Neuropsychopharmacology最新文献

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VTA-ACC dopaminergic circuit mediates trait anxiety-related observational learning of social avoidance in male mice VTA-ACC多巴胺能回路介导雄性小鼠特质焦虑相关的社交回避观察性学习。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-06-12 DOI: 10.1038/s41386-025-02139-7
Ming Li, Kun Ren, Chi Cui, Yulong Shi, Jie Lei, Tongxia Li, Jian Yang, Xiang Peng, Xueke Yang, Yibo Yao, Gangan Luo, Junsong Du, Sitong Chen, Pei Zhang, Bo Tian
{"title":"VTA-ACC dopaminergic circuit mediates trait anxiety-related observational learning of social avoidance in male mice","authors":"Ming Li, Kun Ren, Chi Cui, Yulong Shi, Jie Lei, Tongxia Li, Jian Yang, Xiang Peng, Xueke Yang, Yibo Yao, Gangan Luo, Junsong Du, Sitong Chen, Pei Zhang, Bo Tian","doi":"10.1038/s41386-025-02139-7","DOIUrl":"10.1038/s41386-025-02139-7","url":null,"abstract":"Social animals encounter both environmental and social stress, yet the mechanisms by which individuals with different levels of trait anxiety cope with these stressors, as well as the neurobiological links between trait anxiety and social cognition, remain incompletely understood. Here, male mice are classified into high-trait anxiety (HTA) and low-trait anxiety (LTA) groups based on their anxiety responses to elevated platform exposure in the open field test. Under observational learning-based vicarious social defeat stress (VSDS), HTA mice exhibit less social avoidance behavior toward CD1 aggressors than LTA mice. Fiber photometry reveals that HTA mice display higher activity of ventral tegmental area (VTA) dopaminergic (VTADA) neurons during environmental stress, while LTA mice exhibit greater VTADA neurons activity under social stress. Viral tracing identifies the connectivity of VTADA neurons and anterior cingulate cortex (ACC). Optogenetic and chemogenetic manipulations demonstrate that VTA-ACC dopaminergic circuit is necessary and sufficient for VSDS-induced social avoidance behavior in HTA and LTA mice. RNA-sequencing suggested that VTA neuroinflammatory signaling may be a key factor contributing to the difference between HTA and LTA mice. Thus, this study reveals a neural circuit mechanism for trait anxiety-related observational learning of social avoidance behavior in male mice, and provides a molecular mechanism in shaping trait anxiety.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1364-1375"},"PeriodicalIF":6.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Merkel cell stimulation in fear and sensory signaling 默克尔细胞刺激恐惧和感觉信号。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-06-07 DOI: 10.1038/s41386-025-02144-w
Austin C. Korgan, Rodrigo Orso, Isabelle J. Sibley, Kathryn E. Prendergast, Tanja Jovanovic, Tracy L. Bale
{"title":"Merkel cell stimulation in fear and sensory signaling","authors":"Austin C. Korgan, Rodrigo Orso, Isabelle J. Sibley, Kathryn E. Prendergast, Tanja Jovanovic, Tracy L. Bale","doi":"10.1038/s41386-025-02144-w","DOIUrl":"10.1038/s41386-025-02144-w","url":null,"abstract":"Stress and traumatic experiences have significant and lasting effects on sensory systems. We recently identified unique expression of proteins associated with epidermal skin cells (keratinocytes) and mechanosensory Merkel cells (MC) in circulating extracellular vesicles from adult women who had experienced sexual trauma specifically during adolescence, biologically linking trauma exposure with a specific neuron-like skin cell. Here, we aimed to develop and validate a preclinical mouse model utilizing chemogenetic (DREADD Gq) activation of a population of MC. Using a reporter line, we confirmed the expected pattern of the Krt14 Cre in specific MC skin areas and that these tissues expressed relevant MC marker genes similarly between male and female mice. Chemogenetic stimulation of MC produced robust neuronal activation of the insular cortex (IC), a brain region relevant to somatosensory and valence integration. To determine if the mice could detect MC activation, home cage behaviors following CNO treatment significantly increased nest grooming time. Conditioned place preference further revealed an avoidance response following MC stimulation; an effect that was stronger in female mice. Finally, to connect back to our trauma question, we examined MC activation in fear conditioning and identified deficits in fear extinction. Overall, these studies validate utilization of this preclinical model in further investigating the mechanosensory system and its potential involvement in PTSD symptoms and therapeutic interventions. Ongoing studies will focus on critical developmental periods relevant to both MC development and sex differences associated with trauma vulnerability and potential sensory based therapeutic options for PTSD-related symptoms.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1395-1405"},"PeriodicalIF":6.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02144-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
One step at a time: use of single-session rTMS to test novel targets for substance use disorders 一步一步:使用单次rTMS测试物质使用障碍的新目标。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-06-06 DOI: 10.1038/s41386-025-02149-5
Heather Burrell Ward
{"title":"One step at a time: use of single-session rTMS to test novel targets for substance use disorders","authors":"Heather Burrell Ward","doi":"10.1038/s41386-025-02149-5","DOIUrl":"10.1038/s41386-025-02149-5","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1317-1318"},"PeriodicalIF":6.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02149-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NAc-DBS selectively enhances memory updating without effect on retrieval NAc-DBS选择性地增强记忆更新,但不影响检索。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-05-27 DOI: 10.1038/s41386-025-02132-0
Andrés Pérez-Segura, Jorge Medina, Antonio Cerdán Cerdá, Cristina Sánchez-Ferri, Daniel Torres, Claudio R. Mirasso, Bryan Strange, Víctor M. Eguíluz, Lucas Lacasa, Santiago Canals
{"title":"NAc-DBS selectively enhances memory updating without effect on retrieval","authors":"Andrés Pérez-Segura, Jorge Medina, Antonio Cerdán Cerdá, Cristina Sánchez-Ferri, Daniel Torres, Claudio R. Mirasso, Bryan Strange, Víctor M. Eguíluz, Lucas Lacasa, Santiago Canals","doi":"10.1038/s41386-025-02132-0","DOIUrl":"10.1038/s41386-025-02132-0","url":null,"abstract":"Deep brain stimulation (DBS) has emerged as a widely used therapeutic option when pharmacological treatments prove ineffective or refractory for psychiatric patients. The nucleus accumbens (NAc) represents a frequently targeted site in DBS interventions due to its demonstrated safety profile and therapeutic efficacy in obsessive-compulsive disorder, major depression, and anorexia nervosa. However, limited mechanistic understanding hampers its broader clinical applicability. This study sought to delineate the distinct behavioural dimensions modulated by NAc-DBS, its impact on distinct facets of memory, and to elucidate the underlying brain-network mechanism of action. We developed a novel spatial navigation task for rats and employed a high-dimensional behavioural analysis complemented by fMRI to dissect the cognitive, behavioural and neurobiological effects of NAc-DBS. Active NAc-DBS in male rats produced a selective enhancement of long-term memory encoding without affecting memory recall or working memory. We found a small but statistically significant rewarding effect of NAc-DBS, with no detectable impact on motor or stress-related behaviours. Sustained neuronal activation in the NAc, septum, entorhinal and insular cortex demonstrated no desensitisation to chronic NAc-DBS, which triggered a functional reorganisation among dopaminergic-related structures. These findings suggest that NAc-DBS induces a functional reorganisation in the mesocorticolimbic system, potentially mimicking a dopaminergic novelty signal to enhance memory updating. This provides a mechanistic basis for the therapeutic use of NAc-DBS, particularly in improving cognitive flexibility in psychiatric disorders.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1420-1429"},"PeriodicalIF":6.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02132-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cortical myelin mapping in antipsychotic medication-naïve, first-episode psychosis patients 抗精神病药medication-naïve首发精神病患者的皮质髓鞘定位。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-05-23 DOI: 10.1038/s41386-025-02137-9
Victoria L. King, Gerhard Hellemann, Adrienne C. Lahti, Matthew Defenderfer, Jill R. Glausier, Hui Zhang, Nina V. Kraguljac
{"title":"Cortical myelin mapping in antipsychotic medication-naïve, first-episode psychosis patients","authors":"Victoria L. King, Gerhard Hellemann, Adrienne C. Lahti, Matthew Defenderfer, Jill R. Glausier, Hui Zhang, Nina V. Kraguljac","doi":"10.1038/s41386-025-02137-9","DOIUrl":"10.1038/s41386-025-02137-9","url":null,"abstract":"While white matter myelin primarily functions to accelerate conduction velocity and has been extensively studied in schizophrenia-spectrum disorders (SSD), less is known about the role of gray matter myelin in SSD. Cortical myelination occurs mostly on the proximal axons of parvalbumin positive (PV+) interneurons, where it assists in trophic support and experience-dependent plasticity. Given the role of PV+ interneuron dysfunction in SSD, it is critical to advance our understanding of cortical myelin pathology in this context. Here, we quantified myelin maps using the T1w/T2w ratio in a large group of antipsychotic medication-naïve, first-episode psychosis patients. We compared myelin content between patients (N = 91) and controls (N = 107) using a MANCOVA and calculated zero-order correlations with the discriminant function for each region, then used a machine learning approach to identify the most parsimonious constellation of cortical regions driving group differences using a stepwise algorithm. Group membership was significantly associated with T1w/T2w ratio (Wilks Lambda = 0.09, p < 0.01), where patients had higher myelin values compared to healthy controls. We identified a subset of 16 regions, primarily located in association cortices, that were sufficient to explain group differences. Here, we report an increase in the cortical T1w/T2w ratio in association cortices in first-episode psychosis. We suggest that faulty myelin compaction during this critical developmental period could contribute to PV+ interneuron pathology and cortical microcircuit disruptions resulting in the clinical phenotype. With additional empirical support from future studies, novel treatment strategies targeting cortical myelin could have potential to mitigate circuit dysfunction in the illness.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1439-1445"},"PeriodicalIF":6.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02137-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Tailtag: A multi-mouse tracking system to measure social dynamics in complex environments 尾标:一个多鼠标跟踪系统,用于测量复杂环境中的社会动态。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-05-22 DOI: 10.1038/s41386-025-02126-y
Vincent Coulombe, Arturo Marroquin Rivera, Sadegh Monfared, David-Alexandre Roussel, Quentin Leboulleux, Modesto R. Peralta III, Benoit Gosselin, Benoit Labonté
{"title":"The Tailtag: A multi-mouse tracking system to measure social dynamics in complex environments","authors":"Vincent Coulombe, Arturo Marroquin Rivera, Sadegh Monfared, David-Alexandre Roussel, Quentin Leboulleux, Modesto R. Peralta III, Benoit Gosselin, Benoit Labonté","doi":"10.1038/s41386-025-02126-y","DOIUrl":"10.1038/s41386-025-02126-y","url":null,"abstract":"Despite recent advances, tracking individual movements safely and reliably over extended periods, particularly within complex social groups, remains a challenge. Traditional methods like color coding, tagging, and RFID tracking, while effective, have notable practical limitations. State-of-the-art neural network-based trackers often struggle to maintain individual identities in large groups for more than a few seconds. Fiducial tags such as ArUco codes present a potential solution to enable accurate tracking and identity management. However, their application to large groups of socially interacting mice in complex, enriched environments remain an open challenge. Here, we present the Tailtag system, a novel approach designed to address this challenge. The Tailtag is a non-invasive, safe, and ergonomic tail ring embedded with an ArUco marker allowing to track individual mice in colonies of up to 20 individuals in complex environments for at least seven days without performance degradation or behavioral alteration. We provide a comprehensive parameter optimization guide and practical recommendations for marker selection, for reproducibility across diverse experimental setups. Using data collected from Tailtag-equipped mice, we revealed the formation and evolution of social groups within the colony. Our analysis identified social hub regions within the vivarium where social contacts occur at different frequencies throughout one week of recordings. We quantified interactions and avoidance patterns between specific pairs of mice within the most active social hubs. Overall, our findings indicate that while the zone preferences and peer associations among the mice change over time, certain groups and pairwise interactions consistently form within the social colony.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1336-1345"},"PeriodicalIF":6.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41386-025-02126-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stress-related genetic factors modify the effect of socioeconomic status on cardiovascular risk 与压力相关的遗传因素改变了社会经济地位对心血管风险的影响。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-05-21 DOI: 10.1038/s41386-025-02130-2
Krystel Abi Karam, Shady Abohashem, Hui Chong Lau, Giovanni Civieri, Wesam Aldosoky, Maria Khalil, Gagandeep Singh Arora, Robert Rollings, Alula Assefa, Taha Z. Ahmad, Jamie W. Bellinge, Azar Radfar, Karmel Choi, Jordan W. Smoller, Antonia V. Seligowski, Ahmed Tawakol, Michael T. Osborne
{"title":"Stress-related genetic factors modify the effect of socioeconomic status on cardiovascular risk","authors":"Krystel Abi Karam, Shady Abohashem, Hui Chong Lau, Giovanni Civieri, Wesam Aldosoky, Maria Khalil, Gagandeep Singh Arora, Robert Rollings, Alula Assefa, Taha Z. Ahmad, Jamie W. Bellinge, Azar Radfar, Karmel Choi, Jordan W. Smoller, Antonia V. Seligowski, Ahmed Tawakol, Michael T. Osborne","doi":"10.1038/s41386-025-02130-2","DOIUrl":"10.1038/s41386-025-02130-2","url":null,"abstract":"Lower socioeconomic status (SES) and higher neuroticism polygenic risk score (NEU-PGS) associate with cardiovascular disease (CVD). Chronic stress increases CVD risk via activation of neural, autonomic, and immune pathways. We evaluated whether 1) higher NEU-PGS accentuates the association between lower SES and major adverse cardiovascular events (MACE); and 2) higher stress-associated neural activity and C-reactive protein and lower heart rate variability contribute to the SES-MACE link among those with higher NEU-PGS. NEU-PGS (from those with European ancestry) and SES data were derived from individuals in the Mass General Brigham Biobank. SES was assessed as median household income (N = 18,093) and area deprivation index (ADI, N = 15,276). Lower household income was defined as the lowest tertile and higher ADI as the highest. NEU-PGS was stratified about the population median. MACE, stress-associated neural activity, heart rate variability, and C-reactive protein were assessed from clinical data. Among individuals with higher (but not lower) NEU-PGS, lower household income associated with MACE (N = 6,574; OR: 1.22, p = 0.005), stress-associated neural activity (N = 480; standardized β: 0.14, p = 0.003), and heart rate variability (1,361; −0.05, p = 0.041). Higher ADI associated with MACE (5,441; 1.24, p = 0.008) and heart rate variability (1,127; −0.09, p = 0.001) among those with higher (but not lower) NEU-PGS. Lower SES associated with higher C-reactive protein across NEU-PGS groups. The mediating effect of stress-associated neural activity, heart rate variability and C-reactive protein in the SES-MACE relationship was moderated by higher NEU-PGS. Individuals with higher NEU-PGS experience greater CVD risk related to lower SES via alterations in neural, autonomic, and immune mechanisms.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1327-1335"},"PeriodicalIF":6.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of NMDA receptor antagonists on working memory and gamma oscillations, and the mediating role of the GluN2D subunit. NMDA受体拮抗剂对工作记忆和γ振荡的影响,以及GluN2D亚基的介导作用。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-05-15 DOI: 10.1038/s41386-025-02129-9
Chitra Vinnakota, Matthew R Hudson, Kazutaka Ikeda, Soichiro Ide, Masayoshi Mishina, Suresh Sundram, Nigel C Jones, Rachel Anne Hill
{"title":"Effects of NMDA receptor antagonists on working memory and gamma oscillations, and the mediating role of the GluN2D subunit.","authors":"Chitra Vinnakota, Matthew R Hudson, Kazutaka Ikeda, Soichiro Ide, Masayoshi Mishina, Suresh Sundram, Nigel C Jones, Rachel Anne Hill","doi":"10.1038/s41386-025-02129-9","DOIUrl":"https://doi.org/10.1038/s41386-025-02129-9","url":null,"abstract":"<p><p>Working memory relies on synchronised network oscillations involving complex interplay between pyramidal cells and GABAergic interneurons. NMDA receptor (NMDAR) antagonists influence both network oscillations and working memory, but the relationship between these two consequences has not been elucidated. This study aimed to determine the effect of NMDAR antagonists on network oscillations during a working memory task in mice, and the contribution of the GluN2D receptor subunit. After training wildtype (WT) and GluN2D-knockout (KO) mice on the Trial-Unique-Non-match to Location (TUNL) touchscreen task of working memory, recording electrodes were implanted into the prefrontal cortex (PFC) and hippocampus. Mice were challenged with either (S)-ketamine (30 mg/kg), (R)-ketamine (30 mg/kg), phencyclidine (PCP, 1 mg/kg), MK-801 (0.3 mg/kg) or saline prior to TUNL testing while simultaneous local field potential recordings were acquired. PCP disrupted working memory accuracy in WT (p = 0.001) but not GluN2D-KO mice (p = 0.79). MK-801 (p < 0.0001), (S)-ketamine (p < 0.0001) and (R)-ketamine (p = 0.007) disrupted working memory accuracy in both genotypes. PCP increased baseline hippocampal gamma (30-80 Hz) power in WT (p = 0.0015) but not GluN2D-KO mice (p = 0.92). All drugs increased baseline gamma power in the PFC in both genotypes (p < 0.05). Low gamma was induced during the maintenance phase of the TUNL task and increased when mice correctly completed the task (p = 0.024). This response-dependent increase in low gamma was disrupted by all drugs. In summary, PCP action involves the GluN2D subunit of the NMDA receptor in the hippocampus to alter baseline gamma power and working memory. Task-induced low gamma activity during maintenance aligns with task performance, and is disrupted by all NMDAR antagonists.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Selective KOR antagonist alters functional patch sizes in individualized brain system: results from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS) 选择性KOR拮抗剂改变个体化脑系统的功能斑块大小:来自情绪和焦虑谱系障碍(FAST-MAS)快速失败试验的结果。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-05-13 DOI: 10.1038/s41386-025-02125-z
Hoki Fung, Ruby M. Potash, Andrew Krystal, Diego A. Pizzagalli, Matthew D. Sacchet
{"title":"Selective KOR antagonist alters functional patch sizes in individualized brain system: results from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS)","authors":"Hoki Fung,&nbsp;Ruby M. Potash,&nbsp;Andrew Krystal,&nbsp;Diego A. Pizzagalli,&nbsp;Matthew D. Sacchet","doi":"10.1038/s41386-025-02125-z","DOIUrl":"10.1038/s41386-025-02125-z","url":null,"abstract":"In our prior study involving a transdiagnostic sample of individuals with anhedonia, we showed that an 8-week administration of a selective κ-opioid receptor (KOR) antagonist enhanced fMRI ventral striatal activation during reward anticipation in the Monetary Incentive Delay task as compared to a placebo. However, individual differences in brain architecture may limit the translation of this finding to the context of precision medicine. Here, we adopted an individual-specific approach to elucidate the effects of selective KOR antagonism on cortical-subcortical reward circuits in individuals with anhedonia. Sixty-four participants with anhedonia (30 KOR Antagonist, 34 Placebo) who completed both pre- and post- treatment MRI scans in the FAST-MAS study were included in this analysis. Using an individualized-brain-systems-functional-brain-mapping approach, functional networks were mapped at the individual level, and individual-specific cortical patches and subcortical-cortical clusters were obtained. Statistical analyses were conducted to examine the pre- and post-treatment changes in patch and cluster sizes, as well as their relationships with clinical-cognitive measures. ROI analyses revealed a significant patch size decrease in the right medial posterior prefrontal cortex within the frontoparietal control network, and significant size increases in three right subcortical clusters – pallidum, amygdala, and thalamus – within the orbitofrontal-limbic network, following KOR antagonist treatment. In short,&nbsp;we applied recently developed computational neuroimaging approaches to examine changes in the individualized brain systems of FAST-MAS participants before and after eight weeks of KOR antagonist treatment for anhedonia. Our results revealed alterations in functional cortical patch and subcortical-cortical cluster sizes in anhedonia-related brain regions following KOR antagonist treatment.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"50 9","pages":"1430-1438"},"PeriodicalIF":6.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Demand for heroin in rats: effects of non-drug alternative substitutes and complements. 大鼠对海洛因的需求:非药物替代品和补品的影响。
IF 6.6 1区 医学
Neuropsychopharmacology Pub Date : 2025-05-09 DOI: 10.1038/s41386-025-02127-x
David N Kearns, Toni Bird, Emma M Pilz, Kevin Chavez-Lopez, Felipe Rego, Alan Silberberg
{"title":"Demand for heroin in rats: effects of non-drug alternative substitutes and complements.","authors":"David N Kearns, Toni Bird, Emma M Pilz, Kevin Chavez-Lopez, Felipe Rego, Alan Silberberg","doi":"10.1038/s41386-025-02127-x","DOIUrl":"10.1038/s41386-025-02127-x","url":null,"abstract":"<p><p>Given the central role of economic demand for drugs in substance use disorder, identifying factors that increase or decrease drug value is of high importance. The present study investigated how the concurrent availability of non-drug reinforcers previously shown to be heroin substitutes or complements affected demand for heroin in rats. In Exp. 1, three groups of rats pressed one lever for intravenous heroin infusions on a series of prices that increased over sessions. The groups differed with respect to what they received for pressing a second lever: timeout-from-avoidance (TOA) reinforcers, heroin at a constant low price, or no programmed consequences. The essential value of heroin was significantly reduced in the groups that had either TOA or low-price heroin available on the second lever. Additionally, as the price of heroin on the first lever increased, consumption of TOA reinforcers or low-price heroin infusions increased, confirming that these were substitutes for expensive heroin. In Exp. 2, two groups of rats pressed one lever for heroin infusions on a series of increasing prices. One group could press a second lever for saccharin reinforcers at a constant low price. Concurrent saccharin availability increased demand for heroin in female rats, but not in male rats. Exp. 3 compared demand for saccharin in groups that had or did not have concurrent access to low-price heroin. Concurrent heroin availability caused an increase in estimated saccharin consumption at no cost (Q<sub>0</sub>), but did not affect elasticity of demand for saccharin. The outcome of Exp. 1 suggests that non-drug means of reducing pain or stress can weaken demand for opioids. Exp. 2 and 3 show that, in contrast, availability of some non-drug alternatives can increase demand for heroin in female rats and that heroin can increase consumption of non-drug alternatives at low price. Overall, these results show, consistent with the contextualized reinforcer pathology model, that opioid value depends on the broader behavioral economic context in which opioids and non-drug alternatives are available.</p>","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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