International Journal of Neuropsychopharmacology最新文献

{"title":"Association of Prolactin, Oxytocin, and Homocysteine With the Clinical and Cognitive Features of a First Episode of Psychosis Over a 1-Year Follow-Up.","authors":"Maria Hidalgo-Figueroa, Alejandro Salazar, Cristina Romero-López-Alberca, Karina S MacDowell, Borja García-Bueno, Miquel Bioque, Miquel Bernardo, Mara Parellada, Ana González-Pinto, M Paz García-Portilla, Antonio Lobo, Roberto Rodriguez-Jimenez, Esther Berrocoso, Juan C Leza","doi":"10.1093/ijnp/pyad051","DOIUrl":"10.1093/ijnp/pyad051","url":null,"abstract":"<p><strong>Background: </strong>The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics.</p><p><strong>Methods: </strong>We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features.</p><p><strong>Results: </strong>At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients.</p><p><strong>Conclusion: </strong>This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"796-807"},"PeriodicalIF":4.8,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10029588","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":"Distinct Neural Representations and Cognitive Behaviors Attributable to Naturally Developed Active Avoidance or Reactive Escape Strategies in the Male Rat.","authors":"Liang Jing, Chen Ma, Lin Xu, Gal Richter-Levin","doi":"10.1093/ijnp/pyad054","DOIUrl":"10.1093/ijnp/pyad054","url":null,"abstract":"<p><strong>Background: </strong>The high individual variability in coping with stress is often attributed to genetic background differences, sustained environmental conditions, or a combination of both. However, the neural mechanisms underlying coping style variability are still poorly understood.</p><p><strong>Methods: </strong>Here we examined the impact of a single extended emotional challenge on coping style variability and the associated involvement of the hippocampus, medial prefrontal cortex (mPFC), and periaqueductal gray (PAG). Male Sprague-Dawley rats (n = 170) were trained in an extended 2-way shuttle avoidance (eTWSA) task for 7 days, and daily avoidance rates were measured. Forced swim test, elevated plus maze, or Morris water maze was tested before or after eTWSA exposure. Excitotoxic lesion of the hippocampal dentate gyrus (DG) was performed by Ibotenic infusion. Transient pharmacological blocking of DG, mPFC, or PAG was performed by muscimol or CNQX+TTX infusion.</p><p><strong>Results: </strong>Exposing rats to eTWSA was found to lead to naturally developing dichotomous, not continuous, coping styles, which we termed active avoidance (AA) or reactive escape (RE). Prior emotional responses did not predict the developing coping style. AA was associated with beneficial outcomes, including reduced behavioral despair and improved spatial learning. RE led to impaired spatial retrieval. AA was abolished by lesioning or pharmacological blocking of the DG. RE was prevented by blocking mPFC or PAG.</p><p><strong>Conclusion: </strong>The results indicate that a single exposure to a significant emotional challenge can lead, in otherwise healthy individuals, to dichotomous development of an active or reactive coping style with distinctive neural correlates and subsequent behavioral significance.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"761-772"},"PeriodicalIF":4.8,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41124279","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":"The Atypical Dopamine Transporter Inhibitor CE-158 Enhances Dopamine Neurotransmission in the Prefrontal Cortex of Male Rats: A Behavioral, Electrophysiological, and Microdialysis Study.","authors":"Claudia Sagheddu, Enzo Cancedda, Farshid Bagheri, Predrag Kalaba, Anna Lisa Muntoni, Jana Lubec, Gert Lubec, Fabrizio Sanna, Marco Pistis","doi":"10.1093/ijnp/pyad056","DOIUrl":"10.1093/ijnp/pyad056","url":null,"abstract":"<p><strong>Background: </strong>Dopamine plays a key role in several physiological functions such as motor control, learning and memory, and motivation and reward. The atypical dopamine transporter inhibitor S,S stereoisomer of 5-(((S)-((S)-(3-bromophenyl)(phenyl)methyl)sulfinyl)methyl)thiazole (CE-158) has been recently reported to promote behavioral flexibility and restore learning and memory in aged rats.</p><p><strong>Methods: </strong>Adult male rats were i.p. administered for 1 or 10 days with CE-158 at the dose of 1 or 10 mg/kg and tested for extracellular dopamine in the medial prefrontal cortex by means of intracerebral microdialysis and single unit cell recording in the same brain area. Moreover, the effects of acute and chronic CE-158 on exploratory behavior, locomotor activity, prepulse inhibition, working memory, and behavioral flexibility were also investigated.</p><p><strong>Results: </strong>CE-158 dose-dependently potentiated dopamine neurotransmission in the medial prefrontal cortex as assessed by intracerebral microdialysis. Moreover, repeated exposure to CE-158 at 1 mg/kg was sufficient to increase the number of active pyramidal neurons and their firing frequency in the same brain area. In addition, CE-158 at the dose of 10 mg/kg stimulates exploratory behavior to the same extent after acute or chronic treatment. Noteworthy, the chronic treatment at both doses did not induce any behavioral alterations suggestive of abuse potential (e.g., motor behavioral sensitization) or pro-psychotic-like effects such as disruption of sensorimotor gating or impairments in working memory and behavioral flexibility as measured by prepulse inhibition and Y maze.</p><p><strong>Conclusions: </strong>Altogether, these findings confirm CE-158 as a promising pro-cognitive agent and contribute to assessing its preclinical safety profile in a chronic administration regimen for further translational testing.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"784-795"},"PeriodicalIF":4.8,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41110672","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":"Schizophrenia Patients Discharged on Clozapine Plus Long-Acting Injectable Antipsychotics From a Public Psychiatric Hospital in Taiwan, 2006-2021.","authors":"Ta-Chun Lin, Ching-Hua Lin","doi":"10.1093/ijnp/pyad053","DOIUrl":"10.1093/ijnp/pyad053","url":null,"abstract":"Abstract Background Some schizophrenia patients treated with clozapine experience an inadequate response and adherence problems. The purpose of this study was to compare time to rehospitalization within 6 months in schizophrenia patients discharged on 3 clozapine regimens. Additionally, the temporal trend of prescription rate in each group was also explored. Methods Schizophrenia patients discharged from the study hospital from January 1, 2006, to December 31, 2021, (n = 3271) were included in the analysis. The type of clozapine prescribed at discharge was divided into 3 groups: clozapine plus long-acting injectable antipsychotics (clozapine + LAIs), clozapine plus other oral antipsychotics (clozapine + OAPs), and clozapine monotherapy. Survival analysis was used to compare time to rehospitalization within 6 months after discharge among the 3 groups. The temporal trend in the prescription rate of each group was analyzed using the Cochran-Armitage Trend test. Results Patients discharged on clozapine + LAIs had a significantly longer time to rehospitalization than those on clozapine + OAPs or clozapine monotherapy. The prescription rates of clozapine + LAIs and clozapine + OAPs significantly increased over time, whereas the prescription rates of clozapine monotherapy significantly decreased. Conclusions Compared with the clozapine + OAPs group, the clozapine + LAIs group had a lower risk of rehospitalization and a lower dose of clozapine prescribed. Therefore, if a second antipsychotic is required for patients who are taking clozapine alone, LAIs should be considered earlier.","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"808-816"},"PeriodicalIF":4.8,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10057296","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":"Longitudinal Impact of the COVID-19 Pandemic on Stress and Occupational Well-Being of Mental Health Professionals: An International Study.","authors":"Cary S Kogan, José A Garcia-Pacheco, Tahilia J Rebello, Madeline I Montoya, Rebeca Robles, Brigitte Khoury, Maya Kulygina, Chihiro Matsumoto, Jingjing Huang, María Elena Medina-Mora, Oye Gureje, Dan J Stein, Pratap Sharan, Wolfgang Gaebel, Shigenobu Kanba, Howard F Andrews, Michael C Roberts, Kathleen M Pike, Min Zhao, José Luis Ayuso-Mateos, Karolina Sadowska, Karen Maré, Keith Denny, Geoffrey M Reed","doi":"10.1093/ijnp/pyad046","DOIUrl":"10.1093/ijnp/pyad046","url":null,"abstract":"<p><strong>Background: </strong>Increased levels of occupational stress among health professionals during the COVID-19 pandemic have been documented. Few studies have examined the effects of the pandemic on mental health professionals despite the heightened demand for their services.</p><p><strong>Method: </strong>A multilingual, longitudinal, global survey was conducted at 3 time points during the pandemic among members of the World Health Organization's Global Clinical Practice Network. A total of 786 Global Clinical Practice Network members from 86 countries responded to surveys assessing occupational distress, well-being, and posttraumatic stress symptoms.</p><p><strong>Results: </strong>On average, respondents' well-being deteriorated across time while their posttraumatic stress symptoms showed a modest improvement. Linear growth models indicated that being female, being younger, providing face-to-face health services to patients with COVID-19, having been a target of COVID-related violence, and living in a low- or middle-income country or a country with a higher COVID-19 death rate conveyed greater risk for poor well-being and higher level of stress symptoms over time. Growth mixed modeling identified trajectories of occupational well-being and stress symptoms. Most mental health professions demonstrated no impact to well-being; maintained moderate, nonclinical levels of stress symptoms; or showed improvements after an initial period of difficulty. However, some participant groups exhibited deteriorating well-being approaching the clinical threshold (25.8%) and persistently high and clinically significant levels of posttraumatic stress symptoms (19.6%) over time.</p><p><strong>Conclusions: </strong>This study indicates that although most mental health professionals exhibited stable, positive well-being and low stress symptoms during the pandemic, a substantial minority of an already burdened global mental health workforce experienced persistently poor or deteriorating psychological status over the course of the pandemic.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"747-760"},"PeriodicalIF":4.5,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/6a/pyad046.PMC10586039.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9981225","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":"A Synthetic External Control Study Comparing the Clinical Efficacy of Wendan Decoction and 19 Antidepressants.","authors":"Yuting Yang,&nbsp;Rui Chen,&nbsp;Caixia Li,&nbsp;Qingshan Zheng,&nbsp;Yinghua Lv,&nbsp;Lujin Li,&nbsp;Hongsheng Tan","doi":"10.1093/ijnp/pyad044","DOIUrl":"10.1093/ijnp/pyad044","url":null,"abstract":"<p><strong>Background: </strong>Wendan decoction (WDD) has been used as a treatment for depression in China since the Tang Dynasty. However, high-quality evidence for this is lacking. This study proposed a novel synthetic external control method to evaluate its clinical efficacy.</p><p><strong>Methods: </strong>We searched public databases for clinical trials of WDD for major depression. The rate of change of the Hamilton Depression Scale score from baseline was used as an efficacy indicator, and a model-based meta-analysis was performed to analyze the clinical efficacy of WDD. To establish a reference standard for efficacy, the antidepressant efficacy distributions of a placebo and 19 antidepressants were virtually synthesized based on the same conditions as the clinical trial characteristics of WDD.</p><p><strong>Results: </strong>This study included 5 clinical trials with 177 participants. WDD showed a slow onset, with a time to reach the maximum effect of 9.71 weeks. At 8 weeks, the rate of change in the Hamilton Depression Scale score from baseline was 66.4% (95% CI = 62.3%-70.3%) in the WDD group. The pure effect value of WDD, after deducting the placebo effect, was 26.9% (95%CI = 23.0%-30.9%), which was comparable with 5 types of antidepressants and significantly higher than the others.</p><p><strong>Conclusion: </strong>The proposed external synthetic control method provides a solution to the bottleneck problem of clinical efficacy evaluation in real-world research on traditional Chinese medicine. WDD has high clinical development value for the treatment of depression, and large-scale randomized controlled trials are recommended to confirm its antidepressant effect.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"739-746"},"PeriodicalIF":4.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/5e/pyad044.PMC10586025.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10247903","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":"Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers.","authors":"Priyanka Singh,&nbsp;Ankit Srivastava,&nbsp;Debleena Guin,&nbsp;Sarita Thakran,&nbsp;Jyoti Yadav,&nbsp;Puneet Chandna,&nbsp;Mamta Sood,&nbsp;Rakesh Kumar Chadda,&nbsp;Ritushree Kukreti","doi":"10.1093/ijnp/pyad001","DOIUrl":"10.1093/ijnp/pyad001","url":null,"abstract":"<p><strong>Background: </strong>The clinical heterogeneity in major depressive disorder (MDD), variable treatment response, and conflicting findings limit the ability of genomics toward the discovery of evidence-based diagnosis and treatment regimen. This study attempts to curate all genetic association findings to evaluate potential variants for clinical translation.</p><p><strong>Methods: </strong>We systematically reviewed all candidates and genome-wide association studies for both MDD susceptibility and antidepressant response, independently, using MEDLINE, particularly to identify replicated findings. These variants were evaluated for functional consequences using different in silico tools and further estimated their diagnostic predictability by calculating positive predictive values.</p><p><strong>Results: </strong>A total of 217 significantly associated studies comprising 1200 variants across 545 genes and 128 studies including 921 variants across 412 genes were included with MDD susceptibility and antidepressant response, respectively. Although the majority of associations were confirmed by a single study, we identified 31 and 18 replicated variants (in at least 2 studies) for MDD and antidepressant response. Functional annotation of these 31 variants predicted 20% coding variants as deleterious/damaging and 80.6% variants with regulatory effect. Similarly, the response-related 18 variants revealed 25% coding variant as damaging and 88.2% with substantial regulatory potential. Finally, we could calculate the diagnostic predictability of 19 and 5 variants whose positive predictive values ranges from 0.49 to 0.66 for MDD and 0.36 to 0.66 for response.</p><p><strong>Conclusions: </strong>The replicated variants presented in our data are promising for disease diagnosis and improved response outcomes. Although these quantitative assessment measures are solely directive of available observational evidence, robust homogenous validation studies are required to strengthen these variants for molecular diagnostic application.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"692-738"},"PeriodicalIF":4.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10599097","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":"Inhibitory Neurons in Nucleus Tractus Solitarius Are Involved in Decrease of Heart Rate Variability and Development of Depression-Like Behaviors in Temporal Lobe Epilepsy.","authors":"Guliqiemu Aimaier,&nbsp;Kun Qian,&nbsp;Huateng Cao,&nbsp;Weifeng Peng,&nbsp;Zhe Zhang,&nbsp;Jing Ding,&nbsp;Xin Wang","doi":"10.1093/ijnp/pyad033","DOIUrl":"10.1093/ijnp/pyad033","url":null,"abstract":"<p><strong>Background: </strong>Diminished heart rate variability (HRV) has been observed in epilepsy, especially in epilepsy with depressive disorders. However, the underlying mechanism remains elusive.</p><p><strong>Methods: </strong>We studied HRV, spontaneous recurrent seizures, and depression-like behaviors in different phases of pilocarpine-induced temporal lobe epilepsy (TLE) in mice. Single-cell RNA sequencing analysis was used to identify various nerve cell subsets in TLE mice with and without depression. Differentially expressed gene (DEG) analysis was performed in epilepsy, depression, and HRV central control-related brain areas.</p><p><strong>Results: </strong>We found decreased HRV parameters in TLE mice, and alterations were positively correlated with the severity of depression-like behaviors. The severity of depression-like behaviors was correlated with the frequency of spontaneous recurrent seizure. Characteristic expression of mitochondria-related genes was significantly elevated in mice with depression in glial cells, and the enrichment analysis of those DEGs showed an enriched GABAergic synapse pathway in the HRV central control-related brain area. Furthermore, inhibitory neurons in the nucleus tractus solitarius, which is an HRV central control-related brain area, were specifically expressed in TLE mice combined with depression compared with those in mice without depression. A significantly enriched long-term depression pathway in DEGs from inhibitory neurons was found.</p><p><strong>Conclusions: </strong>Our study reported correlations between HRV and epilepsy-depression comorbidity in different phases of TLE. More importantly, we found that HRV central control-related inhibitory neurons are involved in the development of depression in TLE, providing new insights into epilepsy comorbid with depression.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"669-679"},"PeriodicalIF":4.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/5b/pyad033.PMC10586034.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760029","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":"Cucurbitacin B Exerts Significant Antidepressant-Like Effects in a Chronic Unpredictable Mild Stress Model of Depression: Involvement of the Hippocampal BDNF-TrkB System.","authors":"Jian-Bin Ge, Bo Jiang, Tian-Shun Shi, Wei-Yu Li, Wei-Jia Chen, Bao-Lun Zhu, Zheng-Hong Qin","doi":"10.1093/ijnp/pyad052","DOIUrl":"10.1093/ijnp/pyad052","url":null,"abstract":"<p><strong>Background: </strong>Although depression has been a serious neuropsychiatric disorder worldwide, current antidepressants used in clinical practice have various weaknesses, including delayed onset and low rates of efficacy. Recently, the development of new antidepressants from natural herbal medicine has become one of the important research hotspots. Cucurbitacin B is a natural compound widely distributed in the Cucurbitaceae and Cruciferae families and has many pharmacological activities. The present study aimed to investigate whether cucurbitacin B possess antidepressant-like effects in mice.</p><p><strong>Methods: </strong>The antidepressant-like effects of cucurbitacin B on mice behaviors were explored using the forced swim test, tail suspension test, open field test, sucrose preference test, and a chronic unpredictable mild stress model of depression together. Then, western blotting and immunofluorescence were used to examine the effects of cucurbitacin B on the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling cascade and neurogenesis in the hippocampus of mice. Furthermore, BDNF-short hairpin RNA, K252a, and p-chlorophenylalanine methyl ester were adopted together to determine the antidepressant mechanism of cucurbitacin B.</p><p><strong>Results: </strong>It was found that administration of cucurbitacin B indeed produced notable antidepressant-like effects in mice, which were accompanied with significant promotion in both the hippocampal BDNF-TrkB pathway and neurogenesis. The antidepressant mechanism of cucurbitacin B involves the hippocampal BDNF-TrkB system but not the serotonin system.</p><p><strong>Conclusions: </strong>Cucurbitacin B has the potential to be a novel antidepressant candidate.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"680-691"},"PeriodicalIF":4.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10388710","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":"Activation of mTORC1 Signaling Cascade in Hippocampus and Medial Prefrontal Cortex Is Required for Antidepressant Actions of Vortioxetine in Mice.","authors":"Wei-Yu Li,&nbsp;Tian-Shun Shi,&nbsp;Jie Huang,&nbsp;Yan-Mei Chen,&nbsp;Wei Guan,&nbsp;Bo Jiang,&nbsp;Cheng-Niu Wang","doi":"10.1093/ijnp/pyad017","DOIUrl":"10.1093/ijnp/pyad017","url":null,"abstract":"<p><strong>Background: </strong>Although thought of as a multimodal-acting antidepressant targeting the serotonin system, more molecules are being shown to participate in the antidepressant mechanism of vortioxetine. A previous report has shown that vortioxetine administration enhanced the expression of rapamycin complex 1 (mTORC1) in neurons. It has been well demonstrated that mTORC1 participates in not only the pathogenesis of depression but also the pharmacological mechanisms of many antidepressants. Therefore, we speculate that the antidepressant mechanism of vortioxetine may require mTORC1.</p><p><strong>Methods: </strong>Two mouse models of depression (chronic social defeat stress and chronic unpredictable mild stress) and western blotting were first used together to examine whether vortioxetine administration produced reversal effects against the chronic stress-induced downregulation in the whole mTORC1 signaling cascade in both the hippocampus and medial prefrontal cortex (mPFC). Then, LY294002, U0126, and rapamycin were used together to explore whether the antidepressant effects of vortioxetine in mouse models of depression were attenuated by pharmacological blockade of the mTORC1 system. Furthermore, lentiviral-mTORC1-short hairpin RNA-enhanced green fluorescence protein (LV-mTORC1-shRNA-EGFP) was adopted to examine if genetic blockade of mTORC1 also abolished the antidepressant actions of vortioxetine in mice.</p><p><strong>Results: </strong>Vortioxetine administration produced significant reversal effects against the chronic stress-induced downregulation in the whole mTORC1 signaling cascade in both the hippocampus and mPFC. Both pharmacological and genetic blockade of the mTORC1 system notably attenuated the antidepressant effects of vortioxetine in mice.</p><p><strong>Conclusions: </strong>Activation of the mTORC1 system in the hippocampus and mPFC is required for the antidepressant actions of vortioxetine in mice.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":"655-668"},"PeriodicalIF":4.8,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/68/pyad017.PMC10586031.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9257699","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}