International Journal of Neuropsychopharmacology最新文献

{"title":"Inhibition of hippocampal or thalamic inputs to the nucleus accumbens reverses stress-induced alterations in dopamine system function.","authors":"Hannah B Elam, Alexandra M McCoy, Angela M Boley, Olivia J Yang, Natalie I Belle, Daniel J Lodge","doi":"10.1093/ijnp/pyaf034","DOIUrl":"10.1093/ijnp/pyaf034","url":null,"abstract":"<p><strong>Background: </strong>Symptoms of psychosis are often observed in patients with post-traumatic stress disorder (PTSD) and are driven by aberrant regulation of the mesolimbic dopamine system. We have previously shown that targeting upstream brain regions that regulate dopamine neuron activity, the ventral hippocampus (vHipp), and paraventricular nucleus of the thalamus (PVT) maybe a novel approach to restore dopamine system function. The vHipp and PVT work in concert to regulate ventral tegmental area (VTA) dopamine neuron activity through a multisynaptic circuit that begins with inputs to the nucleus accumbens (NAc). Therefore, we hypothesized that inhibition of projections from either the vHipp or PVT to the NAc would reverse stress-induced alterations in dopamine system function.</p><p><strong>Methods: </strong>In this study, we induced stress-related pathophysiology in rats using a 2-day inescapable foot shock procedure. We then examined if foot shock stress altered the firing patterns and coordinated neuronal activity within vHipp and PVT circuits. Finally, we examined if chemogenetic inhibition of NAc afferents could reverse stress-induced alterations in dopamine system function.</p><p><strong>Results: </strong>We observed a significant increase in coherence between the PVT and NAc up to 48 hours after foot shock stress. In addition, stress increased VTA dopamine neuron population activity, which was reversed following chemogenetic inhibition of either vHipp-NAc or PVT-NAc projections.</p><p><strong>Conclusions: </strong>Taken together, these results suggest that increased coherence between the PVT and NAc, following stress, may contribute to psychosis-like symptoms but targeting either the PVT or vHipp may be viable options for the treatment of comorbid psychosis related to PTSD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study.","authors":"Naim Zaki, Li Nancy Chen, Rosanne Lane, Teodora Doherty, Wayne C Drevets, Randall L Morrison, Gerard Sanacora, Samuel T Wilkinson, Allan H Young, Acioly L T Lacerda, Jong-Woo Paik, Vanina Popova, Dong-Jing Fu","doi":"10.1093/ijnp/pyaf027","DOIUrl":"10.1093/ijnp/pyaf027","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;The rates of relapse and suicide risk are higher in treatment-resistant depression (TRD) vs non-treatment-resistant major depressive disorder. Even among patients with TRD who initially respond, the majority (70%) relapse within 6 months.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To evaluate the long-term safety and efficacy of esketamine nasal spray, combined with an oral antidepressant, in patients with TRD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Phase 3, open-label, single-arm long-term extension study (SUSTAIN-3) conducted from June 2016 to December 2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Outpatient.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;Adults with TRD who participated in ≥1 of 6 phase 3 \"parent\" studies continued esketamine by either entering a 4-week induction phase followed by an optimization/maintenance phase of variable duration (n = 458) or directly entering the optimization/maintenance phase of SUSTAIN-3 (n = 690), based on their individual response to study drug at the endpoint of the parent study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;Intranasal esketamine dosing was flexible, twice-weekly during induction and individualized to depression severity during optimization/maintenance (weekly, every-other-week, or every-4-weeks), under direct supervision by site staff.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;To assess the long-term safety of esketamine. Efficacy endpoints included the change in depressive symptoms, assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 1148 patients were enrolled. Total exposure to esketamine was 3777 cumulative patient-years. Mean (median, range) exposure to esketamine in SUSTAIN-3 was 42.9 (45.8, range 0-79) months. The most common adverse events were headache (36.9%), dizziness (33.9%), nausea (33.6%), dissociation (25.5%), nasopharyngitis (23.8%), somnolence (23.1%), dysgeusia (20.2%), and back pain (20.0%). During the study, 5.3% and 6.4% of participants discontinued due to lack of efficacy or adverse event, respectively. Nine participants died: COVID-19-related (n = 3), pneumonia (n = 2), and completed suicide, myocardial infarction, multiple injuries, unknown cause (n = 1 each). The mean MADRS total score decreased during induction, and this reduction persisted during optimization/maintenance (mean [SD] change from baseline-to-phase endpoint of each phase: induction: -12.8 [9.73]; optimization/maintenance: + 0.2 [9.93]). A total of 35.6% of participants were in remission at the induction endpoint, and 48.5% and 49.6% at week 112 and optimization/maintenance endpoint, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;In the SUSTAIN-3 final dataset, no new safety signals were identified during long-term treatment with intermittently-dosed esketamine, combined with oral antidepressant, and improvement in depression generally persisted among participants who remained on maintenance treatment. These results add ","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roluperidone monotherapy, a treatment for negative symptoms in schizophrenia.","authors":"Michael Davidson, Nadine Noel, Florent Schmitt, Remy Luthringer","doi":"10.1093/ijnp/pyaf032","DOIUrl":"10.1093/ijnp/pyaf032","url":null,"abstract":"<p><p>Roluperidone is a drug in development targeting primary negative symptoms in schizophrenia, which binds sigma-2, 5-HT2A, and alpha1a receptors. Roluperidone administered as monotherapy to patients suffering from mild to moderate negative symptoms and withdrawal from antipsychotic drugs, improved negative symptoms in 2 clinical trials. The patients who were symptomatically stable for 3 or 6 months before antipsychotic drug withdrawal showed a very low rate of psychotic symptoms worsening over 6 or 9-month trial duration. Focus: Treatment of primary negative symptoms in a subgroup of patients suffering from schizophrenia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological modulation of directed network communication and neural hubs in action-effect integration.","authors":"Jasmin Mayer, Anna Helin Koyun, Moritz Mückschel, Veit Roessner, Bernhard Hommel, Christian Beste","doi":"10.1093/ijnp/pyaf031","DOIUrl":"10.1093/ijnp/pyaf031","url":null,"abstract":"<p><strong>Background: </strong>Acting intentionally requires individuals to anticipate the effects of their actions. Recent work has revealed the neural oscillatory dynamics underlying the establishment of action-effect bindings, which are vital to anticipating action effects. However, the neurobiological basis of these processes is elusive.</p><p><strong>Methods: </strong>Healthy adult participants (N = 54) engaged in a double-blind, counter-balanced, placebo-controlled experiment in which they worked in an experiment able to examine how action effects are planned, anticipated, and processed under placebo and methylphenidate conditions. Electroencephalogram data were analyzed to investigate the directed communication in cortical networks underlying action effect integration.</p><p><strong>Results: </strong>We show that an increase in catecholaminergic system activity alters the strength of directed communication in a cortical theta frequency network constituted by the insular cortex, the anterior temporal lobe, and the inferior frontal cortex. Additionally, pharmacological modulation regulates which of the brain structures act as a hub in different phases of the action-effect binding process.</p><p><strong>Conclusions: </strong>The findings highlight how the neural organization of processes supporting intentional action can be optimized neurobiologically through the catecholaminergic system.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular targets of vortioxetine mediating glioblastoma suppression revealed by gene and protein network analyses and molecular docking simulations.","authors":"Chuanjun Zhuo, Chao Li, Qiuyu Zhang, Lei Yang, Ying Zhang, Ximing Chen, Xiaoyan Ma, Ranli Li, Lina Wang, Hongjun Tian","doi":"10.1093/ijnp/pyaf029","DOIUrl":"10.1093/ijnp/pyaf029","url":null,"abstract":"<p><strong>Background: </strong>Vortioxetine is a serotonin reuptake inhibitor and serotonin receptor modulator used for the treatment of major depressive disorder, but recent studies have also reported anticancer effects in models of glioblastoma. Given the well-established benefits of drug repositioning, we examined the pharmacological mechanism for these anticancer actions using bioinformatics and molecular docking.</p><p><strong>Methods: </strong>Putative molecular targets for vortioxetine were identified by searching DrugBank, GeneCards, SwissTargetPrediction, Comparative Toxicogenomics Database, and SuperPred databases, while glioblastoma-related proteins were identified using GeneCards, Online Mendelian Inheritance in Man; , and Therapeutic Target Database . A protein-protein interaction (PPI) network was constructed from vortioxetine targets also involved in glioblastoma to identify core (hub) targets, which were then characterized by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using database for annotation, visualization, and integrated discovery. Cytoscape was utilized to generate a drug-pathway-target-disease network, and molecular docking simulations were performed to evaluate direct interactions between vortioxetine and core target proteins.</p><p><strong>Results: </strong>A total of 234 unique vortioxetine protein targets were identified. Among 234 vortioxetine targets identified, 48 were also related to glioblastoma. Topological analysis of the PPI network revealed 5 core targets: the serine/threonine kinase AKT1, transcription factor hypoxia-inducible factor (HIF)-1, cell adhesion molecule cadherin-E, NF-κB subunit p105, and prostaglandin-endoperoxide synthase 2. According to GO and KEGG pathway analyses, the anticancer efficacy of vortioxetine may be mediated by effects on glucose metabolism, cell migration, phosphorylation, inflammatory responses, apoptosis, and signaling via Rap1, chemical carcinogenesis-reactive oxygen species, and HIF-1. Molecular docking revealed moderately strong affinities between vortioxetine and 4 core targets.</p><p><strong>Conclusions: </strong>This study suggests that vortioxetine may inhibit glioblastoma development through direct effects on multiple targets and further emphasizes the value of bioinformatics analyses for drug repositioning.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Risk of Adverse Drug Events in Combination with antiparkinsonics and antipsychotics - a two-decade real-world pharmacovigilance analysis based on the FAERS database.","authors":"Junyi Wang, Sen Lin, Chen Bai, Huimin Zhang, Haoqi Liu, Min Wang, Rongjuan Guo","doi":"10.1093/ijnp/pyaf033","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf033","url":null,"abstract":"<p><strong>Background: </strong>The combination of antiparkinsonics and antipsychotic drugs (AP) can improve the motor and mental symptoms of Parkinson's disease (PD) and reduce the actual burden of chronic disease care. To explore the adverse drug events (ADEs) worthy of attention in this treatment management process, we conducted a real-world pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database.</p><p><strong>Method: </strong>The Standard pharmacotherapy for PD include Levodopa/Carbidopa, Entacapone, Rasagiline, Pramipexole, Ropinirole, Rotigotine, Apomorphine and Amantadine, etc. AP includes Quetiapine, Clozapine and Pimavanserin. We collected the ADEs reports of FAERS that conformed to the combination regimens of anti-Parkinson's drugs and AP during the 20-year period from the third quarter of 2004 to the second quarter of 2024. Disproportionate analysis and subgroup analysis were conducted through five algorithms, namely Ω shrinkage measure, additive model, multiplicative model, Combination risk ratio, and Chi-square. The Time to onset (TTO) analysis was used to predict the variation of the risk size of ADEs occurrence over time. Finally, we explored the correlation between population characteristics and the occurrence of ADEs through Logistic regression.</p><p><strong>Result: </strong>We collected a total of 6,297 cases, including 38,316 ADEs records. The results of the disproportionate analysis show that The ADEs with the highest occurrence frequency include hallucination, general physical health deterioration, somnolence, stoma site discharge, urinary tract infection and memory impairment, etc. The TTO analysis results showed that the median TTO for all ADEs was 657.50 days, the median TTO for infection and inflammation was 716.00 days, and the median TTO for psychiatric symptoms was 823.00 days. All median TTOs conform to the early failure curve. The results of Logistic regression showed that gender was correlated with the occurrence of infection and inflammation, and the female population was more inclined to have IME related to infection and inflammation.</p><p><strong>Conclusion: </strong>During the combined application of antiparkinsonics and AP, in addition to ADEs such as movement disorders and emerging mental symptoms, the risks of infection and inflammation should also be given key attention. Long-term follow-up should run through the entire process of disease diagnosis and treatment, and attention should be paid to the influence of drug dosage forms and dosages. The medication plan should be adjusted in a timely manner when ADEs occur.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110712","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":"Premorbid characteristics of the SAPAP3 mouse model of obsessive-compulsive disorder: behavior, neuroplasticity, and psilocybin treatment.","authors":"Michal Lazar, Michal Brownstien, Alexander Botvinnik, Chloe Shevakh, Orr Shahar, Tzuri Lifschytz, Bernard Lerer","doi":"10.1093/ijnp/pyaf022","DOIUrl":"10.1093/ijnp/pyaf022","url":null,"abstract":"<p><strong>Background: </strong>SAPAP3-knockout (SAPAP3-KO) mice develop excessive self-grooming behavior at 4-6 months of age, serving as a model for obsessive-compulsive disorder (OCD). Given that anxiety often precedes OCD diagnosis in humans, this study investigated whether juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the self-grooming phenotype, and whether such behaviors respond to psilocybin (PSIL) treatment. The study also examined 4 key neuroplasticity-related synaptic proteins-GAP43, PSD95, synaptophysin, and SV2A-as SAPAP3 is a postsynaptic scaffold protein that interacts with PSD95 and may affect synaptic function.</p><p><strong>Methods: </strong>Two studies were conducted using male and female juvenile (10-13 weeks) SAPAP3-KO mice. Study 1 compared behavioral phenotypes between homozygous (HOM), heterozygous, and wild-type (WT) mice. Study 2 evaluated a different sample of HOM and WT mice and assessed the effect of PSIL (4.4 mg/kg) on identified behavioral differences. Both studies included comprehensive behavioral testing focused on anxiety-like behavior, social interaction, and cognitive function. Additionally, levels of 4 synaptic proteins were measured by western blots in the frontal cortex, hippocampus, amygdala, and striatum of juvenile and adult SAPAP3-KO mice.</p><p><strong>Results: </strong>In both studies, juvenile HOM SAPAP3-KO mice showed significant anxiety-like behaviors compared to WT mice, spending less time in open field center, and elevated plus maze open arms. They also buried fewer marbles and found fewer buried Oreos than WT mice. Psilocybin treatment did not improve these behavioral manifestations. Analysis of synaptic proteins revealed significant increases in GAP43, synaptophysin, and SV2A across multiple brain regions in adult male HOM mice and of SV2A in the frontal cortex of HOM females compared to WT, but not in juvenile mice of either sex.</p><p><strong>Conclusions: </strong>Juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the characteristic excessive self-grooming phenotype, paralleling the prodromal anxiety often seen in human OCD. Unlike in adult SAPAP3-KO mice, these manifestations were not responsive to PSIL treatment. The age-dependent increases in synaptic proteins observed in adult (but not juvenile) male SAPAP3-KO mice HOM for the deletion and to a lesser extent in female homozygotes, may represent compensatory plasticity changes in response to the phenotype. These results provide insights into the developmental trajectory of OCD-like behaviors and associated neuroplastic adaptations.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of relapse with all-cause mortality in adult patients with stable schizophrenia.","authors":"Christoph U Correll, Brahim K Bookhart, Carmela Benson, Zhiwen Liu, Zhongyun Zhao, Wenze Tang","doi":"10.1093/ijnp/pyaf018","DOIUrl":"10.1093/ijnp/pyaf018","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia shortens the average lifespan by an estimated 15 years. This retrospective study evaluated whether relapse independently increases all-cause mortality risk in patients with stable schizophrenia.</p><p><strong>Methods: </strong>Eligible adults had ≥2 outpatient claims on separate dates or ≥1 inpatient claim with a schizophrenia diagnosis code, had ≥12 months of continuous pre-index enrollment without a relapse, and received ≥1 antipsychotic medication during the baseline period. Occurrence and number of inpatient and non-inpatient relapses and all-cause mortality were evaluated during follow-up. A marginal structural model adjusting for both baseline and time-varying confounding was used to estimate hazard ratios (HRs) and 95% CIs.</p><p><strong>Results: </strong>Mean age at index of the 32 071 patients included in the analysis was 57.6 (SD, 15.3) years; 51.0% of patients were male and 55.4% were White. During a mean follow-up of 40 (range, 1-127) months, 3974 (12.4%) patients died. Of the 9170 (28.6%) patients with relapse(s) during follow-up, most experienced 1 (53.4%) or 2 (20.0%) relapses. After adjustment for covariates, the HR for all-cause mortality was significantly higher for patients with 1 relapse vs no relapses (1.20 [95% CI, 1.14-1.26]). For the first 5 relapses, each subsequent relapse increased all-cause mortality hazard by approximately 20%. Estimated 5-year survival was 78% in patients with 1 relapse and 58% in patients with 10 relapses.</p><p><strong>Conclusions: </strong>The observed increase in all-cause mortality associated with schizophrenia relapse underscores the need for heightened attention to relapse prevention, including greater utilization of effective treatment strategies early in the course of disease.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sedative and hypnotic effects of nuciferine: enhancing rodent sleep via serotonergic system modulation.","authors":"Luo-Xuan Wang, Yu-Meng Liu, Yong-Fang Gu, Lu Li, Ren-Hong Qiu, Yan-Kai Wang, Jin Yang, Ji Wang, Yang Zhang, Shuo Li, Qiong-Yin Fan, Rui Xue, Jing-Cao Li, You-Zhi Zhang","doi":"10.1093/ijnp/pyaf019","DOIUrl":"10.1093/ijnp/pyaf019","url":null,"abstract":"<p><strong>Background: </strong>Insomnia is the most prevalent sleep disorder globally. Nuciferine (NF), a bioactive constituent extracted from Nelumbo nucifera leaves, is recognized for its diverse pharmacological activities. However, its sleep-regulating effects have not been investigated. This study aimed to delineate the therapeutic effects and underlying mechanisms of NF in mitigating insomnia.</p><p><strong>Methods: </strong>The sedative-hypnotic effects of NF were assessed employing locomotor activity test, pentobarbital-induced sleep test, and electroencephalography-based sleep profiling. Insomnia symptoms in rodents were induced by serotonin (5-HT) depletion and environmental stress. The potential mechanisms of NF's action through the regulation of central serotonin system were also explored.</p><p><strong>Results: </strong>Nuciferine attenuated locomotor activity and extended pentobarbital-induced sleep duration in a dose-dependent manner. It also significantly augmented total and non-rapid eye movement (NREM) sleep time and enhanced delta power at frequencies of 0.5 and 1 Hz in normal rats. Sleep analysis revealed that NF effectively reversed the reduction in total and NREM sleep time caused by environmental stress from cage changing. NF treatment also proved effective against insomnia induced by 5-HT depletion, as evidenced by increased sleep duration and reduced sleep latency. Further investigation revealed a synergetic effect of NF and 5-hydroxytryptophan, alone with increased 5-HT and 5-HT1A receptor levels in the hypothalamus of insomniac mice following NF administration.</p><p><strong>Conclusions: </strong>The results demonstrate NF's hypnotic effects and its ability to alleviate insomnia, providing preclinical evidence for its potential as a naturally derived treatment for insomnia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cigarette smoking is associated with levels of the serotonin transporter in the brain: a [11C]DASB PET Study.","authors":"Paul Faulkner, Gitte M Knudsen, Vibe G Frokjaer, David Erritzoe","doi":"10.1093/ijnp/pyaf026","DOIUrl":"10.1093/ijnp/pyaf026","url":null,"abstract":"<p><strong>Background: </strong>Preclinical work suggests that chronic nicotine/tobacco use is associated with reductions in serotonin within the hippocampus, yet no research has yet shown an association of smoking behaviors and alterations in brain serotonin in humans in vivo.</p><p><strong>Methods: </strong>We therefore analyzed existing [11C]DASB PET data from the Cimbi Database to compare the availability of the serotonin transporter (SERT) in the hippocampus, midbrain (including the raphe), and neocortex of 60 healthy non-smokers, 15 ex-smokers, and 11 current smokers who also provided blood samples for determination of plasma tryptophan load. Because SERT availability is considered to be negatively associated with extracellular serotonin levels, we hypothesized that current smokers would exhibit greater SERT availability than ex-smokers and non-smokers.</p><p><strong>Results: </strong>There was a significant main effect of group on SERT binding (DASB BPND) values in the bilateral and left hippocampus, and a trend toward such in the right hippocampus. Post hoc ANOVAs revealed that current smokers exhibited greater hippocampal DASB BPND than both non-smokers and ex-smokers, while the latter 2 groups did not differ. There were no group effects on DASB BPND within the midbrain or global neocortex. Finally, there was no significant group effect on plasma tryptophan load.</p><p><strong>Conclusions: </strong>This study provides the first in vivo evidence that current smoking may be associated with elevated hippocampal SERT binding-possibly reflecting lower synaptic serotonin concentrations, and that this change may normalize following smoking cessation.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}