Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Lower perturbational complexity index after transcranial magnetic stimulation in schizophrenia patients","authors":"Vicente Molina ,&nbsp;Inés Fernández-Linsenbarth ,&nbsp;Rosa Beño-Ruiz- de- la- Sierra ,&nbsp;Emma Osorio-Iriarte ,&nbsp;Alejandro Roig ,&nbsp;Antonio Arjona ,&nbsp;Víctor Rodríguez ,&nbsp;Pablo Núñez ,&nbsp;Jesús Poza ,&nbsp;Alvaro Díez-Revuelta ,&nbsp;Claudia Rodríguez-Valbuena ,&nbsp;Gema Mijancos-Martínez ,&nbsp;Alejandro Bachiller ,&nbsp;Miguel Angel Mañanas","doi":"10.1016/j.pnpbp.2025.111254","DOIUrl":"10.1016/j.pnpbp.2025.111254","url":null,"abstract":"<div><h3>Background</h3><div>Informational integration and differentiation of the cortex can be tested by methods such as the perturbational complexity index (PCI) combined with TMS-induced activity perturbation. The PCI is obtained by stimulating the cortex with TMS and measuring the resulting spatiotemporal cortical responses with high-density EEG.</div></div><div><h3>Methods</h3><div>We have compared PCI between 26 patients with schizophrenia (15 males), 15 of them First Episode (FE) (7 males), and 22 healthy controls (12 males).</div></div><div><h3>Results</h3><div>Values of PCI were significantly lower in patients with schizophrenia, as well as in FE considered alone. There was no significant relation between anomalous self-experiences or symptoms and PCI values in the patients: PCI values were unrelated to treatment doses or illness duration.</div></div><div><h3>Conclusions</h3><div>Our data suggest that spatiotemporal cortical responses to TMS pulses are reduced in patients regarding variability or spatial extension, which could imply a lower capacity for sustaining informational complexity.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111254"},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S1PR3 in hippocampal neurons improves synaptic plasticity and decreases depressive behavior via downregulation of RhoA/ROCK1","authors":"Huiqin Liu ,&nbsp;Shuhua Chen ,&nbsp;Hong Xiang ,&nbsp;Jie Xiao ,&nbsp;Shaoli Zhao ,&nbsp;Xiao Zhang ,&nbsp;Zhihao Shu ,&nbsp;Jing Zhang ,&nbsp;Jie Ouyang ,&nbsp;Quanjun Liu ,&nbsp;Qisheng Quan ,&nbsp;Jianing Fan ,&nbsp;Peng Gao ,&nbsp;Xinru Zheng ,&nbsp;Alex F. Chen ,&nbsp;Hongwei Lu","doi":"10.1016/j.pnpbp.2025.111256","DOIUrl":"10.1016/j.pnpbp.2025.111256","url":null,"abstract":"<div><div>The study investigates how Sphingosine-1-phosphate receptor 3 (S1PR3) and the Chronic Unpredictable Mild Stress (CUMS) affects depression-like behaviors. The S1P/S1PR3 signaling pathway is known to play a role in mood regulation, but it is not yet fully understood how it is connected to depression. This study looks to further explore this topic. To investigate the effect of CUMS on S1PR3 expression in hippocampus neurons and the synaptic plasticity, we observed animals' behavior with Sucrose Preference Test (SPT), Forced Swim Test (FST) and Open Field Test (OFT). Combining molecular and histological analysis, we investigated the S1PR3 expression, the change in synapse density, and synaptic structure change in the hippocampus. The CUMS caused a significant decrease in the S1PR3 expression, the density of the synaptic spine and synaptic ultrastructure change in mice. On the other hand, over-expression of S1PR3 by adeno-associated virus (AAV) in hippocampal neurons alleviated the depressive-like behaviors and synaptic deficits observed in stress-susceptible animals. Furthermore, the depressive-like phenotype and synaptic impairments were normalized by the expression of RhoA, implicating the RhoA/ROCK1 pathway in S1PR3 actions. Collectively, our findings provide strong evidence that S1PR3 plays a key role in hippocampal synaptic plasticity and depression and that modulation of S1PR3/RhoA/ROCK1 signaling may offer a novel therapeutic strategy for MDD. This study not only underscores the therapeutic potential of S1PR3 but also provides novel insights into the molecular mechanisms underlying depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111256"},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effectiveness of hyperbaric oxygen therapy in children and adolescents and with autism spectrum disorders: A systematic review and meta-analysis","authors":"Ping Tu ,&nbsp;Xirongguli Halili ,&nbsp;Siyi Zhang ,&nbsp;Jing Yang ,&nbsp;Yongbei Xiao","doi":"10.1016/j.pnpbp.2025.111257","DOIUrl":"10.1016/j.pnpbp.2025.111257","url":null,"abstract":"<div><h3>Background</h3><div>Hyperbaric oxygen therapy (HBOT) is considered a potential treatment for autism spectrum disorders, aiming to improve the underlying pathophysiological mechanisms. It has been studied in several clinical trials, but the effectiveness is still controversial.</div></div><div><h3>Purpose</h3><div>This systematic review aimed to systematically evaluate the effectiveness of hyperbaric oxygen therapy in the treatment of autism in children and adolescents.</div></div><div><h3>Methods</h3><div>We systematically searched seven databases (PubMed, Embase, Cochrane Libraries, Web of Science, CNKI, Wanfang, and SinoMed) up to March 20, 2024, as well as references lists. The included studies evaluated the effect of HBOT on improving the core symptoms of autism and other specific symptoms (e.g., communication, sociability, cognitive awareness, behavior), including RCTs and quasiexperimental studies. The Cochrane Collaboration's Risk of Bias Assessment Tool for Randomized Trials (RoB2.0) and the JBI Risk of Bias Tool for Quasi-Experimental Studies were used as quality assessment tools. A random effects model was used to conduct a meta-analysis of the core and specific symptoms of autism. Sensitivity analyses and meta-regression were performed to identify sources of heterogeneity and assess result robustness. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence certainty analysis was performed for outcomes. This systematic review is registered with PROSPERO (CRD42024527220).</div></div><div><h3>Results</h3><div>A total of 17 studies with 890 patients were ultimately included in the metaanalysis. The meta-analysis revealed moderately large, significant effects of hyperbaric oxygen therapy, reducing core symptoms of autism [SMD = −0.66, 95 % CI (−1.04, −0.28), <em>P</em> = 0.0006], and improving three aspects of daily performances (communication [SMD = −0.88, 95 % CI (−1.71,-0.04), <em>P</em> = 0.04], cognitive awareness [SMD = −0.93, 95 % CI (−1.51, −0.35), <em>P</em> = 0.002], and behavior [SMD = −0.80, 95 % CI (− 1.46, −0.13), <em>P</em> = 0.02] in children and adolescents with autism. This systematic review and meta-analysis have limitations such as poor quality and high heterogeneity of the included study.</div></div><div><h3>Conclusion</h3><div>These findings underscore the potential benefits of hyperbaric oxygen therapy in managing autism-related symptoms and improving daily functioning in affected children and adolescents. Future rigorously designed, high-quality studies are required to confirm the efficacy of hyperbaric oxygen therapy and establish standard treatment protocols.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111257"},"PeriodicalIF":5.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurobiological mechanisms of antidepressant properties of psilocybin: A systematic review of blood biomarkers.","authors":"Juliana Lima Constantino, Jens H van Dalfsen, Sara Massetti, Jeanine Kamphuis, Robert A Schoevers","doi":"10.1016/j.pnpbp.2025.111251","DOIUrl":"10.1016/j.pnpbp.2025.111251","url":null,"abstract":"<p><p>Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize the results of human studies investigating changes in blood-based biomarkers of MDD to guide future research on potentially relevant analytes that could be monitored in clinical trials. A systematic search was performed in MEDLINE, Embase, and Web of Science to retrieve studies investigating changes in serum and plasma levels of neurotrophic, immunologic, neuroendocrine, and metabolic markers. Nine studies were included, describing findings on 15 biomarkers, exclusively in healthy participants. Studies consistently reported a decrease in interleukin-6, C-reactive protein, and eosinophils, and an increase in cortisol, prolactin, oxytocin, thyroid-stimulating hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, and free fatty acids following psilocybin administration. Less consistent effects were observed on interleukin-1β, interleukin-8, tumour necrosis factor-alpha, soluble urokinase plasminogen activator receptor, and growth hormone. The results are in line with preclinical studies and provide initial support from human studies that psilocybin potentially leads to beneficial effects on biomarkers of MDD. However, given the limited number of studies, findings should be approached with caution prior to replication. Further research should include larger samples, clinical populations, longer-term assessment, rigorous experimental designs, and account for the potential confounding of psychological stress related to the psychedelic experience.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111251"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylone regulates fear memory and amygdala activity: A potential treatment for posttraumatic stress disorder?","authors":"Dylan Chou ,&nbsp;Hsien-Yu Peng ,&nbsp;Tzer-Bin Lin ,&nbsp;Ming-Chun Hsieh ,&nbsp;Cheng-Yuan Lai ,&nbsp;Chau-Shoun Lee","doi":"10.1016/j.pnpbp.2024.111201","DOIUrl":"10.1016/j.pnpbp.2024.111201","url":null,"abstract":"<div><div>Methylone (3,4-methylenedioxy-<em>N</em>-methylcathinone) is a rapid-acting entactogen that has demonstrated significant benefits for patients with post-traumatic stress disorder (PTSD) and exhibits good tolerability in phase 1 clinical trials. Despite these promising results, its preclinical effects on fear memory regulation and the underlying mechanisms remain largely unexplored. This study aims to investigate the impact of methylone on auditory fear extinction and its influence on neuronal and synaptic activity in the basolateral amygdala (BLA). Using C57BL/6 mice, we employed an auditory fear conditioning paradigm along with immunofluorescent staining, extracellular electrophysiological recording, and chemogenetic techniques. The results revealed that administering methylone at a dosage of 10 mg/kg, in conjunction with extinction trials, significantly decreased the retrieval of both recent and remote fear memories. Additionally, methylone effectively inhibited the renewal of remote fear memories and blocked spontaneous recovery. It also reduced fear generalization to both context and tone. At the cellular level, methylone increased c-fos expression in the BLA and induced sustained elevations in long-term potentiation and long-term depression at the synaptic level. Furthermore, intra-BLA microinfusion of methylone directly enhanced the extinction memory. Chemogenetic activation of the BLA mimicked the effects of methylone, whereas chemogenetic inhibition blocked them. These findings suggest that methylone modulates fear memories through its action on the BLA. This preclinical study offers a knowledge base and critical insights into the potential future application of methylone for PTSD treatment.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111201"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arousal-promoting effect of the parabrachial nucleus and the underlying mechanisms: Recent advances","authors":"Yang-An Li ,&nbsp;Juan Yao ,&nbsp;Xuan Li ,&nbsp;Ke-Hui Hu","doi":"10.1016/j.pnpbp.2024.111226","DOIUrl":"10.1016/j.pnpbp.2024.111226","url":null,"abstract":"<div><div>The parabrachial nucleus (PBN) is responsible for integrating both internal and external sensory information and controlling/regulating a wide range of physiological processes, such as feeding, thermogenesis, nociceptive and pruritic sensations, and respiration. Recently, the PBN has been found to be involved in mediating wakefulness maintenance, sleep-wake transition, exogenous neuromodulation of awakening, and arousal-promoting process triggered by drastic changes in the internal environments, such as hypercapnia, hypoxia, and hypertension. Multiple neural pathways and subpopulations of neurons are responsible for arousal-promoting effects of the PBN. The medial PBN seems to be more important for the maintenance of physiological arousal, while the lateral PBN are more crucial in mediating interoception-driven arousal. Glutamatergic projection from the PBN to the basal forebrain (BF) and GABAergic projection from the BF to the cerebral cortex GABAergic neurons are the most pivotal neural pathways for awareness-promotion. Here, we review the relevant literature in this field in recent years and emphasize the potential prospects of PBN stimulation in translational medicine for the rehabilitation of disorders of consciousness.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111226"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 personality traits and life stress in alcohol use disorder: Insights from NGF gene polymorphisms of Han Chinese population in Taiwan","authors":"Shin-Chang Kuo ,&nbsp;Chun-Long Lin ,&nbsp;Yi-Wei Yeh ,&nbsp;Chun-Yen Chen ,&nbsp;Yu-Chieh Huang ,&nbsp;Ting-Yu Chang ,&nbsp;You-Ping Yang ,&nbsp;Jhih-Syuan Huang ,&nbsp;Bao-Zhu Yang ,&nbsp;San-Yuan Huang","doi":"10.1016/j.pnpbp.2024.111232","DOIUrl":"10.1016/j.pnpbp.2024.111232","url":null,"abstract":"<div><h3>Objective</h3><div>Alcohol use disorder (AUD) is a complex neuropsychiatric condition influenced by genetic and environmental factors. Nerve growth factor (NGF) plays a crucial role in neuronal neuroplasticity and chronic alcohol consumption may alter NGF levels in specific brain regions. The study investigates the associations between <em>NGF</em> gene polymorphisms, susceptibility to AUD, and specific stress and personality characteristics.</div></div><div><h3>Methods</h3><div>Our study involved 1133 participants from a homogeneous Han Chinese population, 587 of whom had AUD and 546 were controls. To minimize potential confounding factors, the AUD group was stratified by sex and age at baseline. A total of 414 participants completed the Life Event Questionnaires (LEQ), while 559 participants completed the Tridimensional Personality Questionnaire (TPQ).</div></div><div><h3>Results</h3><div>The <em>NGF</em>'s rs7523654 and rs11102929 loci were significantly associated with AUD, especially in female subgroups. Additional haplotype research confirmed similar findings. AUD patients showed more vital propensities for novelty seeking (NS) and harm avoidance (HA) compared to controls. Additionally, they recorded higher negative LEQ results. Notably, HA and negative LEQ scores among AUD people were significantly affected by the SNP rs11102929 in the <em>NGF</em> gene. The age at which AUD first manifested and NS scores showed a reverse link, suggesting that a higher NS characteristic may predispose people to develop AUD earlier in life.</div></div><div><h3>Conclusion</h3><div>The findings suggest that the <em>NGF</em> gene may influence AUD susceptibility and its links to personality traits and life stress. However, the small sample of women with AUD limits the reliability of these associations, highlighting the need for further study.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111232"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors impacting prazosin efficacy for nightmares and insomnia in PTSD patients - a systematic review and meta-regression analysis","authors":"Thaís Pereira Mendes ,&nbsp;Brunno Guimarães Pereira ,&nbsp;Evandro Silva Freire Coutinho ,&nbsp;Marina S. Melani ,&nbsp;Thomas C. Neylan ,&nbsp;William Berger","doi":"10.1016/j.pnpbp.2025.111253","DOIUrl":"10.1016/j.pnpbp.2025.111253","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD) is a debilitating condition affecting 5.7 % of the global population in their lifetime. There is a strong association between trauma-related nightmares and insomnia with higher rates of physical illness, mental distress, and suicide among PTSD patients. Prazosin, an α1-adrenergic antagonist, has shown mixed results in treating these sleep disturbances. This study aims to evaluate the effect of prazosin compared to placebo on insomnia, nightmares, and global PTSD symptoms, and to examine variables that might influence this effect. We conducted a meta-analysis and a novel meta-regression analysis of randomized clinical trials (RCTs) comparing prazosin to placebo in samples of patients with PTSD. Data sources were MEDLINE, EMBASE, Scopus, ISI Web of Science, and PTSD Pubs. Examined variables were age, gender, military/civilian status, prazosin dose, treatment duration, baseline symptom severity, use of antidepressants, use of benzodiazepines (BDZ), prevalence of depression, and alcohol use disorder. Ten RCTs with 648 patients were included. Analysis revealed prazosin significantly improved insomnia (SMD = −0.654, <em>p</em> = 0.043) and nightmares (SMD = −0.641, <em>p</em> = 0.025), but not overall PTSD symptoms (SMD = −0.428, <em>p</em> = 0.077). Unexpectedly, higher BDZ use was associated with greater improvement in insomnia (β = −0.046; <em>p</em> = 0.01) and PTSD severity (β = −0.037; <em>p</em> = 0.004). These findings suggest that prazosin effectively reduces insomnia and nightmares in PTSD patients. Benzodiazepine co-administration seems to enhance prazosin's efficacy, suggesting that the addition of prazosin might allow for a reduction of BDZ doses in these patients. Further research should empirically test the efficacy of prazosin alone versus prazosin combined with BDZ to confirm these findings.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111253"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemistry to cognition: Therapeutic potential of (m-CF₃-PhSe)₂ targeting rats' striatum dopamine proteins in amphetamine dependence.","authors":"Mustafa Munir Mustafa Dahleh, Sabrina Grendene Muller, Isabella Pregardier Klann, Luiza Souza Marques, Jéssica Leandra da Rosa, Murilo Barboza Fontoura, Marilise Escobar Burger, Cristina Wayne Nogueira, Marina Prigol, Silvana Peterini Boeira, Hecson Jesser Segat","doi":"10.1016/j.pnpbp.2024.111238","DOIUrl":"10.1016/j.pnpbp.2024.111238","url":null,"abstract":"<p><p>Amphetamine (AMPH) abuse represents a major global public health issue, highlighting the urgent need for effective therapeutic interventions to manage addiction caused by this psychostimulant. This study aimed to assess the potential of m-trifluoromethyl-diphenyldiselenide [(m-CF₃-PhSe)₂] in preventing the addictive effects induced by AMPH through targeting dopamine metabolism proteins. (m-CF₃-PhSe)₂ is of interest due to its demonstrated efficacy in mitigating opioid abuse, establishing it as a promising candidate for addiction treatment research. Initially, in silico studies examined the affinity of AMPH and (m-CF₃-PhSe)₂ for dopamine 1, 2, and 3 receptors (D1R, D2R, D3R), and dopamine transporter (DAT). In our experimental design, male Wistar rats were divided into four groups: I) Control; II) (m-CF₃-PhSe)₂; III) AMPH; IV) (m-CF₃-PhSe)₂ + AMPH. Animals were administered (m-CF₃-PhSe)₂ (0.1 mg/kg, by gavage) or canola oil (vehicle) 30 min before AMPH (4.0 mg/kg, i.p.) administration. Drug administration occurred for 8 days in the conditioned place preference (CPP) paradigm. Twenty-four hours after the last CPP conditioning section, preference for the drug-compartment was assessed, with anxiety-related effects and working memory were evaluated using the Y-maze test. Finally, animals were euthanized for striatal dissection to quantify D1R, D2R, D3R, and DAT levels in western blot. In silico findings suggest that (m-CF₃-PhSe)₂ may prevent AMPH activation in DAT, interacting with Asp46 and Phe319, preventing possible addictive effects of AMPH in DAT. In vivo results showed that (m-CF₃-PhSe)₂ attenuated AMPH effects, reducing preference for the drug-compartment in CPP test. Furthermore, (m-CF₃-PhSe)₂ prevented AMPH-induced anxiogenic effects in the elevated plus maze (EPM) test, similarly to light/dark test. No differences in locomotion or working memory were observed among the experimental groups in the Y-maze test. Ex vivo western blot analyses of the entire striatum indicates that (m-CF₃-PhSe)₂ prevented the AMPH-induced increase in D1R levels and decrease in D2R and DAT levels, with no changes in D3R levels. Overall, our study suggests that (m-CF₃-PhSe)₂ may interact with DAT sites similarly to AMPH, reducing drug-compartment preference and anxiogenic behaviors while maintaining dopaminergic metabolism proteins in the striatum, a key region involved in the onset and perpetuation of addiction.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111238"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and preclinical evidence of psilocybin as antidepressant. A narrative review.","authors":"Ines Erkizia-Santamaría, Igor Horrillo, J Javier Meana, Jorge E Ortega","doi":"10.1016/j.pnpbp.2025.111249","DOIUrl":"10.1016/j.pnpbp.2025.111249","url":null,"abstract":"<p><p>In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered favourable, with low toxicity and good tolerance. Several preclinical studies have also been carried out to determine the long-term mechanism of action of this drug. In this sense, preclinical studies in naïve animals as well as in animal models of disease have shown somewhat discrepant results in conventional tests for assessment of depression- and anxiety-like phenotype in response to psilocybin, but overall suggest positive outcomes. Additionally, several valuable assays in rodent models have been developed over the years to elucidate the neurochemical correlates of serotonin 2A receptor (5HT2AR) activation in the brain, primary molecular target of psilocin. This review aims to provide a general overview of the current and most recent literature in the therapeutic potential of psilocybin through a description of clinical trials of psilocybin-assisted psychotherapy, and to showcase the scene in the up-to-date preclinical research. A detailed description of preclinical rodent models and experimental approaches that have been used to study the neurobiological and behavioural actions of psilocybin is provided, and potential therapeutic mechanisms of action are discussed.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111249"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}