International Journal of Neuropsychopharmacology最新文献

{"title":"Thrombomodulin Improves Cognitive Deficits in Heat-Stressed Mice.","authors":"Cheng-Hsien Lin, Ling-Yu Tang, Lin-Yu Wang, Ching-Ping Chang","doi":"10.1093/ijnp/pyae027","DOIUrl":"10.1093/ijnp/pyae027","url":null,"abstract":"<p><strong>Background: </strong>Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed (HS) mice.</p><p><strong>Methods: </strong>Adult male mice were exposed to HS (33°C for 2 hours daily for 7 consecutive days) to induce cognitive deficits. Recombinant human soluble TM (1 mg/kg, i.p.) was administered immediately after the first HS trial and then once daily for 7 consecutive days. We performed the Y-maze, novel objective recognition, and passive avoidance tests to evaluate cognitive function. Plasma levels of lipopolysaccharide (LPS), high-mobility group box 1 (HMGB1), coagulation parameters, and both plasma and tissue levels of inflammatory and oxidative stress markers were biochemically measured. The duodenum and hippocampus sections were immunohistochemically stained. The intestinal and blood-brain barrier permeability were determined.</p><p><strong>Results: </strong>Compared with controls, HS mice treated with TM had lesser extents of cognitive deficits, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory, oxidative, and coagulatory injury to heart, duodenum, and hippocampal tissues, and increased plasma HMGB1. In addition to reducing cognitive deficits, TM therapy alleviated all the abovementioned complications in heat-stressed mice.</p><p><strong>Conclusions: </strong>The findings suggest that HS can lead to exacerbated stress reactions, endotoxemia, gut barrier disruption, blood-brain barrier disruption, hippocampal inflammation, coagulopathy, and oxidative stress, which may act as causative factors for cognitive deficits. TM, an anti-inflammatory, antioxidant, and anti-coagulatory agent, inhibited heat stress-induced cognitive deficits in mice.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11259854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467867","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":"Antipsychotics, COVID-19, and Secondary Healthcare Databases: Revisiting the Pandemic.","authors":"Xavier Boland, Luiz Dratcu","doi":"10.1093/ijnp/pyae026","DOIUrl":"10.1093/ijnp/pyae026","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327505","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":"Understanding the Therapeutic Action of Antipsychotics: Not yet Beyond Striatal Dopamine? A Comment on Direktor et al. (2024).","authors":"Gavin P Reynolds","doi":"10.1093/ijnp/pyae028","DOIUrl":"10.1093/ijnp/pyae028","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11237989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491890","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":"Divergent Roles of APOAI and APOM in the Identification of Alcohol Use Disorder and Their Association With Inflammation and Cognitive Decline: A Pilot Study.","authors":"Berta Escudero, Leticia López-Valencia, Francisco Arias Horcajadas, Laura Orio","doi":"10.1093/ijnp/pyae029","DOIUrl":"10.1093/ijnp/pyae029","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorder (AUD) courses with inflammation and cognitive decline. Apolipoproteins have emerged as novel target compounds related to inflammatory processes and cognition.</p><p><strong>Methods: </strong>A cross-sectional study was performed on abstinent AUD patients with at least 1 month of abstinence (n  = 33; 72.7% men) and healthy controls (n  = 34; 47.1% men). A battery of plasma apolipoproteins (APOAI, APOAII, APOB, APOCII, APOE, APOJ, and APOM), plasma inflammatory markers (LPS, LBP), and their influence on cognition and presence of the disorder were investigated.</p><p><strong>Results: </strong>Higher levels of plasma APOAI, APOB, APOE, and APOJ, as well as the proinflammatory LPS, were observed in the AUD group, irrespective of sex, whereas APOM levels were lower vs controls. Hierarchical logistic regression analyses, adjusting for covariates (age, sex, education), associated APOM with the absence of cognitive impairment in AUD and identified APOAI and APOM as strong predictors of the presence or absence of the disorder, respectively. APOAI and APOM did not correlate with alcohol abuse variables or liver status markers, but they showed an opposite profile in their associations with LPS (positive for APOAI; negative for APOM) and cognition (negative for APOAI; positive for APOM) in the entire sample.</p><p><strong>Conclusions: </strong>The HDL constituents APOAI and APOM were differentially regulated in the plasma of AUD patients compared with controls, playing divergent roles in the disorder identification and associations with inflammation and cognitive decline.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544752","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":"Subanesthetic Ketamine Suppresses Locus Coeruleus-Mediated Alertness Effects: A 7T fMRI Study.","authors":"Thomas Liebe, Lena Vera Danyeli, Zümrüt Duygu Sen, Meng Li, Jörn Kaufmann, Martin Walter","doi":"10.1093/ijnp/pyae022","DOIUrl":"10.1093/ijnp/pyae022","url":null,"abstract":"<p><strong>Background: </strong>The NMDA antagonist S-ketamine is gaining increasing use as a rapid-acting antidepressant, although its exact mechanisms of action are still unknown. In this study, we investigated ketamine in respect to its properties toward central noradrenergic mechanisms and how they influence alertness behavior.</p><p><strong>Methods: </strong>We investigated the influence of S-ketamine on the locus coeruleus (LC) brain network in a placebo-controlled, cross-over, 7T functional, pharmacological MRI study in 35 healthy male participants (25.1 ± 4.2 years) in conjunction with the attention network task to measure LC-related alertness behavioral changes.</p><p><strong>Results: </strong>We could show that acute disruption of the LC alertness network to the thalamus by ketamine is related to a behavioral alertness reduction.</p><p><strong>Conclusion: </strong>The results shed new light on the neural correlates of ketamine beyond the glutamatergic system and underpin a new concept of how it may unfold its antidepressant effects.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248058","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":"Ketamine, Dissociation, and Depression: What Is \"Special\" About Ketamine? (Revisited).","authors":"Mina M Rizk, James W Murrough","doi":"10.1093/ijnp/pyae024","DOIUrl":"10.1093/ijnp/pyae024","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305917","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":"Effects of Catecholaminergic and Transcranial Direct Current Stimulation on Response Inhibition.","authors":"Anna Helin Koyun, Paul Wendiggensen, Veit Roessner, Christian Beste, Ann-Kathrin Stock","doi":"10.1093/ijnp/pyae023","DOIUrl":"10.1093/ijnp/pyae023","url":null,"abstract":"<p><strong>Background: </strong>The principle of gain control determines the efficiency of neuronal processing and can be enhanced with pharmacological or brain stimulation methods. It is a key factor for cognitive control, but the degree of how much gain control may be enhanced underlies a physical limit.</p><p><strong>Methods: </strong>To investigate whether methylphenidate (MPH) and transcranial direct current stimulation (tDCS) share common underlying mechanisms and cognitive effects, we administered MPH and anodal tDCS (atDCS) over the right inferior frontal gyrus both separately and combined, while healthy adult participants (n = 104) performed a response selection and inhibition task. The recorded EEG data were analyzed with a focus on theta band activity, and source estimation analyses were conducted.</p><p><strong>Results: </strong>The behavioral data show that MPH and atDCS revealed interactive effects on the ability to inhibit responses. Both MPH and atDCS modulated task-related theta oscillations in the supplementary motor area when applied separately, making a common underlying mechanism likely. When both stimulation methods were combined, there was no doubling of effects in the supplementary motor area but a shift to inferior frontal areas in the cortical network responsible for theta-driven processing.</p><p><strong>Conclusions: </strong>The results indicate that both MPH and atDCS likely share a common underlying neuronal mechanism, and interestingly, they demonstrate interactive effects when combined, which are most likely due to the physical limitations of gain control increases. The current study provides critical groundwork for future combined applications of MPH and non-invasive brain stimulation.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11184454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916606","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":"Characterization of the Neurochemical and Behavioral Effects of the Phenethylamine 2-Cl-4,5-MDMA in Adolescent and Adult Male Rats.","authors":"Gessica Piras, Cristina Cadoni, Francesca Caria, Nicholas Pintori, Enrica Spano, Maksims Vanejevs, Anastasija Ture, Graziella Tocco, Nicola Simola, Maria Antonietta De Luca","doi":"10.1093/ijnp/pyae016","DOIUrl":"10.1093/ijnp/pyae016","url":null,"abstract":"<p><strong>Background: </strong>The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted.</p><p><strong>Methods: </strong>By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine (DA) and serotonin (5-HT) neurotransmission in two brain areas critical for the motivational and rewarding properties of drugs, the nucleus accumbens (NAc) shell and the medial prefrontal cortex (mPFC). Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA and the emission of 50-kHz ultrasonic vocalizations (USVs) to characterize its affective properties.</p><p><strong>Results: </strong>2-Cl-4,5-MDMA increased dialysate DA and 5-HT in a dose-, brain area-, and age-dependent manner. Notably, 2-Cl-4,5-MDMA more markedly increased dialysate DA in the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on dialysate 5-HT in the NAc shell, with adolescent rats being more responsive. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. Finally, 2-Cl-4,5-MDMA did not stimulate the emission of 50-kHz USVs.</p><p><strong>Conclusions: </strong>This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA by increasing awareness on possible health damage in users.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11120233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305543","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":"Altered serotonin 1B receptor binding after escitalopram for depression is correlated with treatment effect","authors":"M Gärde, G J Matheson, K Varnäs, P Svenningsson, E Hedman-Lagerlöf, J Lundberg, L Farde, M Tiger","doi":"10.1093/ijnp/pyae021","DOIUrl":"https://doi.org/10.1093/ijnp/pyae021","url":null,"abstract":"Background Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT) but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI-administration in primates and rodents respectively. The effect of SSRI treatment on 5-HT1B receptor binding in MDD subjects has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. Methods Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3-4 weeks of treatment with the SSRI escitalopram 10mg daily. Depression severity was assessed at time of PET and after 6-7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale (MADRS). Results We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (p = 0.036). Change in DBS [11C]AZ10419369 binding correlated with MADRS reduction after three (r = 0.78, p = 0.021) and seven (r = 0.94, p &amp;lt; 0.001) weeks’ treatment. Conclusions Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"17 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140826847","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":"Understanding the therapeutic action of antipsychotics: from molecular to cellular targets with focus on the islands of Calleja","authors":"Merve Direktor, Peter Gass, Dragos Inta","doi":"10.1093/ijnp/pyae018","DOIUrl":"https://doi.org/10.1093/ijnp/pyae018","url":null,"abstract":"The understanding of the pathophysiology of schizophrenia as well as the mechanisms of action of antipsychotic drugs remains a challenge for psychiatry. The demonstration of the therapeutic efficacy of several new atypical drugs targeting multiple different receptors apart from the classical dopamine D2 receptor as initially postulated unique antipsychotic target, complicated even more conceptualization efforts. Here we discuss results suggesting a main role of the islands of Calleja, still poorly studied GABAergic granule cell clusters in the ventral striatum, as cellular targets of several innovative atypical antipsychotics (clozapine, cariprazine and xanomeline/emraclidine) effective in treating also negative symptoms of schizophrenia. We will emphasize the potential role of dopamine D3 and M4 muscarinic acetylcholine receptor expressed at highest level by the islands of Calleja, as well as their involvement in schizophrenia-associated neurocircuitries. Finally, we will discuss the implications of new data showing ongoing adult neurogenesis of the islands of Calleja, as a very promising antipsychotic target linking long-life neurodevelopment and dopaminergic dysfunction in the striatum.","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"81 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609015","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}