Behavioural Brain Research最新文献

{"title":"Combining network pharmacology, machine learning, molecular docking, molecular simulation dynamics and experimental validation to explore the mechanism of Zhenwu decoction in treating major depression through TNF-α pathways","authors":"Xinyu Zhou ,&nbsp;Yan Gao ,&nbsp;Sashuang Liu ,&nbsp;Yijing Zhao ,&nbsp;Zhen Wang ,&nbsp;Dexiang Liu","doi":"10.1016/j.bbr.2025.115997","DOIUrl":"10.1016/j.bbr.2025.115997","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is a severe psychophysiological condition characterized by cognitive decline, low energy, weight loss, insomnia, and increased suicide risk, posing a significant burden on global health. Zhenwu decoction (ZWD), a traditional Chinese medicine, has shown therapeutic potential in alleviating MDD symptoms. However, its complex composition has limited the understanding of its underlying pharmacological mechanisms. This study aimed to explore the antidepressant mechanisms of ZWD in the treatment of MDD.</div></div><div><h3>Methods</h3><div>Active compounds and potential targets of ZWD were identified through database screening and network pharmacology analysis. These targets were intersected with MDD-related genes to construct a protein–protein interaction network. Core targets were further refined using random forest algorithms. Molecular docking and molecular dynamics simulations were employed to evaluate the binding affinity and stability between key compounds and core targets. Experimental validation was conducted in a lipopolysaccharide (LPS)-induced mice model of depression using behavioral testing, measurement of inflammatory cytokines, and gene expression analysis.</div></div><div><h3>Results</h3><div>Network pharmacology and machine learning identified TNF-α signaling as key pathways in the antidepressant effects of ZWD. Enrichment analysis highlighted the involvement of Lipid and atherosclerosis, the IL-17 signaling pathway. Core targets, including PPARG, F10, AR, TNF, PIK3CG, ADH1C, and GABRA6, were predicted to mediate its effects. Molecular docking and dynamics simulations confirmed strong binding of ZWD components, especially kaempferol, to TNF-α, inhibiting its expression. In <em>vivo</em>, ZWD improved anxiety/depressive-like behaviors in LPS-treated mice, evidenced by better performance in the behavioral tests. ZWD also reduced neuroinflammation, with decreased <em>Tnf-α</em> levels, and reduced IBA-1 and GFAP staining, indicating reduced microglial and astrocyte activation. These results suggest that ZWD alleviates depression through modulation of TNF-α–mediated inflammation.</div></div><div><h3>Conclusions</h3><div>These findings suggest that ZWD exerts antidepressant effects primarily by modulating TNF-α–mediated inflammatory pathways, providing a comprehensive molecular and experimental framework supporting its clinical potential in MDD treatment.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 115997"},"PeriodicalIF":2.3,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833156","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":"Chronic administration of berberine attenuates depressive-like behavior in rats subjected to chronic unpredictable mild stress combined with ACTH treatment: Role of nitrergic system","authors":"Sharvari Deshmukh ,&nbsp;Biru B. Dudhabhate ,&nbsp;Dipak K. Sahare ,&nbsp;Dadasaheb M. Kokare ,&nbsp;Yashashree A. Gadhikar","doi":"10.1016/j.bbr.2025.116006","DOIUrl":"10.1016/j.bbr.2025.116006","url":null,"abstract":"<div><div>Major depressive disorder (MDD) remains a significant clinical concern because of its poor response to conventional antidepressants. Berberine, an isoquinoline alkaloid of natural origin has shown promising antidepressant-like effects in preclinical models. However, the mechanism by which berberine ameliorates depressive-like behavior has not been clearly studied. Herein, we examined the effect of berberine on depression induced by chronic unpredictable mild stress (CUMS) combined with adrenocorticotropic hormone (ACTH) treatment in rats and explored the role of the nitrergic system in its mechanism. The CUMS (42 days) with ACTH (14 days) -treated rats showed decreased sucrose preference, percentage of time spent in the central area of open field tests, exploration towards the novel object in the novel object recognition test, and increased immobility time in the forced swim test. There was increased neuronal nitric oxide synthase (nNOS) immunoreactivity in the paraventricular nucleus of hypothalamus (PVN), serum corticosterone level, and reduced dopamine and serotonin levels of the hippocampus in the CUMS + ACTH-treated rats. The chronic intraperitoneal (i.p.) administration of berberine (5 mg/kg; i.p.) for 14 days to the CUMS + ACTH-treated rats reversed all these parameters. Furthermore, the administration of sodium nitroprusside (SNP; 1 mg/kg) prior to the berberine treatment in CUMS + ACTH-treated rats blocked its positive effect. The findings suggest that berberine treatment may exert its antidepressant-like and memory-enhancing effects, at least in part, by attenuating hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, potentially through the involvement of nitrergic signaling.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 116006"},"PeriodicalIF":2.3,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809157","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":"Evolutionary explanations of depression and cognitive control dysfunction: A literature review","authors":"Akihiro Masuyama","doi":"10.1016/j.bbr.2025.116001","DOIUrl":"10.1016/j.bbr.2025.116001","url":null,"abstract":"<div><div>Cognitive control dysfunction, including impairments in inhibition, shifting, updating, and the balance between proactive and reactive control, is a robust feature of depression. Although these patterns are well documented, their origins and possible functions remain debated. This narrative review asks whether recurrent depressive cognitive-control profiles can be interpreted, in part, through evolutionary frameworks. Integrating Social Rank Theory, the Analytical Rumination Hypothesis, and Social Bargaining Theory, this review maps depressive control patterns onto putative functions related to hierarchy management, complex problem solving, and social support recruitment. Rather than treating cognitive control dysfunction as a unitary deficit, this review synthesizes component-level evidence and network perspectives to argue that specific configurations of control processes and attentional biases may reflect context-sensitive trade-offs. These hypotheses are situated within broader explanations, including evolutionary mismatch, byproduct accounts, stress–inflammation pathways, and developmental and cultural contingencies. This broader framing emphasizes that conditionally functional states can still be costly and clinically impairing in contemporary environments. Overall, this review proposes an integrative framework linking computational aims, cognitive algorithms, and neural implementations to evolutionary hypotheses, clarifying why particular cognitive-control profiles may recur in depression and resist change. Clinically, this framework motivates using cognitive control training and cognitive-behavioral interventions as mechanistic probes to identify and modify the control parameters and network couplings most relevant to a given depressive profile.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 116001"},"PeriodicalIF":2.3,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803126","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":"2025-12-18","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":"Environmental enrichment partially rescues neurodevelopmental milestone delays in the prenatal VPA rat model of autism spectrum disorders","authors":"Oussama Duieb,&nbsp;Ayoub Rezqaoui,&nbsp;Soufiane Boumlah,&nbsp;Laila Ibouzine-Dine,&nbsp;Hasnaa Mallouk,&nbsp;Soumia Ed-Day,&nbsp;Aboubaker Elhessni,&nbsp;Abdelhalem Mesfioui","doi":"10.1016/j.bbr.2025.116003","DOIUrl":"10.1016/j.bbr.2025.116003","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by early sensorimotor delays, which often precede core social deficits as well as restricted and repetitive behaviors. Environmental enrichment (EE) is a promising behavioral intervention for ASD; however, its potential to prevent these earliest neurodevelopmental disruptions remains unexplored. This study investigated whether sustained EE could prevent early milestone delays in a prenatal valproic acid (VPA) rat model of ASD. Female Wistar rats were housed in standard (SH) or EE conditions for eight weeks, beginning two weeks before conception and continuing through lactation. Dams received a single injection of VPA (500 mg/kg) or saline on gestational day 12.5. Offspring were assessed daily from postnatal day (PND) 1–21 for the acquisition of physical and sensorimotor milestones. EE significantly mitigated VPA-induced delays in a subset of key neurodevelopmental milestones. While EE did not fully normalize development to control levels, a composite neurodevelopmental score revealed that EE significantly attenuated the global impairment induced by VPA. These findings demonstrate that preconception-perinatal EE confers partial protection against functional neurodevelopmental deficits in a predictive ASD model, highlighting its potential as a preventive strategy targeting the earliest manifestations of neurodevelopmental disruption.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 116003"},"PeriodicalIF":2.3,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797739","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 effect of chronic stress on sensitivity to dexamethasone treatment of HPA axis gene expression in C57Bl/6 mice","authors":"Rasha Salman ,&nbsp;Polina Ritter ,&nbsp;Yuliya Ryabushkina ,&nbsp;Julia Khantakova ,&nbsp;Natalya Bondar","doi":"10.1016/j.bbr.2025.116000","DOIUrl":"10.1016/j.bbr.2025.116000","url":null,"abstract":"<div><div>Chronic social stress is a major risk for psychopathologies such as depression, often leading to altered hypothalamic-pituitary-adrenal (HPA) axis function and glucocorticoid resistance. This study examines how chronic social defeat stress (CSDS) affects sensitivity to dexamethasone by analyzing HPA axis genes expression in C57Bl/6 mice. Adult male mice were subjected to 30 days of stress, followed by dexamethasone or saline administration. Genes expression was analyzed in the hypothalamus, prefrontal cortex (PFC; <em>Nr3c1</em> only), and adrenal glands at multiple time points post-treatment. CSDS induced marked dysregulation of HPA axis-related genes, including a decrease in hypothalamic <em>Crh</em> and <em>Crhbp</em>, and adrenal <em>Mc2r, Nr3c1</em>, alongside an upregulation of steroidogenic enzymes <em>Cyp11a1</em> and <em>Cyp11b1</em>, which may account for the elevated corticosterone levels observed under chronic stress conditions. CSDS alters the genes expression response to dexamethasone, indicating a delayed recovery of glucocorticoid receptor signaling in the brain and adrenal glands. Our findings reveal significant stress-induced alterations in the expression of key HPA axis genes, suggesting impaired glucocorticoid receptor signaling and potential glucocorticoid resistance in stressed mice.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 116000"},"PeriodicalIF":2.3,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780107","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":"Inferring agency: A two-stage process from early integration to late differentiation during action-outcome monitoring","authors":"Yunyun Chen ,&nbsp;Xintong Zou ,&nbsp;Jianxin Zhao ,&nbsp;Xuemin Zhang","doi":"10.1016/j.bbr.2025.115999","DOIUrl":"10.1016/j.bbr.2025.115999","url":null,"abstract":"<div><div>Inferring agency—the experience of controlling one’s own actions and their consequences—often relies on integrating cues from multiple sources, and recent studies have highlighted the importance of considering the temporal dynamics of this integration process. While previous research has examined how the presence or absence of agency (i.e., reliable versus unreliable sensorimotor cues) affects the neural processing of action-outcomes, it remains unclear whether sensorimotor cues influence this processing dynamically or statically, and how these neural changes relate to explicit judgments of agency. In the present study, participants performed a task in which they moved a ball to a target position under varying motion fluency conditions and then received social feedback regarding their performance, followed by an agency judgement task. Electroencephalography was recorded to capture neural responses during feedback processing. Analyses revealed a dynamic interaction between motion fluency and feedback valence on both the feedback-related negativity (FRN) and explicit agency ratings. Under disfluent motion, the influence of social feedback on both neural responses and agency ratings intensified over time. In contrast, under fluent motion, the influence of social feedback diminished over time. Additionally, FRN was associated with the integration of fluency and feedback, whereas the later P3 component was primarily associated with the influence of fluency on agency ratings. These results indicated that the reflective agency during outcome monitoring could involve an early integration and later differentiation of cues, with the early phase integrating both the sensorimotor and external cues, and the later phase focusing on a more in-depth processing of sensorimotor cues.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 115999"},"PeriodicalIF":2.3,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767028","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":"Vitamin D3 supplementation reverses aging-related changes in cholinergic functions and improves spatial memory in aged rats","authors":"Elif Aksoz ,&nbsp;Medine Karabulut ,&nbsp;Mustafa Hilmi Yaranoğlu","doi":"10.1016/j.bbr.2025.115998","DOIUrl":"10.1016/j.bbr.2025.115998","url":null,"abstract":"<div><h3>Aim</h3><div>Dietary intake and synthesis of vitamin D synthesis decline with age, increasing the risk of vitamin D deficiency. Dementia and Alzheimer's disease development are closely linked to vitamin D deficiency. In this study, we investigated whether vitamin D supplementation could attenuate age-related effects on memory and the hippocampal cholinergic system in aged rats.</div></div><div><h3>Method</h3><div>Thirty Wistar albino male rats (young: 4–5 months old, aged: 21–22 months old) were included in this study. Animals were divided into three groups: The Young control and the Aged control groups were administered physiological serum and the Aged + Vitamin D group was administered vitamin D (500 IU/kg/day). Spatial memory was assessed with the Morris Water Maze test. Then, ACh level and ChAT, AChE, and BChE enzyme activities in the hippocampus were examined.</div></div><div><h3>Results</h3><div>Vitamin D supplementation given to aged rats increased the AchE and BuChE enzyme activities and ACh levels which decreased with aging. The activity of the ChAT enzyme did not change in the aged group, and vitamin D supplementation did not affect it. Increased hippocampal cholinergic transmission improved the spatial memory of aged rats in the MWM test.</div></div><div><h3>Conclusion</h3><div>Vitamin D supplementation improved spatial memory in rats, probably by reversing the aging-related changes in brain cholinergic functions. Vitamin D shows promise in delaying cognitive decline associated with aging and AD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 115998"},"PeriodicalIF":2.3,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767103","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":"Enhancement of cognitive behavior and hippocampal neural oscillations by rhythmic unipolar pulsed magnetic stimulation in 5xFAD Alzheimer's disease mice","authors":"Xuting Wang ,&nbsp;Xue Wang ,&nbsp;Chuncheng Zhao ,&nbsp;Haoyu Zhao ,&nbsp;Pingping Wang ,&nbsp;Tao Song","doi":"10.1016/j.bbr.2025.115995","DOIUrl":"10.1016/j.bbr.2025.115995","url":null,"abstract":"<div><div>Alzheimer's disease (AD) imposes a heavy burden on families and society. Rhythmic magnetic stimulation has emerged as a promising non-invasive therapy to mitigate AD-related cognitive decline. In this study, we applied a rhythmic unipolar compound pulsed magnetic field (cPMF; carrier frequency: 40 Hz, repetition rate: 5 Hz, magnetic flux density: 0–20 mT) incorporating both theta and gamma rhythms to evaluate its effects on behavior and neural oscillations in AD mice and to explore the underlying mechanisms. 5xFAD mice received unipolar cPMF stimulation for 1 h/d over 8 consecutive weeks. Learning and memory were assessed using the novel object recognition (NOR) and the Morris water maze (MWM) tests. In NOR test, unipolar cPMF-treated mice showed a higher cognitive index in test phase 2, and in MWM test, exhibited shorter escape latencies in the training trial and spent less time to first cross the precise former platform location with a higher crossing frequency over this target area in the probe trial. Local field potentials (LFPs) in the hippocampal CA1 area were recorded via <em>in vivo</em> electrophysiology. LFP analysis showed that unipolar cPMF treatment enhanced power of cognitive-related neural oscillations and strengthened theta-gamma phase-amplitude coupling. RNA sequencing analysis further indicated that unipolar cPMF-treated mice exhibited differential gene expression in molecular function and multiple neurotransmitter synaptic signaling pathways. In conclusion, unipolar cPMF might improve cognitive function in 5xFAD mice by modulating cognitive-related neural oscillations. These findings could provide experimental support for the low-intensity pulsed magnetic stimulation as a potential therapeutic strategy for AD.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"500 ","pages":"Article 115995"},"PeriodicalIF":2.3,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761986","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":"Beyond the undermining effect: Extrinsic rewards preserve neural intrinsic reward","authors":"Hiroaki Ayabe ,&nbsp;Takahiko Koike ,&nbsp;Ayumi Yoshioka ,&nbsp;Satoshi Izuno ,&nbsp;Kanae Ogasawara ,&nbsp;Shohei Tsuchimoto ,&nbsp;Norihiro Sadato","doi":"10.1016/j.bbr.2025.115996","DOIUrl":"10.1016/j.bbr.2025.115996","url":null,"abstract":"<div><div>The Self-Determination Theory posits that extrinsic reward withdrawal often undermines intrinsic motivation. This undermining effect varies according to the reward category (e.g., monetary vs. praise). However, the mechanism underlying this variability remains unclear, partly because previous studies have conceptualized intrinsic motivation as a single construct without distinguishing <em>liking</em> (intrinsic value) from <em>wanting</em> (motivational drive). Failure to make this distinction may obscure the effects of rewards on each component. We hypothesized that extrinsic reward withdrawal would differentially affect intrinsic value and motivational drive. To test this hypothesis, we conducted functional magnetic resonance imaging (fMRI) on 54 participants who were randomly assigned to one of three conditions: control (no rewards), monetary reward, or social reward. Participants in the monetary and social reward groups played a stopwatch game twice, first with and then without extrinsic rewards. The control group received no extrinsic rewards during the task. We assessed intrinsic value through fMRI-measured activation of the reward system and motivational drive through voluntary engagement during the task intermission. Intrinsic value, measured by activation in predefined reward-related regions, declined in the control group but was preserved in both extrinsic reward groups after withdrawal. Thus, both monetary and social rewards were associated with preserved intrinsic value. However, intrinsic behavioral motivation declined in the monetary group but was maintained in the social group. These findings suggest that extrinsic reward withdrawal differentially influences intrinsic value and motivational drive across reward categories, thereby clarifying the variability of the undermining effect.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"501 ","pages":"Article 115996"},"PeriodicalIF":2.3,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762007","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}