Behavioural Brain Research最新文献

{"title":"Brain gray matter volumes and age-related changes in visual episodic memory: Insights from the benson complex figure test","authors":"Maryam Bahri ,&nbsp;Hassan Farrahi ,&nbsp;Maede Bahri ,&nbsp;Hami Mahdavinataj ,&nbsp;Seyed Amir Hossein Batouli","doi":"10.1016/j.bbr.2025.116022","DOIUrl":"10.1016/j.bbr.2025.116022","url":null,"abstract":"<div><div>The visual aspect of episodic memory is essential for the formation of rich narratives of life experiences, but it diminishes as a natural consequence of aging. Thus, pinpointing the brain structures that underlie age-related changes in visual episodic memory will deepen our understanding of how normal aging impacts memory at the neural level. The current study included data from a sample of 252 healthy volunteers from the Iranian brain imaging database (IBID). The participants were aged between 20 and 70 years. The Benson Complex Figure Test (BCFT) was used. Also, structural imaging using a 3 T MRI scanner, was performed, resulting in 85 gray matter volumes. Also, mediation analyses were used to investigate the role of gray matter volumes in the relationship between age and visual episodic memory. The correlation analysis revealed that increasing age was associated with smaller brain volumes in 80 gray matter regions identified and with poorer scores on the copy, recall, and recognition tasks of the Benson Complex Figure Test. Also, visual episodic memory performance on copying and recall tasks showed positive associations with GMV in 3 and 27 particular brain regions. The mediation analysis showed that the GMV in the left medial orbitofrontal, right putamen, and right accumbens areas mediate the age-related differences in recall in the visual episodic memory. Understanding these underlying neural mechanisms can inform the development of targeted diagnostic tools and cognitive interventions aimed at maintaining or enhancing memory function in aging individuals, ultimately improving quality of life. These findings contribute valuable insights to the study of brain aging, memory, and neurodegenerative risk, potentially guiding future research on age-related cognitive decline.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116022"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892102","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":"Developmental differences in reward-learning and its connection to resting-state functional connectivity modeled using a hierarchical Bayesian model","authors":"Zsofia Karlocai ,&nbsp;Johan Vegelius ,&nbsp;Ebba Widegren ,&nbsp;Johan Lundin Kleberg ,&nbsp;David Fällmar ,&nbsp;Nils B. Kroemer ,&nbsp;Malin Gingnell ,&nbsp;Andreas Frick","doi":"10.1016/j.bbr.2025.116008","DOIUrl":"10.1016/j.bbr.2025.116008","url":null,"abstract":"<div><div>Adolescence is a period of heightened sensation-seeking, risk-taking, and reward sensitivity, characterized by structural and functional changes in the brain. Developmental changes in functional connectivity between cortical and subcortical regions may refine communication within reward-related circuitry, influencing learning and decision-making. Here, we compared reinforcement learning behavior and its relationship to resting-state functional connectivity in reward-related circuits in adolescents and adults. Fifty-eight healthy participants (32 adolescents aged 13–16; 26 adults aged 30–40) completed a probabilistic two-armed bandit task and resting-state functional magnetic resonance imaging (fMRI). The learning-related parameters learning rate (α) and inverse temperature (β, an index of the randomness of choices) and their relationship to functional connectivity were modeled from behavioral data using Q learning in a hierarchical Bayesian framework. In the whole sample, learning rate was associated with functional connectivity in several cortico-subcortical pathways, particularly involving the anterior cingulate cortex. Adolescents exhibited lower learning rate and inverse temperature values than adults and had a stronger association between learning rate and fronto-striatal connectivity. Adolescents also showed less tendency to stay with winning options in the task, defined as the proportion of trials where participants repeated the previous choice after a reward. These findings highlight the involvement of the ACC in reward learning and indicate that behavior in a reinforcement learning context is characterized by reduced feedback-driven learning and more variable choice behavior or greater exploration in adolescents compared to adults, and suggest that adolescents rely more on fronto-striatal connectivity during learning.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116008"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888465","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":"Neural correlates of body size estimation: A systematic review and narrative synthesis","authors":"Hayden J. Peel ,&nbsp;Akansha M. Naraindas ,&nbsp;Joyce Guo ,&nbsp;Valentina Cazzato ,&nbsp;Jamie D. Feusner","doi":"10.1016/j.bbr.2025.116020","DOIUrl":"10.1016/j.bbr.2025.116020","url":null,"abstract":"<div><div>Inaccurate body size estimation (BSE), the discrepancy between an individual's actual and perceived body size and shape, is observed not only in clinical conditions like eating disorders and body dysmorphic disorder but also in healthy individuals. Understanding the neural mechanisms that support BSE is timely, given growing interest in perceptual biases and their potential relevance for identifying mechanisms that may be disrupted in clinical populations. However, the field has an incomplete understanding of brain systems functionally involved in BSE ability. To address this, we performed a systematic review, accompanied by a narrative synthesis, to identify brain regions associated with BSE across studies of healthy individuals. Studies using functional neuroimaging were selected if they elicited BSE with a task, contrasted BSE with a control task, and used whole-brain analyses (rather than being restricted to a priori regions of interest). This yielded a set of nine functional magnetic resonance imaging papers. There is relatively consistent involvement of ventral (fusiform/occipitotemporal regions) and dorsal (intraparietal areas) visual pathways, and discrete regions of the prefrontal cortex, suggesting recurring engagement of perceptual and higher-order cognitive systems during BSE. However, current knowledge is limited by the small number and heterogeneity of available studies. We identify both consistent and variable neural correlates of BSE, offering refined targets for future investigations of BSE in clinical populations. Based on these findings, we additionally provide specific suggestions for improving neuroimaging task design for future studies.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116020"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882006","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":"Gut microbiota mediated neuroinflammation in psychiatric disorders: Current perspectives and challenges","authors":"Anushka Nayak,&nbsp;Suranjana Bera,&nbsp;Samprikta Purohit,&nbsp;Chakresh Kumar Jain","doi":"10.1016/j.bbr.2025.116019","DOIUrl":"10.1016/j.bbr.2025.116019","url":null,"abstract":"<div><div>Psychiatric disorders remain a major global health concern, with complex diagnostic criteria and a lack of clear biological markers that continue to challenge therapeutic strategies. Current treatment methods, such as psychotherapy, brain stimulation therapy, and pharmacological interventions, often come with their own set of side effects, thus warranting the need to explore alternative approaches. Emerging research highlights the gut brain axis (GBA) and gut microbiota (GM) as key modulators of brain health and disease. Dysbiosis, a disruption in gut microbial composition, can influence blood brain barrier (BBB) integrity, immune signaling, and microbial metabolite production, collectively modulating neuroimmune homeostasis and contributing to the onset of neuroinflammation. While growing preclinical and clinical evidence links altered GM to depression, anxiety, schizophrenia, bipolar disorder (BD), and autism spectrum disorder (ASD), causal relationships remain incompletely defined. This review examines the established and emerging mechanisms connecting the GM to neuroinflammation underlying psychiatric disorders and evaluates current microbiome targeted interventions, such as diet based strategies, probiotics, next generation probiotics (NGPs), and fecal microbiota transplantation (FMT). We also discuss speculative microbiome engineering approaches and highlight translational limitations that must be addressed before clinical implementation. A holistic approach integrating these strategies with conventional psychiatric treatments could facilitate more effective and personalized interventions.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116019"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877345","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":"Mu-opioid and D1-like dopamine receptor crosstalk in dorsal CA1 hippocampus modulates inflammatory pain in rats","authors":"Farzaneh Nazari-Serenjeh ,&nbsp;Masoumeh Khani ,&nbsp;Ronak Azizbeigi ,&nbsp;Sakineh Salehi ,&nbsp;Abbas Haghparast","doi":"10.1016/j.bbr.2025.116009","DOIUrl":"10.1016/j.bbr.2025.116009","url":null,"abstract":"<div><div>Chronic pain is one of the crucial medical problems worldwide. Recent advancements in neuroscience have highlighted the pivotal role of Mu (μ)-opioid receptors (MOR) and D1-like dopamine receptors (D1Rs) in modulating pain-related behaviors within the dorsal CA1 (dCA1) region of the hippocampus. This study investigated the hypothesis that MOR-D1R interactions in the dCA1 modulate inflammatory pain-related behaviors. A total of 159 adult male Wistar rats received unilateral microinjections of either drug solutions or vehicles. Separate groups were administered varying doses of the D1R agonist SKF38393 (3, 6, 12, and 24 mmol/0.5 μl) into the dCA1. In subsequent experiments, the D1R antagonist (SCH23390; 1.5, 3, 6, 12, or 24 mmol/0.5 μl) was microinjected into the dCA1 area of the hippocampus before injection of an effective dose of SKF38393 (12 mmol/0.5 μl) and morphine (10 mmol/0.5 μl). Finally, rats received the MOR antagonist naloxone (5, 15, and 45 mmol/0.5 μl) before SKF38393 (12 mmol/0.5 μl). Persistent inflammatory pain was assessed using the formalin test (50 µl of 2.5 % formalin) injected subcutaneously into the hind paw. Findings showed that administering SKF38393 into the dCA1 significantly reduced nociceptive responses. However, SCH23390 attenuated the antinociceptive effects of both SKF38393 and morphine. Similarly, naloxone significantly diminished SKF38393-induced pain relief. Results suggest that opioidergic and dopaminergic systems in the dCA1 interact to modulate pain relief. Cross-talk between D1Rs and MOR systems produces augmented analgesic effects, providing new insights for pain management research.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116009"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843247","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":"Causal models and network instability in neurological and psychiatric disorders: Computational and clinical perspectives","authors":"Charles Okanda Nyatega ,&nbsp;Qiang Li ,&nbsp;Weizhi Nie ,&nbsp;Mohammed Jajere Adamu ,&nbsp;Shixin Li","doi":"10.1016/j.bbr.2025.116007","DOIUrl":"10.1016/j.bbr.2025.116007","url":null,"abstract":"<div><div>Self-diagnosis—the capacity of a system to detect and correct its own failures—is a defining property of adaptive systems. In the brain, recursive self-monitoring underlies perception, action, and cognition, but it is also fragile: small imbalances between priors and prediction errors can destabilize entire networks. Similar recursive instabilities are observed in immune collapse during sepsis and in failure modes of artificial intelligence (AI).</div><div>Here, we advance a unified framework of causal models and network instability, integrating predictive coding, computational psychiatry, network neuroscience, immunology, and AI. We analyze Parkinson’s disease and sepsis as full case studies, and schizophrenia and bipolar disorder as psychiatric parallels. Across these conditions, recursive failures manifest as rigid priors, amplified errors, or oscillatory attractors.</div><div>Across neurological, psychiatric, and immune systems, recursive instability emerges when imbalances between prior precision and prediction-error precision destabilize feedback loops, leading to rigid, noise-amplified, or oscillatory dynamics. By framing Parkinson’s disease, sepsis, schizophrenia, and bipolar disorder within a shared instability space, the proposed framework links predictive coding with network-level dynamics across biological domains.</div><div>Clinically, this perspective motivates the development of state-dependent biomarkers and closed-loop interventions—such as adaptive neuromodulation and bioelectronic control—designed to stabilize recursive feedback rather than relying on static, open-loop therapies. Recognizing recursive instability as a transdiagnostic principle highlights shared vulnerabilities across brains, immune systems, and artificial agents, and points toward AI-augmented, causal, and adaptive interventions that integrate computational insight with clinical practice.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116007"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833104","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":"Maternal exercise during pregnancy mitigates behavioral and morphological deficits induced by early-life stress","authors":"Jansen Fernandes ,&nbsp;Eduardo Alves da Silva ,&nbsp;Glauber Menezes Lopim ,&nbsp;Christiane Gimenes ,&nbsp;Kil Sun Lee ,&nbsp;Ricardo Mario Arida","doi":"10.1016/j.bbr.2025.116021","DOIUrl":"10.1016/j.bbr.2025.116021","url":null,"abstract":"<div><div>Maternal separation (MS) is a widely used model of early-life stress that induces long-lasting behavioral and neurobiological alterations in offspring. Maternal exercise during pregnancy has been proposed as a non-pharmacological strategy to counteract these adverse effects. Pregnant Wistar rats were assigned to either a sedentary or exercise group, with the exercise group having free access to a running wheel throughout pregnancy. Offspring were divided into four experimental groups: offspring of sedentary mothers without MS (SedMS−), offspring of sedentary mothers with MS (SedMS+), offspring of exercised mothers without MS (ExMS−), and offspring of exercised mothers with MS (ExMS+). Behavioral assessments, conducted in adulthood starting at postnatal day 90 (P90), included the open field, elevated plus maze, forced swim test, and contextual fear conditioning. Morphological analysis of the hippocampus was performed using isotropic fractionation to quantify total neuronal and non-neuronal cells. Epigenetic changes were evaluated through chromatin immunoprecipitation (ChIP) using anti-acetylated histone H3 and H4, followed by amplification of <em>bdnf</em> exons IV and VI. Maternal separation increased depressive-like behavior and impaired hippocampus-dependent memory, effects that were attenuated by maternal exercise. MS also elevated non-neuronal cell numbers and reduced neuronal cells in the hippocampus, whereas prenatal exercise reversed these alterations. No significant group differences were found in histone acetylation at the <em>Bdnf</em> loci examined. Maternal exercise during pregnancy mitigates behavioral and morphological deficits induced by early-life stress, supporting its neuroprotective role in preserving hippocampal integrity and function. Although no significant epigenetic changes were detected, these findings suggest that maternal physical activity may be a promising intervention to mitigate the long-term neurobiological consequences of early-life adversity.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116021"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882004","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":"Core networks related disrupted effective connectivity and relationship with sleep disturbances in internet gaming disorder","authors":"Longyao Ma ,&nbsp;Bohui Mei ,&nbsp;Xinqi Li ,&nbsp;Mengzhe Zhang ,&nbsp;Hui Zhang ,&nbsp;Jiawen Tian ,&nbsp;Hongyu Zhang ,&nbsp;Yan Lang ,&nbsp;Yarui Wei ,&nbsp;Shaoqiang Han ,&nbsp;Jingliang Cheng ,&nbsp;Yong Zhang","doi":"10.1016/j.bbr.2025.116023","DOIUrl":"10.1016/j.bbr.2025.116023","url":null,"abstract":"<div><h3>Background</h3><div>Internet gaming disorder (IGD) is characterized by increased gaming cravings and sleep disturbances. However, previous studies mainly focused on the relationship between undirected connections among brain regions and IGD features, and rarely reported on directed connections among networks.</div></div><div><h3>Methods</h3><div>This study, based on 66 male IGD subjects and 53 healthy controls (HCs), assessed the effective connectivity (EC) differences of intra- and inter-networks for each subject using spectral dynamic causal modeling from eight interest regions (ROI) in the default mode (DMN), salience (SN), executive control (ECN), and cerebellum networks. The Parametric Empirical Bayes (PEB) framework was used to identify the difference between the two groups. In addition, the mediating role of significant differential EC between IGD severity and sleep quality was further explored.</div></div><div><h3>Results</h3><div>This study observed that four brain networks across HC and IGD subjects showed similarities EC patterns. Compared IGD subjects to healthy controls, abnormal EC in the bottom-up (cerebellum-SN-DMN-ECN) loop was most significantly altered. More importantly, mediation analysis showed that the EC from the medial prefrontal cortex (MPFC) to the anterior cingulate cortex (ACC) partially mediated the impact of IGD severity on sleep quality.</div></div><div><h3>Conclusions</h3><div>This study revealed the disrupted neural causality among DMN, SN, ECN, and cerebellum in IGD subjects and emphasized the potential of DMN-SN interaction in studying sleep disturbances in IGD, which amplify the pathophysiological mechanisms and explain the pathological gaming behaviors of IGD subjects.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116023"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882005","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":"Glucocorticoid antagonist RU486 attenuates microglial activation and ameliorates post-traumatic stress disorder via NLRP3/JAK1/STAT3 pathway","authors":"Bohan Li ,&nbsp;Jingming He ,&nbsp;Yuexing Zhang ,&nbsp;Shenyou Feng ,&nbsp;Zixiang Long ,&nbsp;Zhongyang Li","doi":"10.1016/j.bbr.2025.116004","DOIUrl":"10.1016/j.bbr.2025.116004","url":null,"abstract":"<div><h3>Background</h3><div>Post-traumatic stress disorder (PTSD) is a severe mental health condition characterized by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and neuroinflammation. RU486, a glucocorticoid receptor (GR) antagonist, has been proposed as a potential modulator of neuroinflammation, but its precise mechanisms in PTSD remain unclear.</div></div><div><h3>Methods</h3><div>We established both in vivo single-prolonged stress (SPS) rat models and in vitro lipopolysaccharide (LPS)-stimulated BV-2 microglial models to evaluate the effects of RU486. Transcriptomic sequencing, quantitative PCR (qPCR), Western blot, and immunofluorescence assays were employed to analyze variations in inflammatory markers and signaling pathway molecules, as well as to evaluate therapeutic outcomes.</div></div><div><h3>Results</h3><div>In the SPS rat model, glucocorticoid receptor (GR) expression was upregulated, and the levels of NLRP3, Caspase-1, IL-1β, TNF-α, and IL-6 were elevated, while IL-10 levels were reduced. RU486 treatment alleviated the behavioral abnormalities induced by SPS, decreased serum corticosterone and pro-inflammatory cytokines, and increased IL-10 levels. In BV-2 cells, RU486 downregulated GR expression, modulated inflammatory responses, and inhibited NLRP3 inflammasome-related pathways.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that RU486 significantly suppresses microglial activation and effectively reduces neuroinflammation by modulating the NLRP3/JAK1/STAT3 signaling pathway, thereby alleviating PTSD-like symptoms. These findings highlight RU486 as a promising therapeutic candidate for stress-related inflammatory disorders such as PTSD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116004"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800178","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":"Neurobehavioral and reinforcing effects of pregabalin in mice","authors":"Laurene Dufayet ,&nbsp;Dominique Vodovar ,&nbsp;Jacques Callebert ,&nbsp;Bruno Mégarbane ,&nbsp;Nadia Benturquia","doi":"10.1016/j.bbr.2025.116024","DOIUrl":"10.1016/j.bbr.2025.116024","url":null,"abstract":"<div><div>Pregabalin misuse is increasing, but its psychostimulant and rewarding properties remain unclear, especially regarding sex differences and interactions with opioids. The objectives of this study are to investigate pregabalin’s behavioral and neurochemical effects in male and female mice, including its impact on cognition, social interaction, reinforcement, and cross-sensitization with morphine. CD-1 mice received pregabalin (30–90 mg/kg, i.p.) acutely or for 5 days. Locomotor activity, Y-maze performance, social behavior, and conditioned place preference (CPP) were assessed. Brain monoamine levels were quantified by HPLC. A D1 dopamine receptor antagonist (SCH 23390) was used to explore dopaminergic involvement. Morphine CPP was tested after pregabalin pretreatment. Results showed that in male mice, acute pregabalin induced transient hyperlocomotion and rewarding effects in CPP test, both associated with increased dopamine in the prefrontal cortex and striatum. No psychostimulant or reinforcing effects were observed in female mice. Pregabalin had no impact on memory or general social behavior, though a subset of males displayed aggression, coinciding with elevated serotonin and norepinephrine. Repeated pregabalin dosing produced tolerance without sensitization. Blocking D1 receptors abolished pregabalin-induced CPP. Importantly, pregabalin pretreatment enhanced morphine-induced CPP, suggesting cross-sensitization. Conclusions indicate that pregabalin exerts sex-specific stimulant and rewarding effects in mice, driven by dopaminergic signaling. Its ability to potentiate morphine’s rewarding properties raises concern about abuse potential, particularly in opioid-exposed individuals. These findings highlight the need to consider sex as a biological variable when assessing the addictive risk of pregabalin.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116024"},"PeriodicalIF":2.3,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899196","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}