Psychopharmacology最新文献

{"title":"Chronic ethanol exposure reduces resting state functional connectivity and regional synchrony in male rats.","authors":"Elizabeth J Crofton, Sung-Ho Lee, Woomi Ban, Tzu-Wen Winnie Wang, Yen-Yu Ian Shih, A Leslie Morrow, Melissa A Herman","doi":"10.1007/s00213-025-06881-0","DOIUrl":"10.1007/s00213-025-06881-0","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol use disorder (AUD) is a common mental health disorder affecting many individuals and their families in the United States. The effects of alcohol are not fully understood, particularly the effect of alcohol on baseline brain activity.</p><p><strong>Objectives: </strong>We aimed to assess whether chronic ethanol exposure alters resting state functional connectivity between regions of interest (ROIs) previously associated with addiction in male rats. We also aimed to assess whether inhibition of histone deacetylases (HDAC) reduced or blocked the effects of chronic ethanol exposure. Finally, we aimed to investigate whether chronic ethanol exposure altered regional homogeneity (ReHo) and whether HDAC inhibition blocked the effects of ethanol on ReHo.</p><p><strong>Methods: </strong>Male rats were administered water or ethanol (5 g/kg, 25% v/v) via intragastric gavage once daily during the light cycle for 14 days and allowed to withdraw for 24 h. Rats were additionally injected with either the HDAC inhibitor trichostatin A (TSA) (2 mg/kg, i.p.) or vehicle (10% DMSO in 0.9% saline) on the last two days of gavage and on the last day of withdrawal. Rats were scanned with magnetic resonance imaging (MRI) to obtain an anatomical scan as well as resting state functional connectivity (rs-fMRI).</p><p><strong>Results: </strong>We found that chronic ethanol exposure decreased rs-fMRI in the following pairs of ROIs: caudate putamen-prelimbic cortex, caudate putamen-infralimbic cortex, caudate putamen-nucleus accumbens core as well as caudate putamen-insula, insula-prelimbic cortex, and insula-infralimbic cortex. Chronic ethanol exposure also decreased ReHo, particularly in the dorsal striatum. We did not find significant effects of inhibition of HDACs on rs-fMRI of ROIs or ReHo.</p><p><strong>Conclusions: </strong>Chronic alcohol exposure and withdrawal decreases baseline functional connectivity and local synchrony in male rats which is not affected by HDAC inhibition. Future studies should examine the effects of alcohol on resting state connectivity in female rats as well as in voluntary alcohol consumption paradigms. Understanding baseline differences may open new therapeutic avenues in alcohol abuse and AUD to restore typical resting state connectivity.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874829","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":"Glutamate delta-1 receptors regulate a tonic excitatory conductance in the mouse bed nucleus of the stria terminalis and influence neuronal function.","authors":"Sara Y Conley, Sarah E Sizer, Madigan L Bedard, Sara Faccidomo, Clyde W Hodge, Zoé A McElligott","doi":"10.1007/s00213-025-06876-x","DOIUrl":"https://doi.org/10.1007/s00213-025-06876-x","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874830","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 GPR139 agonist TAK-041 produces time-dependent alterations to cerebral blood flow and reward system function in patients with schizophrenia: a randomised placebo-controlled trial.","authors":"Peter C T Hawkins, Adam J Schwarz, James M Stone, Fiona Pepper, James Gilleen, Sam Gijsen, Ndabezinhle Mazibuko, Dimitrios Arkilo, Wei Yin, Jingtao Wu, Polyna Khudyakov, Rhett Behrje, Laura Rosen, Joel Posener, Mitul A Mehta, Antonio Laurenza","doi":"10.1007/s00213-025-06884-x","DOIUrl":"https://doi.org/10.1007/s00213-025-06884-x","url":null,"abstract":"<p><p>The negative and cognitive symptoms of schizophrenia are predictive of quality of life and functional recovery, but there are no approved drug options that target these symptoms directly. TAK-041 (also known as NBI-1065846) is a selective and potent small-molecule agonist of GPR139, an orphan G-protein-coupled receptor, which has been shown to reverse deficits related to negative and cognitive symptoms in animal models. In this proof-of-activity study to evaluate the effects of TAK-041 on motivational anhedonia, 23 adults with schizophrenia experiencing moderate to severe negative symptoms were administered a single 40 mg or 160 mg dose of TAK-041 in a randomised, double-blind, placebo-controlled, two-period crossover design. Functional magnetic resonance imaging (fMRI) assessment of reward function (monetary incentive delay [MID] task) and cerebral blood flow (CBF), as well as cognitive assessment with the Brief Assessment of Cognition in Schizophrenia (BACS) tool, were performed 3 h post dose and after 14 days. There was no significant effect of TAK-041 compared with placebo on BACS score at either timepoint. There was also no significant effect of TAK-041 on MID fMRI at day 1; however, at day 14, TAK-041 produced an increase in reward anticipatory activity in the ventral striatum compared with placebo. There was a significant decrease in CBF throughout the brain at day 1 that then reversed, resulting in a relative increase at day 14, compared with placebo. At day 14 there was a significant interaction between drug and CBF on reward anticipatory BOLD, indicating that drug-related changes to CBF may partially contribute to the observed BOLD effects (although the main effect of drug on the BOLD signal remained significant after including CBF as a covariate in the model). These data indicate that TAK-041 produces detectable changes in both CBF and reward task related fMRI signal in brain regions linked with symptoms and treatment response in schizophrenia. IND Number: 130074| EudraCT Number: 2017-001084-20| Clincaltrails.gov registry: NCT03319953.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859558","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":"Response to Barner et al. (2025) on comment on Zabik et al. (2024): special considerations for cannabis research in RCTs and feasibility in a clinical setting.","authors":"Joshua Aviram","doi":"10.1007/s00213-025-06883-y","DOIUrl":"https://doi.org/10.1007/s00213-025-06883-y","url":null,"abstract":"","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856197","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":"Ascending single-dose study of the safety, pharmacokinetics, and pharmacodynamics of CSTI-500, a novel monoamine triple reuptake inhibitor, first-in-human.","authors":"Lieuwe Appel, Robert Risinger, Anders Wall, Harald Murck, Shuang Liu, Gunnar Antoni, Roger Lane","doi":"10.1007/s00213-025-06861-4","DOIUrl":"https://doi.org/10.1007/s00213-025-06861-4","url":null,"abstract":"<p><strong>Rationale: </strong>Monoamine triple reuptake inhibitors (TRIs) inhibit central dopamine, norepinephrine, and serotonin transporters, restoring functional monoamine neurotransmission.</p><p><strong>Objectives: </strong>This clinical trial evaluated the safety, tolerability, and pharmacokinetics in healthy volunteers after single-ascending-doses (SAD) of the novel monoamine TRI CSTI-500. In addition, we estimated the peak and duration of striatal serotonin transporter (SERT) and dopamine transporter (DAT) occupancies, by using positron emission tomography (PET).</p><p><strong>Methods: </strong>Part A was a double-blinded, randomized, placebo-controlled, sequential SAD study with seven sequential dose panels (0.5-150 mg) where subjects in each panel received either a single oral dose of CSTI-500 (n=6) or placebo (n=2). Part B was an open-label, single-dose PET study to assess the peak and duration of SERT (n=4) and DAT (n=5) striatal occupancies, using the radioligands [¹¹C]MADAM and [¹¹C]PE2I, respectively.</p><p><strong>Results: </strong>The maximum tolerable acute single-dose of CSTI-500 was determined as 100 mg. No serious adverse events occurred. The median maximum CSTI-500 concentrations were attained at 1-2 hours post-dose (h pd); the estimated plasma elimination half-life was 44-50 h pd. Subsequent to a single-dose of 100 mg CSTI-500, mean striatal SERT occupancy was 72% and 62% at 4-6 and 24 h pd, respectively. Mean striatal DAT occupancy was 36% and 31% at 4-9 and 24 h pd, respectively.</p><p><strong>Conclusions: </strong>CSTI-500 is a potent monoamine TRI with substantial striatal SERT and moderate DAT occupancies in healthy subjects. Together with promising safety-tolerability and pharmacokinetics profiles, the continued clinical development of CSTI-500 is strongly supported.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817379","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":"Psychedelic researchers' own experiences of psychedelic substances, their link to opinions of psychedelics, and reflections on positionality.","authors":"Jussi Jylkkä, Aila Mustamo","doi":"10.1007/s00213-025-06871-2","DOIUrl":"https://doi.org/10.1007/s00213-025-06871-2","url":null,"abstract":"<p><strong>Rationale: </strong>Anecdotal evidence suggests that psychedelic researchers often have personal experiences with psychedelic substances. While such experiences may benefit research, concerns have been raised about potential biases and \"excessive enthusiasm.\" However, the prevalence of personal experiences, their perceived relevance, and their association with opinions about psychedelics remain underexplored.</p><p><strong>Objectives: </strong>This study aimed to investigate how common personal psychedelic experiences are among psychedelic researchers, their perceived relevance to research, and whether personal use is associated with opinions about psychedelics.</p><p><strong>Methods: </strong>Participants (N = 111) conducting psychedelic research in academic settings were recruited. Data were collected on personal experiences, their perceived relevance, and opinions about psychedelics. Regression analyses examined associations between personal use and opinions.</p><p><strong>Results: </strong>Most respondents (85%) reported personal experiences with classic psychedelics. On average, they saw personal experience as beneficial for research, but also as potential source of bias. They acknowledged the importance of self-reflection and the need to disclose personal experiences, but found disclosure challenging in practice. Personal use predicted more positive opinions about psychedelics' potential to improve well-being, transform society, address the ecological crisis, and answer spiritual questions (regression βs = 0.3 - 0.5, ps < 0.01).</p><p><strong>Conclusions: </strong>The findings highlight the prevalence of personal psychedelic experiences among this sample of researchers and their influence on research interests and opinions. The results underscore the need for open discussion and reflection. Future studies should explore whether the observed associations reflect causal relationships or potential biases.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817380","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":"Application of nanomaterials in central nervous system disorders.","authors":"Yixuan Deng, Yani Feng, Bangming Ye, Lei Hu, Lixin Qi, Chenyi Wang, Chunting Zhou, Guanhao Liu, Xiuying Gao, Congying Lin, Qiang Ding, Ziming Zhao, Chunyu Song, Bo Qian, Tianhao Wu, Xingyun Wang, Zhiming Liu, Zhenlang Lin, Min Zhang","doi":"10.1007/s00213-025-06862-3","DOIUrl":"https://doi.org/10.1007/s00213-025-06862-3","url":null,"abstract":"<p><p>There is a common mechanism in the pathogenesis of central nervous system diseases: Neuronal damage causes a dissipation of the intermediate metabolites, triggering a wider range of injury and inflammation. Due to the selective permeability of the blood-brain barrier, the drug treatment of neurological diseases is not effective. Nanomedicine, with good biocompatibility and high plasticity, can pass through the blood-brain barrier through various mechanisms and targeted the lesion: The nano-delivery system helps drugs cross the blood-brain barrier while taking advantage of its high drug-loading capacity to achieve combined treatment; Nano-enzymes can simulate the enzymatic reaction in biological body to remove metabolic substances, and are more stable and economical than biological enzymes; Individual nanomedicine can regulate the differentiation process of neural stem cells from the genetic level, increase the number of neurons, and repair injured nerves. Nanomaterials can not only improve the pharmacokinetics and pharmacodynamics, but also play the function of focal location to monitor and evaluate the disease and condition during the treatment of nervous system diseases. In this paper, the mechanism of nanomaterials penetrating the blood-brain barrier (BBB) and locating lesions in various nervous system diseases is reviewed, which opens up new ideas for further exploring the application of nanotechnology in central nervous system diseases.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800051","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":"Montelukast attenuated memory decline, neuroinflammatory and neurodegenerative biomarkers in Aβ_1-42 exposed model of alzheimer's disease in mice.","authors":"Sneha Balki, Avtar Singh Gautam, Paul Gajanan Balaji, Awesh Kumar Yadav, Rakesh Kumar Singh","doi":"10.1007/s00213-025-06865-0","DOIUrl":"https://doi.org/10.1007/s00213-025-06865-0","url":null,"abstract":"<p><p>Alzheimer's disease (AD) represents major cognitive and memory decline in the elderly patients. Although Montelukast has traditionally been used for the treatment of asthma, its role in prevention of neuropathological changes and memory decline in AD have recently been reported in literature. However, the brain availability through oral administration of Montelukast is limited due to its poor blood-brain barrier permeation. This study has highlighted that the intranasal administration of Montelukast can provide a considerable brain bioavailability of Montelukast in mice. In addition, intranasal administration of Montelukast showed a significant improvement of spatial and cognitive memory, prevention of Aβ accumulation, astrocyte activation, along with improved redox balance and neuronal density in the hippocampus and cortex regions in the amyloid-beta_1-42 (Aβ_1-42)-induced animal model of AD. These neuroprotective effects were found to be better through intranasal administration of Montelukast in comparison to its oral administration at the equivalent dose. These results suggest that Montelukast may be administered through intranasal route to achieve a significant therapeutic effect in the pathophysiology of AD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795201","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":"Methylphenidate (Ritalin) does not improve exam performance in an experimental setting.","authors":"Anke Sambeth, Monika Toth, Arjan Blokland","doi":"10.1007/s00213-025-06864-1","DOIUrl":"https://doi.org/10.1007/s00213-025-06864-1","url":null,"abstract":"<p><strong>Rationale: </strong>Surveys indicate that about 10-20% of students use medicinal drugs to improve their exam performance. Whether these drugs really improve exam performance has not been examined in an experimental setting yet. This study tested the effects of methylphenidate (MPH; 20 mg) on exam performance either by giving the drug before studying for an exam (day 1, acquiring new information) or before the exam was taken (day 2, retrieving the information).</p><p><strong>Method: </strong>For this study, a double-blind placebo controlled between-subjects design was applied. The participants were randomly assigned to three groups that were given treatment on the two days: Placebo-Placebo (n = 25), MPH (n = 24), Placebo-MPH (n = 26). The exam contained multiple-choice questions (factual knowledge and inference questions) and open questions (inference).</p><p><strong>Results: </strong>The data showed that MPH did not improve the exam performance on the three types of questions. In addition, the average grade did not differ between the three groups and the number of participants failing or passing the exam did not differ.</p><p><strong>Conclusion: </strong>This is a first experimental study showing that MPH does not improve exam performance and should discourage students to take MPH during exam periods.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785143","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":"Triggered temptations: A new procedure to compare reward-seeking behaviour induced by discriminative and conditioned stimuli in rats.","authors":"Mandy Rita LeCocq, Shaghayegh Najafipashaki, Domiziana Casale, Isabel Laplante, Anne-Noël Samaha","doi":"10.1007/s00213-025-06764-4","DOIUrl":"10.1007/s00213-025-06764-4","url":null,"abstract":"<p><strong>Rationale: </strong>Environmental cues guide animals towards resources vital for survival but can also drive maladaptive reward-seeking behaviours, as in gambling and eating disorders. While conditioned stimuli (CSs) are paired with reward delivery after reward-seeking actions, discriminative stimuli (DSs) signal reward availability independently of behaviour.</p><p><strong>Objective: </strong>We introduce a procedure to compare CS and DS effects on reward-seeking behaviour, in the same subjects within a single session.</p><p><strong>Methods: </strong>Female and male Sprague-Dawley rats learned to self-administer sucrose. During each session, DS+ trials signaled that lever pressing would produce sucrose paired with a CS+ , and DS- trials signaled no sucrose and a CS-. Next, in the absence of sucrose, we assessed the ability of the cues to i) reinforce lever pressing and ii) increase sucrose seeking when presented response-independently. We also assessed the effects of the mGlu_2/3 receptor agonist LY379268 and d-amphetamine on cue-induced sucrose seeking.</p><p><strong>Results: </strong>By the end of self-administration training, lever pressing peaked during DS+ trials and dropped during DS- trials. The DS+ was a conditioned reinforcer of sucrose seeking in both sexes, whereas the CS+ was more effective in males. Response-independent presentations of the DS+ invigorated sucrose seeking in both sexes, whereas the CS+ was effective only in males. LY379268 suppressed DS+ -triggered sucrose seeking in females, with no effect in males. D-amphetamine enhanced sucrose seeking non-specifically across cue conditions in males, with no effect in females.</p><p><strong>Conclusions: </strong>Our new trial-based procedure can be used to identify unique and similar mechanisms underlying DS and CS influences on appetitive behaviour.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1811-1832"},"PeriodicalIF":3.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493151","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}