ,&nbsp;Hanjun Li,&nbsp;Jia Zhang","doi":"10.1016/j.bbr.2026.116083","DOIUrl":"10.1016/j.bbr.2026.116083","url":null,"abstract":"<div><div>Social exclusion can trigger negative emotions and aggressive behavior, while emotion regulation strategies and neuromodulation techniques may mitigate these effects. This study employed a 2 × 2 factorial design to investigate the impacts of high-definition transcranial direct current stimulation (HD-tDCS) and cognitive reappraisal on emotions and aggression following social exclusion. Thirty-two university students were randomly assigned to four groups: active HD-tDCS + cognitive reappraisal, sham HD-tDCS + cognitive reappraisal, active HD-tDCS + no reappraisal, and sham HD-tDCS + no reappraisal. Results showed that active HD-tDCS significantly reduced aggressive behavior in both the Competitive Reaction Time Task and Job-relevant Evaluations Task, likely by enhancing prefrontal regulatory control. Cognitive reappraisal significantly decreased negative emotions but did not directly reduce aggressive behavior, suggesting a dissociation between emotional and behavioral regulation pathways. No significant interaction was found between HD-tDCS and cognitive reappraisal, possibly due to their independent neural mechanisms. These findings highlight the potential of HD-tDCS and cognitive reappraisal as interventions for social exclusion-induced aggression and emotional dysregulation.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116083"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term behavioral and physiological consequences of developmental group size history in mice","authors":"Yoshihiro Tanaka ,&nbsp;Hiroshi Ueno ,&nbsp;Eriko Kitano ,&nbsp;Yu Takahashi ,&nbsp;Sachiko Mori ,&nbsp;Shinji Murakami ,&nbsp;Kenta Wani ,&nbsp;Yosuke Matsumoto ,&nbsp;Motoi Okamoto ,&nbsp;Takeshi Ishihara","doi":"10.1016/j.bbr.2026.116079","DOIUrl":"10.1016/j.bbr.2026.116079","url":null,"abstract":"<div><div>The social environment during development is a critical determinant of adult mental and physical health. While extreme conditions like social isolation are well-studied, the long-term impact of variations in group size during the post-weaning developmental period remains less understood. This study investigates how developmental social density shapes adult behavioral and physiological reactivity, specifically examining whether behavioral phenotypes induced by housing in a larger group persist after the group size is reduced in adulthood. Male C57BL/6 N mice were housed in groups of either six (6–3 group) or three (3–3 group) from postnatal weeks 3–8. At week 8, the number of mice in the 6–3 group cages was reduced to three to match the 3–3 group. Physiological and behavioral assessments, including tests for anxiety-like behavior, locomotor activity, sociality, and working memory, as well as serum corticosterone measurements, were initiated from week 9. Mice with a history of being housed in a larger group (6–3 group) exhibited persistent physiological impairments, including significantly suppressed weight gain, reduced forelimb grip strength, and increased pain sensitivity. Behaviorally, however, the 6–3 group displayed a unique phenotype characterized by reduced anxiety-like behavior in the light/dark transition test and consistently increased spontaneous activity in the open field, social interaction, and Y-maze tests. Furthermore, the 6–3 group showed improved spatial working memory performance and significantly lower serum corticosterone levels compared with the 3–3 group. These findings demonstrate that being reared in a larger group during the critical post-weaning developmental period induces a persistent behavioral and physiological phenotype that remains after the group size is matched to the 3–3 group in adulthood. This state is characterized by behavioral hyper-reactivity and neuroendocrine adjustment, representing a long-term scar of the early-life social environment. This study highlights the profound influence of developmental social history on adult traits and provides a framework for understanding how the early-life social environment dictates the long-term stability of physiological and behavioral phenotypes.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"504 ","pages":"Article 116079"},"PeriodicalIF":2.3,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}