Psychopharmacology最新文献

{"title":"The nitric oxide synthase inhibitor 7-nitroindazole attenuates social withdrawal and memory impairments induced by Blockade of the NMDA receptor in the rat.","authors":"Angeliki Metaxia Styla, Elias Begas, Nikolaos Pitsikas","doi":"10.1007/s00213-025-06979-5","DOIUrl":"10.1007/s00213-025-06979-5","url":null,"abstract":"<p><strong>Rationale: </strong>That exaggerated production of the gaseous molecule nitric oxide (NO) is associated with the pathogenesis of schizophrenia is well-documented. Therefore, compounds that can adjust nitrergic activity such as NO synthase (NOS) inhibitors might be useful for the treatment of schizophrenia.</p><p><strong>Objectives: </strong>The purpose of the current study was to investigate in the rat the ability of the neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI) in counteracting schizophrenia-like-deficits caused by blockade of the N-methyl-D-aspartate (NMDA) receptor.</p><p><strong>Methods: </strong>7NI's capacity to attenuate social withdrawal, disruption of emotional and recognition memory induced by NMDA receptor antagonists, namely ketamine and MK-801, were evaluated using the social interaction, the step-through passive avoidance, the object recognition and the object location tests. The efficacy of the joint administration of sub-threshold doses of 7-NI with those of the atypical neuroleptics clozapine and risperidone in attenuating recognition memory deficits induced by ketamine was also tested.</p><p><strong>Results: </strong>7-NI (1 and 3 mg/kg) alleviated social withdrawal caused by ketamine (8 mg/kg), abolished emotional memory impairments caused by MK-801 (0.1 mg/kg) and counteracted ketamine (3 mg/kg)-induced recognition memory deficits. Finally, co-administration of inactive doses of 7-NI (0.1 mg/kg) with those of clozapine (0.1 mg/kg) or risperidone (0.03 mg/kg) reduced the detrimental effects of ketamine (3 mg/kg) on recognition memory.</p><p><strong>Conclusions: </strong>The present results indicate that 7-NI is sensitive to glutamate blockade since it decreased behavioural impairments resembling the negative symptoms and cognitive deficits of schizophrenia. Moreover, these findings corroborate the potential of 7-NI as an adjunctive molecule for the medication of schizophrenia.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2321-2338"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting alcohol consumption and reward sensitivity using responses for natural sucrose reward in non-food-restricted rats.","authors":"Erika Shultz, Kristina Thompson, Howard Casey Cromwell","doi":"10.1007/s00213-025-06997-3","DOIUrl":"10.1007/s00213-025-06997-3","url":null,"abstract":"<p><strong>Rationale: </strong>While around 50% of the risk for developing Alcohol Use Disorder (AUD) has been determined to be genetic, examining predictors of addictive-like behavior and individual variance in models without a family history of addiction is also important. Impaired reward sensitivity and response to natural reward may play a role in an individual's propensity to develop alcohol addiction. Little research has been done on predictors of alcohol addiction without food or water deprivation to coax animals into addiction.</p><p><strong>Objectives: </strong>This study seeks to examine psychological and behavioral predictors of alcohol addiction in non-food restricted rats and determine whether sucrose seeking, consumption, and reward sensitivity relates to later motivation and reward-sensitivity related functions for ethanol.</p><p><strong>Methods: </strong>This study examined the appetitive and consummatory behavior of female Wistar rats in self-administration tasks using sucrose and ethanol solutions and ad-libitum access to food and water. Varying time of access for sucrose was utilized to evaluate reward sensitivity analyzing inter-session and intra-session measures.</p><p><strong>Results: </strong>Operant sucrose consumption predicted both 15% and 30% ethanol consumption in the home cage during 30-min exposure. Animals expressed key differences in reward sensitivity between natural and drug reward including lack of reward discrimination for sucrose during consumption along with different profiles of responding for sucrose and ethanol during the anticipatory motivated actions.</p><p><strong>Conclusions: </strong>Using more precise measures of natural reward sensitivity could provide key insight into vulnerability to develop substance use disorders.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2445-2462"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic cannabis use is associated with alterations in resting-state cerebellar-cortical connectivity.","authors":"Ilenia Salsano, Giorgia Picci, Nathan M Petro, Anna T Coutant, Lucy K Horne, Jason A John, Ryan Glesinger, Gaelle Doucet, Tony W Wilson","doi":"10.1007/s00213-025-06981-x","DOIUrl":"10.1007/s00213-025-06981-x","url":null,"abstract":"<p><strong>Rationale: </strong>Cannabis is one of the most widely used psychoactive drugs in the United States, yet its long-term effects on brain function remain poorly understood. Prior resting-state functional connectivity (rsFC) studies have yielded inconsistent findings, likely due to variability in cannabis use thresholds, a predominant focus on younger populations, and region-of-interest (ROI)-based approaches limited to a small number of a priori brain regions.</p><p><strong>Objectives: </strong>We aimed to address these limitations by examining rsFC across the entire brain using an atlas-based, whole-brain, ROI-to-ROI approach in a middle-aged sample (mean age = 41.64 years) of individuals with chronic cannabis use (CCU) and a demographically matched group of controls who did not use cannabis or other illicit substances. Based on the known neuroanatomical distribution of type 1 cannabinoid receptors (CB1Rs), we hypothesized that regions with high CB1R density would be the most affected. However, given our whole-brain approach, we were also sensitive to other regions that may exhibit altered connectivity.</p><p><strong>Methods: </strong>Using the Automated Anatomical Labeling (AAL) atlas, we computed rsFC matrices across 116 brain regions in 22 adults with CCU and 23 demographically matched controls.</p><p><strong>Results: </strong>The CCU group showed decreased rsFC (p_FDR< .05) between the right cerebellar Crus II and the left pars triangularis, bilateral pars orbitalis, left superior frontal gyrus, left middle temporal gyrus, and left inferior temporal gyrus compared with the control group. The CCU group also had lower rsFC (p_FDR < .05) between the right cerebellar Crus I and the left pars triangularis compared with controls.</p><p><strong>Conclusions: </strong>Our findings revealed disrupted rsFC between cerebellar and prefrontal-temporal regions in the CCU group. This study advances the literature by using an atlas-based, whole-brain, ROI-to-ROI approach in a middle-aged sample with sustained cannabis use. Future studies should integrate neuropsychological assessments and task-based paradigms to understand how such alterations in rsFC affect behavioral outcomes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2339-2350"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing prenatal valproic acid exposure in zebra finches to model autism-related phenotypes.","authors":"Ákos Pogány, Estifanos Ghebrihiwet Tewelde, Boglárka Morvai, Gergely Zachar","doi":"10.1007/s00213-025-06975-9","DOIUrl":"10.1007/s00213-025-06975-9","url":null,"abstract":"<p><strong>Rationale: </strong>Rodent models dominate autism spectrum disorder (ASD) research, yet their translational validity is limited for a heterogeneous condition with complex social-vocal phenotypes.</p><p><strong>Objectives: </strong>To evaluate the zebra finch (Taeniopygia guttata) - a highly social, vocal-learning songbird - as an ASD model by adapting embryonic valproic acid (VPA) exposure and identifying dose-timing conditions that preserve viability while perturbing social behavior.</p><p><strong>Methods: </strong>We used a 3 × 3 design crossing VPA dose (0, 0.3, 0.6 µmol/egg) with manipulation day (incubation days 8-10). Hatching success, post-hatching survival, growth, and social behavior in a bird-adapted three-chamber test were quantified with mixed-effects models (binomial/Cox/linear/negative binomial, beta-binomial).</p><p><strong>Results: </strong>Hatching success decreased at 0.6 µmol and with day-8 injections; day-9 performed best. Post-hatching survival was lower at 0.3 µmol versus controls (limited inference for 0.6 µmol due to small n). Growth showed dose×sex interactions: females at 0.6 µmol were lighter with shorter tarsi; wings showed a similar tendency. In sociability (phase 1), time-based measures were unchanged, 0.6-µmol birds made more approaches to the closest perch, while day-8 birds approached less than day-9. In phase 2, time on the familiar-side closest perch showed a day×sex interaction (day-8 females spent less time than day-8 males), and approaches to that perch increased at 0.6 µmol. Overall sociability (combined closest perches) and total activity did not differ by group.</p><p><strong>Conclusions: </strong>Embryonic VPA in zebra finches yields selective, partly sex-dependent developmental and social effects. Zebra finches remain promising; day-9 intermediate doses (~ 0.35-0.50 µmol) warrant follow-up to map dose-response and balance viability with behavioral detectability.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2249-2265"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145638015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on pharmacogenomic approaches in the treatment of autism spectrum disorders.","authors":"Komal Thapa, Heena Khan, Neha Kanojia, Jatin Kumar, Thakur Gurjeet Singh, Amarjot Kaur Grewal","doi":"10.1007/s00213-026-07020-z","DOIUrl":"10.1007/s00213-026-07020-z","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2237-2248"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A classic traditional chinese medicine formula for depression: mechanistic insights from phytochemical constituents and multitarget pathways.","authors":"Sijia Wang, Yi Zhao, Jin Pan, Dongmei Zhang, Aicheng Wang, Ke Ma","doi":"10.1007/s00213-025-06978-6","DOIUrl":"10.1007/s00213-025-06978-6","url":null,"abstract":"<p><strong>Rationale: </strong>Depression is a common mood disorder that seriously affects the quality of life and working ability of patients. Zhi-Zi-Hou-Po Decoction (ZZHPD), a classical formula from the Traditional Chinese Medicine (TCM), is widely used to treat depression. Although ZZHPD exhibits potent antidepressant effects, its specific mechanism of action and active ingredients remain unknown.</p><p><strong>Objectives: </strong>This article focused on identifying and analysing the major phytochemical in ZZHPD that exhibit antidepressant effects. It also provided theoretical data for the standardized clinical application of ZZHPD.</p><p><strong>Methods: </strong>A systematic review of the materia medica, chemical composition, and pharmacological effects from multi-source literature databases to elucidate the antidepressant mechanism of ZZHPD. And further validation was performed using a comprehensive bioinformatics analysis of network pharmacology and molecular docking.</p><p><strong>Results: </strong>The antidepressant effect of ZZHPD is achieved through multiple pathways and targets. The key phytochemical constituents of ZZHPD include 3 categories, iridoids, flavonoids, and lignans, which are specifically included geniposide, magnolol, honokiol, hesperidin, hesperetin, naringin, naringenin, nobiletin, and 3,5,6,7,8,3',4'-heptamethphoxyflavone (HMF). The main antidepressant mechanisms include enhancing monoaminergic system function, inhibiting neuroinflammation, restoring HPA axis negative feedback, enabling neurogenesis and neuroplasticity, neuroprotective effects, inhibition of neuronal apoptosis and pyroptosis, antioxidative stress, and regulation of noncoding RNA.</p><p><strong>Conclusions: </strong>In summary, ZZHPD demonstrates antidepressant effects through multi-component, multi-target, and multi-pathway mechanisms. It shows promise for treating depression at the molecular, cellular, and systemic levels, with significant clinical application value.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2291-2320"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145637997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing behavioural economic demand for morphine after an acute dose in individuals with- and without childhood trauma: a double-blind, randomised, controlled trial.","authors":"Martin Trøstheim, Benjamin L Berey, Elizabeth R Aston, Matthew J Gullo, Lee Hogarth, Graham Simpson, Rupert Broomby, Celia J Morgan, Molly Carlyle","doi":"10.1007/s00213-025-06977-7","DOIUrl":"10.1007/s00213-025-06977-7","url":null,"abstract":"<p><strong>Background: </strong>Childhood trauma is associated with positive subjective responses to acute opioids in the laboratory. Yet, its impact on behavioural economic demand for opioids remains unclear. Because demand can predict future use and misuse, we investigated whether individuals with childhood trauma also display greater demand for opioids in the laboratory.</p><p><strong>Methods: </strong>This secondary analysis used data from a double-blind, randomised, controlled, counterbalanced trial. Across two sessions, individuals with (n = 26) and without (n = 21) childhood trauma received a high (0.15 mg/kg) and low (0.01 mg/kg) dose of intramuscular morphine 120 min before a hypothetical purchase task. Participants also regularly reported their subjective desire for the study drug. Area under the consumption and expenditure curves, and specific demand indices (O_max, P_max, breakpoint, intensity, elasticity), were analysed with non-parametric mixed models.</p><p><strong>Results: </strong>Consumption and expenditure for low dose morphine was lower in the childhood trauma group when compared to high dose morphine in this group, and low dose morphine in the control group (ps ≤ 0.03). Consistent results were obtained for specific demand indices O_max, P_max, and breakpoint, but not intensity or elasticity. Positive correlations between subjective desire and consumption and expenditure were only observed in the childhood trauma group (Tau-c = 0.24-0.34, ps ≤ 0.03).</p><p><strong>Conclusion: </strong>Under laboratory conditions, desires to use opioids among individuals with childhood traumas may not manifest in strong intentions to acquire these drugs. Diverging results from psychometric measures of subjective and economic opioid value highlight the need for future research to explore contextual and resilience factors to understand how problematic opioid use emerges after childhood traumas.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2277-2290"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12942358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of morphine self-administration on brain structure and microglial phenotypic diversity in the absence of neuronal loss in male Wistar rats.","authors":"Ana Débora Elizarrarás-Herrera, David Medina-Sánchez, Mariana Stefania Serrano-Ramírez, Diego Angeles-Valdez, Luis A Trujillo-Villarreal, María Antonieta Carbajo-Mata, César J Carranza-Aguilar, Eduardo A Garza-Villarreal","doi":"10.1007/s00213-025-06994-6","DOIUrl":"10.1007/s00213-025-06994-6","url":null,"abstract":"<p><strong>Rationale: </strong>Opioid addiction, including morphine use, is a major public health crisis in the U.S. It has been associated with brain volume changes in reward-related regions, neuronal loss, and neuroinflammation. While these alterations have been studied separately, it remains unclear whether structural changes co-occur with microglial adaptations at early stages of morphine use.</p><p><strong>Objective: </strong>This study aimed to examine region-specific brain volume changes, cellular counts, and the emergence of distinct microglial phenotypes in addiction-related regions, using a model of morphine self-administration that simulates the early phase of morphine consumption.</p><p><strong>Methods: </strong>Male Wistar rats were trained to self-administer morphine (0.01 mg/kg/inf) for 20 days in 3-hour daily sessions under operant conditioning. Structural MRI was conducted before and after the self-administration period, and brain volume was quantified using deformation-based morphometry. Brain tissue was immunolabeled for Iba1 and NeuN, and confocal microscopy images of microglia were analyzed using principal component analysis and K-means clustering.</p><p><strong>Results: </strong>Morphine self-administration produced volume increases in the globus pallidus and reductions in the insular cortex. Microglial density was elevated in these regions and other addiction-related areas, including the caudate-putamen and dentate gyrus, without significant variations in neuronal count but with a marked reduction in neuronal soma size in these latter regions. Clustering revealed diverse microglial phenotypes, including intermediate morphologies, with region-dependent distributions indicative of diverse neuroinflammatory states.</p><p><strong>Conclusions: </strong>These findings suggest that morphine-induced brain volume changes during the early stages of consumption are not attributable to neuronal loss but may reflect adaptive processes involving neuronal restructuring and microglial remodeling. Microglial phenotyping emerges as a sensitive approach for detecting neuroinflammatory patterns linked to addiction vulnerability.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2411-2427"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spike-wave discharges are uncoupled with cognitive outcome in aged Long-Evans rats.","authors":"Craig Myrum, Zach Uttke, Diba Ramezan, Margaret E Stelzner, Jeffrey M Long, Peter R Rapp","doi":"10.1007/s00213-025-06976-8","DOIUrl":"10.1007/s00213-025-06976-8","url":null,"abstract":"<p><strong>Rational: </strong>Rodent EEGs display 7-12 Hz oscillations called spike-wave discharges (SWDs) that are more abundant with age, and some data suggest that they might interfere with hippocampus-dependent memory processing.</p><p><strong>Objective: </strong>To test whether SWD activity contributes to the memory decline reported in aged rats.</p><p><strong>Methods: </strong>Spatial learning was assessed in young and aged Long-Evans (LE) rats using a water maze protocol where aged rats display substantial interindividual variability in hippocampus-dependent memory. We then collected 24 h EEG data to quantify SWD incidence and duration among young and aged animals. Lastly, we took a pharmacological approach to test the efficacy of two antiepileptic drugs-levetiracetam and ethosuximide-at reducing SWD activity.</p><p><strong>Results: </strong>We found that SWDs were significantly more frequent in aged rats than young, but entirely unrelated to between-subject differences in cognitive outcome. Age-dependent increases in SWD frequency were also insensitive to levetiracetam at doses known to reverse memory impairment in aged rats, but potently inhibited by the other antiepileptic drug, ethosuximide, that functions through a different mechanism of action.</p><p><strong>Conclusion: </strong>Together these findings provide evidence that the disrupted excitatory/inhibitory balance associated with individual differences in cognitive aging is unrelated to the SWD increase seen in aged rats.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2267-2276"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal hypoactivity correlates with immediate extinction deficit following Pavlovian fear conditioning with a chasing threat.","authors":"Kyeong Im Jo, Ji Hoon Jeong, June-Seek Choi","doi":"10.1007/s00213-025-06991-9","DOIUrl":"10.1007/s00213-025-06991-9","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2369-2377"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}