Psychopharmacology最新文献

{"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683524/pdf/","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":"OA","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683258/pdf/","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":"OA","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}

{"title":"Beyond dopamine: Broader neuromodulatory contributions in sign- and goal-tracking.","authors":"Amber Datta, Arya Datta, Noah Collins, Stephanie L Grella, Ali Gheidi","doi":"10.1007/s00213-026-07013-y","DOIUrl":"10.1007/s00213-026-07013-y","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2223-2235"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348851","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":"Treatment response to bupropion: an investigation of changes in resting-state functional connectivity in patients with major depressive disorder.","authors":"Sandra E Klonteig, Annabel E L Walsh, Rune Jonassen, Michael Browning, Catherine J Harmer, Marieke A G Martens","doi":"10.1007/s00213-025-06993-7","DOIUrl":"10.1007/s00213-025-06993-7","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2399-2410"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810954","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":"C57 and DBA mouse strains express distinct cocaine avoidance phenotypes in an operant runway independent of differences in striatal dynorphin-enkephalin balance.","authors":"Bailey C Remmers, In Bae Choi, Kanako Matsumura, Amelia Nicot, Sydney Cox, Lauren K Dobbs","doi":"10.1007/s00213-025-06992-8","DOIUrl":"10.1007/s00213-025-06992-8","url":null,"abstract":"<p><strong>Rationale: </strong>Human self-report data and rodent models indicate cocaine can induce negative affect, which may impact future cocaine use severity. Despite this, understanding of the neurobiology driving cocaine avoidance is limited. Within the striatum, the opioid peptides enkephalin and dynorphin are associated with cocaine reward and aversion, respectively. Additionally, striatal dynorphin signaling resulting from stress or cocaine withdrawal acts as a negative reinforcer to increase cocaine seeking.</p><p><strong>Objectives: </strong>We validated the use of the cocaine self-administration runway in mice to measure the development of cocaine avoidance and tested whether mice with higher relative striatal dynorphin-to-enkephalin expression are resistant to developing cocaine avoidance.</p><p><strong>Methods: </strong>Cocaine avoidance in the self-administration runway was measured compared to positive (food) and neutral (saline) controls. We tested two inbred mouse strains, C57BL/6J and DBA/2J, known to have opposite striatal dynorphin/enkephalin milieus, and in mice lacking enkephalin selectively from striatal medium spiny neurons (D2-PenkKO).</p><p><strong>Results: </strong>Both inbred strains developed cocaine avoidance, though they expressed it differently. Across training, DBA/2J mice increased their latency to self-administer cocaine, and C57BL/6J increased the number of retreats away from the cocaine-paired goal box. D2-PenkKOs developed similar cocaine avoidance compared to littermate controls.</p><p><strong>Conclusions: </strong>Mice develop avoidance to self-administer cocaine in the runway across a range of strains. Pre-existing strain differences in the striatal dynorphin/enkephalin milieu, however, do not appear to alter the development of cocaine avoidance, and striatal enkephalin is not necessary for the development of cocaine avoidance. This suggests higher relative striatal dynorphin does not facilitate cocaine seeking by mitigating cocaine avoidance.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2379-2398"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132959","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":"Differentiating e-cigarette use and dual use: the role of impulsivity.","authors":"Daniel Hollingworth, Therese Elizabeth Fozard, Katerina Zoe Kolokotroni","doi":"10.1007/s00213-026-07172-y","DOIUrl":"https://doi.org/10.1007/s00213-026-07172-y","url":null,"abstract":"<p><strong>Rationale: </strong>Elevated impulsivity has been associated with vaping, but research has not explored potential differences between e-cigarette-only and dual users of cigarettes and e-cigarettes across multiple dimensions of trait and state impulsivity.</p><p><strong>Objective: </strong>This study examined the differential role impulsivity may play when vaping and smoking occur in isolation, versus when in combination.</p><p><strong>Methods: </strong>Trait impulsivity (UPPS-P) and behavioural impulsivity (monetary delay discounting, cigarette choice, vaping choice, and drug-cue Go/No-go tasks) were compared across non-users (n = 27), cigarette-only (n = 25), e-cigarette-only (n = 26) and dual users (n = 22) recruited online via Prolific.</p><p><strong>Results: </strong>Vaping was associated with heightened sensation seeking, whereas smoking was characterised by elevated negative urgency. Disinhibition was uniquely related to vaping, with dual users demonstrating poorer inhibitory control to nicotine-cues, whilst impulsive choice for non-drug rewards was heightened as a function of smoking and vaping. Importantly, increased preference for immediate gratification within dual users extended to cigarette rewards.</p><p><strong>Conclusions: </strong>Dimensions of impulsivity play distinct roles in vaping and smoking. Whilst heightened impulsive choice may play a critical role in both, preference for novel experiences and diminished inhibitory control may be unique to vaping. Critically, sensitivity to immediate cigarette and monetary rewards, as well as reduced inhibitory control in the presence of nicotine cues, may be associated with an increased risk of initiation and maintenance of dual use. These findings have implications for interventions, policies, and regulations which aim to increase the transition from smoking to vaping, reduce prevalence of dual-use, and support e-cigarette-only users to become nicotine-free.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081919","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":"Moving beyond 5-HT_2A: language models map neurotransmitter receptors to experiential semantics.","authors":"Praneet Suresh, Josie Kins, Lex Levkovskyy, Andrew Thieme, Paul Wren, Tom Ray, Frederick S Barrett, Robin Carhart-Harris, Danilo Bzdok","doi":"10.1007/s00213-026-07170-0","DOIUrl":"https://doi.org/10.1007/s00213-026-07170-0","url":null,"abstract":"<p><strong>Rationale: </strong>Psychedelics exhibit rapid, durable therapeutic effects across diverse psychiatric conditions, yet their broad-spectrum psychoactivity poses challenges for clinical translation.</p><p><strong>Objectives: </strong>As a proof-of-concept, we aimed to quantify associations between 19 neurotransmitter receptors and the subjective effects of 21 psychedelic drugs with broadly assayed binding profiles.</p><p><strong>Methods: </strong>We used a custom Global Vectors for Word Representation (GloVe)-based semantic embedding model trained on 4,496 firsthand experience reports and integrated it with receptor affinities to identify candidate receptor-linked semantic patterns related to distinct psychoactive effects without imposing predefined categorization systems.</p><p><strong>Results: </strong>While 5-HT_2A predictably associates with classic facets of psychedelic experience, our analysis reveals novel associations, including 5-HT_1A and 5-HT_1B with 'Cognitive Disruption', H₁ with 'Interdimensional Communication', and 5-HT_7a and 5-HT_1E with 'Visual Complexity'.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081930","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":"The mechanism underlying tardive dyskinesia: an exploratory test of the dopamine overactivity hypothesis using MRI imaging of midbrain neuromelanin.","authors":"Bernard R Bukala, Luke J Vano, Richard Carr, Alistair Cannon, Connor Cummings, David Davies, Robert McCutcheon, Ben Statton, Alaine Berry, Jan Sedlacik, Daniel Albrecht, Ryan Terry-Lorenzo, Dietrich Haubenberger, Oliver D Howes","doi":"10.1007/s00213-026-07173-x","DOIUrl":"https://doi.org/10.1007/s00213-026-07173-x","url":null,"abstract":"<p><strong>Rationale: </strong>Tardive dyskinesia (TD) is a neurological syndrome of involuntary repetitive movements which results from treatment with antipsychotic medication. The pathoetiology of TD is not well understood but a possible mechanism involves dopaminergic overactivity in the nigrostriatal pathway. If this theory is correct, then levels of neuromelanin (a long-term marker of dopaminergic activity) should be higher in people with TD than those without TD.</p><p><strong>Objectives: </strong>The aim of the study was to test the hypothesis that neuromelanin levels are higher in patients with TD relative to those without TD.</p><p><strong>Methods: </strong>Data from 27 participants (TD: n = 13; non-TD n = 14) with a diagnosis of schizophrenia, all taking antipsychotic drugs, were used. Neuromelanin was measured in the midbrain via Magnetic Resonance Imaging (MRI) and compared between the groups. Movement symptoms were measured using the Abnormal Involuntary Movement Scale (AIMS), and antipsychotic dose recorded.</p><p><strong>Results: </strong>MRI-measured neuromelanin levels were significantly higher in patients with TD, as compared to those without (mean = 0.223; t(17.27) = 3.817, p = 0.001; g = 1.386, 95% CI=[0.559, 2.213]). This remained significant after controlling for age, sex, substantia nigra/ventral tegmental area volume and antipsychotic dose (ANCOVA: F(1,20) = 12.08, p = 0.0024; adjusted β = 0.0301, 95% CI [0.0120, 0.0481]). The most pronounced difference was seen in the ventral substantia nigra.</p><p><strong>Conclusions: </strong>The finding of higher midbrain neuromelanin in patients with TD aligns with the dopamine overactivity hypothesis of TD aetiology. It also supports a neurobiological basis for treatment of TD with drugs that target presynaptic dopamine activity, such as VMAT2 inhibitors. Additionally, it identifies the ventral substantia nigra as a key locus. Future longitudinal studies are needed to delineate if dopamine overactivity develops in response to antipsychotic treatment or is a trait vulnerability marker for risk of TD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081914","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":"The monoterpenes ⍺-pinene and limonene augment or mitigate THC-induced impairments in sustained attention in rats.","authors":"Catherine F Moore, Travis J Wilberger, Bryan W Jenkins, Ryan Vandrey, Elise M Weerts","doi":"10.1007/s00213-026-07158-w","DOIUrl":"https://doi.org/10.1007/s00213-026-07158-w","url":null,"abstract":"<p><strong>Rationale: </strong>α-pinene and limonene are two monoterpenes found in cannabis and cannabis products containing Δ-9-tetrahydrocannabinol (THC). These terpenes are often purported to alter the effects of THC, but empirical data are lacking.</p><p><strong>Objectives: </strong>The current study sought to determine whether orally administered α-pinene and limonene in combination with THC, would mitigate or augment the adverse effects of THC on performance of a cognitive task of sustained attention in rodents.</p><p><strong>Methods: </strong>Male and female Sprague-Dawley rats (n = 24, 50% female) were trained in the rodent psychomotor vigilance task (rPVT). Rats received single or combined doses of THC (3 and 10 mg/kg) and one terpene (10-100 mg/kg; limonene or α-pinene) or vehicle (sesame oil) via oral gavage 60-min prior to rPVT test sessions. Data were analyzed with linear mixed models with sex, THC dose, and terpene dose as factors, accepting p < 0.05 as significant.</p><p><strong>Results: </strong>THC dose-dependently reduced accuracy and increased lapses in the rPVT. When administered alone, α-pinene tended to reduce accuracy and increase lapses at the highest dose (100 mg/kg); limonene alone had no effect on rPVT performance at any doses tested. α-pinene (100 mg/kg) exacerbated performance impairments when administered in combination with a moderate dose of THC (3 mg/kg) but mitigated some effects of a high dose THC (10 mg/kg) on rPVT performance (at α-pinene doses 10-30 mg/kg). Limonene (10-100 mg/kg) mitigated performance impairments from 3 mg/kg THC, but not 10 mg/kg THC.</p><p><strong>Conclusions: </strong>These data lend support to the idea that terpenes found in cannabis can modulate the cognitive effects of the psychoactive constituent THC.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064253","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}