Psychopharmacology最新文献

{"title":"Verbascoside reverses GABAergic deficits in the prefrontal cortex to alleviate chronic Stress-Induced depression.","authors":"Jin Pan, Liuxuan Huang, Peng Sun, Haoquan Tian, Wenguang Yang, Xinyu Fang, Feng Li, Ke Ma","doi":"10.1007/s00213-025-06894-9","DOIUrl":"https://doi.org/10.1007/s00213-025-06894-9","url":null,"abstract":"<p><strong>Background: </strong>The dysregulation of prefrontal synaptic transmission accompanied by γ-aminobutyric acid (GABA) deficit, is crucial in depression. Previously, we have demonstrated that Baihe Dihuang decoction with verbascoside (VB) as one of the main active ingredients attenuates prefrontal interneurons deficits through synthesis and release of GABA negatively regulated by miR-144-3p, but the potential mechanism through which VB reverses the dysfunction of stress-induced aberrant prefrontal GABAergic neurons through miRNAs/Gad-67/VGAT signaling remains elusive.</p><p><strong>Methods: </strong>The antidepressant effects and neuroprotective function of VB were observed by a chronic stress-induced depression and corticosterone (CORT)-stimulated nerve cell injury model, respectively. Specific changes in prefrontal GABAergic miR-144-3p expression were used to assess the action of VB acting on GABA release.</p><p><strong>Results: </strong>High-expression prefrontal miR-144-3p was associated with depression-like behaviors caused by long time stress, reflected by altered GABA tone. Supplementation with VB attenuated chronic stress-induced prefrontal cortex neuron injury and prefrontal GABAergic deficit by downregulating miR-144-3p expression, as well as obviously improved the relative abundance of beneficial GABA-producing bacteria. However, antidepressant-like effects by VB were antagonized by overexpressed miR-144-3p in frontal cortex GABAergic neurons. Similarly, VB administration caused reduced expression of miR-144-3p against impaired GABA production. In the CORT-induced nerve cell injury model, The pharmacological effect of VB promoting GABA release ability and exerting neuroprotection is strongly reversed by overexpression of miR-144-3p.</p><p><strong>Conclusion: </strong>This study elucidated that miR-144-3p down-regulated GABAergic neurons activation in the medial prefrontal cortex was sufficient and necessary for VB antidepressant responses.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040886","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":"Effects of psychostimulants on locomotor activity in the BTBR T⁺ Itpr3^tf/J mouse: implications for comorbid autism spectrum disorder and attention deficit hyperactivity disorder.","authors":"William E Fantegrossi, Hannah E Shaw, Stephen A Fagot, Kamryn Thomas, Harpreet Kaur","doi":"10.1007/s00213-025-06908-6","DOIUrl":"https://doi.org/10.1007/s00213-025-06908-6","url":null,"abstract":"<p><strong>Rationale: </strong>People with autism spectrum disorder (ASD) often have psychiatric comorbidities, with attention deficit hyperactivity disorder (ADHD) being the most common. Psychostimulants used as ADHD treatments are less effective in these dual diagnosis individuals, with lower rates of symptom improvement and a higher incidence of adverse drug effects. The mutant BTBR T⁺ Itpr3^tf/J mouse (BTBR) may serve as a model for comorbid ADHD and ASD, however, few studies have assessed the effects of psychostimulants in these animals.</p><p><strong>Objectives: </strong>We determined dose-effect curves for locomotor effects of 10 different psychostimulants in adult male BTBR and C57Bl/6 N (C57) mice, including amphetamine and other monoamine releasers, methylphenidate and other reuptake inhibitors, as well as some drugs with a mixed profile of monoamine release and reuptake inhibition.</p><p><strong>Methods: </strong>Mice were surgically implanted with radiotelemetry probes which measured locomotor activity within the home cage.</p><p><strong>Results: </strong>A robust strain difference was typically observed at large doses, wherein C57 mice entered motor stereotypy while BTBRs did not. This resistance to stereotypy in BTBR mice resulted in dramatically increased locomotor stimulant effects across drugs.</p><p><strong>Conclusions: </strong>Because resistance to locomotor stereotypy in BTBRs was observed among psychostimulants with distinct mechanisms of action and selectivities for monoamine transporters, it is likely that pervasive neurobiological and/or metabolic differences in BTBR mice mediate this effect. Further studies to determine the mechanisms underlying the exaggerated locomotor responses to psychostimulants in BTBR mice are needed. Results of these studies may guide drug development efforts toward identifying more effective and better-tolerated medications for comorbid ASD with ADHD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034243","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":"Identification and prioritization of gene sets associated with schizophrenia risk by network analysis.","authors":"Minglan Yu, Qingyu Tan, Wei Dong, Bo Xiang","doi":"10.1007/s00213-025-06867-y","DOIUrl":"https://doi.org/10.1007/s00213-025-06867-y","url":null,"abstract":"<p><strong>Rationale: </strong>Genome-wide association studies (GWASs) are used to identify genetic variants for association with schizophrenia (SCZ) risk; however, each GWAS can only reveal a small fraction of this association.</p><p><strong>Objectives: </strong>This study systematically analyzed multiple GWAS data sets to identify gene subnetwork and pathways associated with SCZ.</p><p><strong>Methods: </strong>We identified gene subnetwork using dmGWAS program by combining SCZ GWASs and a human interaction network, performed gene-set analysis to test the association of gene subnetwork with clinical symptom scores and disease state, meanwhile, conducted spatiotemporal and tissue-specific expression patterns and cell-type-specific analysis of genes in the subnetwork.</p><p><strong>Results: </strong>We identified a gene subnetwork comprising 48 genes was associated with SCZ, and confirmed gene subnetwork's gene-set association with SCZ (Case vs. Control) in two independent cohorts. Gene prioritization identified CALM1 and TCF4 as hub genes in the subnetwork. Meanwhile, using gene-set analysis, it was determined that the gene subnetwork was also linked to generality symptoms and Positive and Negative Syndrome Scale (PANSS) total score in SCZ. 12 out of 48 genes were higher expression in early prenatal brain. In addition, expressions of CALM1, NCAM1, and TCF4 were dysregulated in cerebral organoids of SCZ patients compared with healthy controls. CALM1 and NCAM1 were mainly expressed on the surface of glutamatergic neurons.</p><p><strong>Conclusions: </strong>Our findings identified CALM1, NCAM1, and TCF4 as SCZ risk genes and provided important clues to support the neurodevelopmental hypothesis and new therapeutic targets of SCZ.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030459","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":"Alteration in hippocampal mitochondria ultrastructure and cholesterol accumulation linked to mitochondrial dysfunction in the valproic acid rat model of autism spectrum disorders.","authors":"Paula D Prince, Martín G Codagnone, Javier A W Opezzo, Juan S Adán Areán, Christian Höcht, Nathalie Arnal, Silvia Alvarez, Sandra Zárate, Analía Reinés","doi":"10.1007/s00213-025-06899-4","DOIUrl":"https://doi.org/10.1007/s00213-025-06899-4","url":null,"abstract":"<p><strong>Rationale: </strong>Autism spectrum disorders (ASD) are a group of neurodevelopmental and multifactorial conditions with cognitive manifestations. The valproic acid (VPA) rat model is a well-validated model that successfully reproduces the behavioral and neuroanatomical alterations of ASD. Previous studies found atypical brain connectivity and metabolic patterns in VPA animals: local glucose hypermetabolism in the prefrontal cortex, with no metabolic changes in the hippocampus.</p><p><strong>Aim: </strong>This study aimed to explore mitochondrial structural features, lipid content, and functionality in the hippocampus and cerebral cortex in the VPA model.</p><p><strong>Methods: </strong>On embryonic day 10.5, pregnant Wistar rats were injected with VPA (450 mg/kg) or saline solution. In the hippocampus and cerebral cortex of male offspring (postnatal day 35), the mitochondrial structure was evaluated by transmission electron microscopy, oxidized/reduced glutathione was determined by high-performance liquid chromatography, mitochondrial membrane cholesterol, and phospholipids were determined by thin-layer chromatography, and oxygen consumption and ATP synthesis were measured in isolated mitochondria.</p><p><strong>Results: </strong>Mitochondrial increased oxygen consumption and decreased ATP production, increased oxidized/reduced glutathione, cholesterol accumulation in mitochondrial membrane and altered mitochondrial structure were found in the hippocampus of VPA animals. All parameters were preserved in the cerebral cortex of VPA rats.</p><p><strong>Conclusions: </strong>These findings reveal brain region-specific mitochondrial structural and functional alterations in VPA-treated animals, with preserved mitochondria in regions with high glucose demand and impaired mitochondria in metabolically normal areas. Moreover, cholesterol accumulation in hippocampal mitochondrial membranes is a potential cause of mitochondrial dysfunction, contributing to a prooxidant state.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030410","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":"Photostimulation of locus coeruleus CA1 catecholaminergic terminals reversed Spatial memory impairment in an alzheimer's disease mouse model.","authors":"Donovan K Gálvez-Márquez, Oscar Urrego-Morales, Luis F Rodríguez-Durán, Federico Bermudez-Rattoni","doi":"10.1007/s00213-025-06885-w","DOIUrl":"https://doi.org/10.1007/s00213-025-06885-w","url":null,"abstract":"<p><strong>Rationale: </strong>One of the earliest changes associated with Alzheimer's disease (AD) is the loss of catecholaminergic terminals in the cortex and hippocampus originating from the Locus Coeruleus (LC). This decline leads to reduced catecholaminergic neurotransmitters in the hippocampus, affecting synaptic plasticity and spatial memory. However, it is unclear whether restoring catecholaminergic transmission in the terminals from the LC may alleviate the spatial memory deficits associated with AD.</p><p><strong>Objectives: </strong>This study aims to investigate the effects of optogenetic stimulation of LC catecholaminergic projections on alleviating spatial memory and synaptic plasticity deficits associated with AD.</p><p><strong>Methods: </strong>We conducted experiments using a 12-month-old 3xTgAD mouse model (AD-TH) that expresses Cre recombinase under the control of the tyrosine hydroxylase (TH) gene. This model enabled us to photostimulate the terminals from the LC in the hippocampal CA1 region before performing two different spatial memory tasks and inducing long-term plasticity.</p><p><strong>Results: </strong>Optogenetic stimulation successfully reversed the impairment of spatial memory retrieval in aging AD-TH mice. Furthermore, this stimulation restored levels of catecholaminergic neurotransmitters in the hippocampus and enhanced synaptic plasticity, as demonstrated by a long-term potentiation (LTP) protocol.</p><p><strong>Conclusions: </strong>These findings suggest a critical role for the LC-hippocampal CA1 catecholaminergic circuitry in disrupting synaptic plasticity and the spatial memory deficits characteristic of the early stages of AD. The study highlights the potential for targeting LC catecholaminergic pathways as a therapeutic strategy to improve cognitive deficits experienced by AD patients.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024198","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":"Short-term residual effects of smoked cannabis on simulated driving performance.","authors":"Kyle F Mastropietro, Jake A Rattigan, Anya Umlauf, David J Grelotti, Marilyn A Huestis, Raymond T Suhandynata, Igor Grant, Robert L Fitzgerald, Thomas D Marcotte","doi":"10.1007/s00213-025-06880-1","DOIUrl":"10.1007/s00213-025-06880-1","url":null,"abstract":"<p><strong>Rationale: </strong>Between periods of use, chronic cannabis consumers may display residual effects on selective cognitive functions, particularly memory and attention. Whether there are comparable deficits in real-world behaviors, such as driving, has not been thoroughly examined.</p><p><strong>Objectives: </strong>The current study explored the association between driving simulator performance, cannabis use history, and demographic factors after ≥ 48 h of abstinence. Study I examined simulator performance across a broad range of use within 191 healthy cannabis users. Study II compared performance between participants with the highest cannabis use intensity and a non-cannabis-using comparison group.</p><p><strong>Methods: </strong>In Study I, 191 healthy cannabis users completed a 25-minute simulated drive, following ≥ 48 h of abstinence. In Study II, a pilot study comprising a subset of 18 frequent cannabis users was compared to 12 non-using controls who completed identical driving measures in a separate study. In both studies, the main outcome was the Composite Drive Score (CDS), a global measure of driving performance comprising key driving-related variables, including standard deviation of lateral position.</p><p><strong>Results: </strong>In Study I, there was no relationship between CDS, its subtests, measures of cannabis use history, or demographic variables (all ps > 0.10). In Study II, frequent cannabis users and the non-using comparison group did not differ on CDS or performance on its subtests (all ps > 0.40).</p><p><strong>Conclusions: </strong>The current study did not find evidence of a residual effect of cannabis on simulated driving performance during a short period of cannabis abstinence. Future studies would benefit from inclusion of larger non-cannabis-using comparison groups.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006587","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":"Too big to fail? Comparing effect sizes of MDMA assisted therapy to unmasking bias.","authors":"Balázs Szigeti, Ellen R Bradley, Joshua Woolley","doi":"10.1007/s00213-025-06886-9","DOIUrl":"https://doi.org/10.1007/s00213-025-06886-9","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993182","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 quercetin-serotonin transporter (SERT) connection: a new hope for depression therapy?","authors":"Meesala Krishna Murthy","doi":"10.1007/s00213-025-06889-6","DOIUrl":"https://doi.org/10.1007/s00213-025-06889-6","url":null,"abstract":"<p><p>Quercetin, a naturally occurring flavonoid, has been found to be a potential agent for the treatment of major depressive disorder (MDD), given the complexity of its interaction with the serotonin transporter (SERT). Clinically, quercetin has direct and indirect modulatory effects as opposed to conventional selective serotonin reuptake inhibitors (SSRI), which act mainly by inhibiting SERT after a time delay and communicate with SERT through possible binding location preferences and allosteric processing, while simultaneously controlling its definite expression through anti-inflammatory and antioxidant pathways, such as the NF-kB, AMPK/SIRT-1, and Nrf2-ARE cascades. These processes assist in modifying serotonergic neurotransmission and minimizing oxidative and inflammatory strains, which are the major contributors to the pathophysiology of depression. Quercetin positively affects neuroplasticity and regulates the gut-to-brain axis, which affirms its antidepressant effects. Preclinical evidence indicates that quercetin can cause more rapid and extensive effects than SSRIs. However, translation issues include poor bioavailability and interindividual variation. Future trials should focus on inflammatory markers and individual quercetin formulations to maximize therapeutic effects in the depressed state.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993214","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 role of melatonin timing on short-term memory retention during sleep restriction.","authors":"Karyme M Alemán-Villa, Hugo J Sosa-Arámbula, David A Armienta-Rojas, Josué Camberos-Barraza, Ángel R Rábago-Monzón, Alejandro Camacho-Zamora, Juan F Osuna-Ramos, Javier A Magaña-Gómez, Alma M Guadrón-Llanos, Loranda Calderón-Zamora, Claudia D Norzagaray-Valenzuela, Marco A Valdez-Flores, Verónica J Picos-Cárdenas, Emiliano Terán-Bobadilla, Alberto K De la Herrán-Arita","doi":"10.1007/s00213-025-06887-8","DOIUrl":"10.1007/s00213-025-06887-8","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966347","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":"Sex specific effects of ketamine, but not other glutamate receptor modulators, on ethanol self-administration and reinstatement of ethanol seeking in rats.","authors":"Megan L Bertholomey, Camryn Forbes, Bryan D McElroy, Mary M Torregrossa","doi":"10.1007/s00213-025-06782-2","DOIUrl":"10.1007/s00213-025-06782-2","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol use and major depressive disorder are frequently comorbid, with individuals diagnosed with a substance use disorder being nearly three times as likely to have major depression. Poor treatment responses are found for both disorders and are further complicated when they co-occur, underscoring the need for better therapies. One potential candidate is ketamine, which has been shown to have rapid and long-lasting effects in individuals with treatment-resistant depression and, in some studies, reduces drinking in alcohol use disorder. However, though women are more likely to have this comorbidity, few studies have examined sex-specific effects of ketamine on alcohol drinking, nor have studies assessed the potential for ketamine to reduce reinstatement of alcohol seeking.</p><p><strong>Objectives: </strong>The primary goal of the present studies was to determine the effects of ketamine on alcohol-motivated behaviors in male and female rats, including in a model of stress + cue-induced reinstatement of alcohol seeking using yohimbine (YOH).</p><p><strong>Results: </strong>We found a selective reduction in alcohol self-administration and YOH + cue-induced reinstatement in females, but not males at a dose of 10 mg/kg ketamine. However, the same dose of ketamine was effective in reducing YOH + cue-induced reinstatement of saccharin seeking in both sexes. In addition, a different NMDAR antagonist, memantine, was effective in reducing alcohol seeking in both sexes, while the ketamine metabolite hydroxynorketamine (HNK) had no effects.</p><p><strong>Conclusions: </strong>In summary, these data suggest that antagonism of NMDARs may be effective in reducing stress-related alcohol seeking, but that ketamine has unique properties that lead to female-specific effects on alcohol seeking.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2035-2045"},"PeriodicalIF":3.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812135","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}