Neuropsychopharmacology最新文献

{"title":"Comparing apples and oranges in TRD treatment: the importance of assumptions in network meta-analysis","authors":"Nora Runia, Gosse J. J. Mol, Isidoor O. Bergfeld, Guido A. van Wingen, Roel J. T. Mocking","doi":"10.1038/s41386-026-02392-4","DOIUrl":"10.1038/s41386-026-02392-4","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"1135-1136"},"PeriodicalIF":6.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to mol: Comparing apples and oranges in TRD treatment: the importance of assumptions in network meta-analysis","authors":"Johan Saelens, Anna Gramser, Victoria Watzal, Carlos A. Zarate Jr., Rupert Lanzenberger, Christoph Kraus","doi":"10.1038/s41386-026-02393-3","DOIUrl":"10.1038/s41386-026-02393-3","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"1137-1138"},"PeriodicalIF":6.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking the “olfactory” tubercle: a hedonic hotspot within ventral striatum","authors":"Yosuke Arima, Satoshi Ikemoto","doi":"10.1038/s41386-026-02389-z","DOIUrl":"10.1038/s41386-026-02389-z","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"982-983"},"PeriodicalIF":6.6,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic dysfunction and adaptation after NMDA receptor ablation in the mouse medial prefrontal cortex","authors":"Rachel M. Dick, Lydia B. Cunitz, Aurora Torres Pérez, Habsa Ahmed, Anisha P. Adke, Cristina Rivera Quiles, Jason S. Mitchell, Ezequiel Marron Fernandez de Velasco, Nicola M. Grissom, Patrick E. Rothwell","doi":"10.1038/s41386-026-02381-7","DOIUrl":"10.1038/s41386-026-02381-7","url":null,"abstract":"N-methyl-D-aspartate receptors (NMDARs) in the prefrontal cortex (PFC) are critical regulators of neuronal excitability, synaptic plasticity, and cognitive function. NMDAR disruptions, including pharmacological blockade and anti-NMDAR encephalitis, can mimic symptoms of schizophrenia. These observations support the glutamate hypothesis of schizophrenia, which posits that symptoms arise from abnormal corticolimbic glutamatergic signaling. Further evidence for this theory includes abnormal expression of NMDARs and decreased dendritic spine density in the PFC of individuals with schizophrenia, as well as altered spine density and synaptic transmission caused by genetic manipulation of NMDARs. However, it is unknown how progressive loss of NMDAR function in the PFC during adolescence—a developmental time period associated with symptom onset in schizophrenia —affects excitatory synaptic structure and function. In this study, we used in vivo genome editing to ablate expression of the Grin1 gene, which encodes the obligate GluN1 subunit of NMDARs, in medial PFC neurons of female and male adolescent mice. We assessed synaptic density and function in layer V pyramidal neurons using whole-cell patch-clamp electrophysiology, integrated with confocal imaging of dendritic spine architecture in recorded neurons. NMDAR ablation caused an early decrease in basilar dendritic spine density, followed by a rebound in spine density and a corresponding increase in AMPAR-mediated synaptic transmission. These effects of pan-neuronal NMDAR ablation were not observed after a more specific manipulation of excitatory neurons. Our findings demonstrate that NMDAR ablation triggers a cascading reorganization of local PFC networks, which may include compensatory processes that maintain allostasis but are impaired in disease states.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"1100-1109"},"PeriodicalIF":6.6,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02381-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continued progress and innovation at Neuropsychopharmacology (NPP)","authors":"Tony P. George, Lisa M. Monteggia","doi":"10.1038/s41386-026-02382-6","DOIUrl":"10.1038/s41386-026-02382-6","url":null,"abstract":"","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"981-981"},"PeriodicalIF":6.6,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02382-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147380505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hedonic hotspot in rat olfactory tubercle: map for mu-opioid, orexin, and muscimol enhancement of sucrose ‘liking’","authors":"Koshi Murata, Kent C. Berridge","doi":"10.1038/s41386-026-02374-6","DOIUrl":"10.1038/s41386-026-02374-6","url":null,"abstract":"Pleasure plays a crucial role in positive reinforcement and motivation. Brain regions able to amplify positive hedonic reactions to sweetness, known as ‘hedonic hotspots’, are distributed within the mesocorticolimbic reward systems. The olfactory tubercle (OT), a part of the ventral striatum that receives olfactory input, contains distinct functional domains: the anteromedial domain mediates approach motivation toward odors associated with food, whereas the lateral domain mediates avoidance motivation away from odors associated with danger. However, it has remained unclear whether the OT modulates hedonic reactions to pleasant sensations. In this study, we made pharmacological microinjections in OT of rats to examine whether these OT subregions can modulate hedonic reactions, as assessed by the taste reactivity test. Sweet oral infusions of sucrose solution were delivered into the mouth via an intraoral cannula, and the rats’ orofacial and somatic hedonic reactions were recorded and analyzed. We compared three pharmacological agents: mu-opioid receptor agonist DAMGO, orexin-A peptide, and GABAA receptor agonist muscimol. Microinjection of any of these drugs into the anteromedial OT subregion enhanced hedonic ‘liking’ reactions to sucrose. Furthermore, DAMGO injection into the anteromedial OT subregion recruited distant Fos expression in other ‘hedonic hotspots’, including in the caudal ventral pallidum and the rostromedial orbitofrontal cortex. By contrast, the same microinjections into the anterolateral OT subregion failed to enhance ‘liking’ reactions and, DAMGO oppositely increased aversive ‘disgust’ reactions. These findings suggest that the anteromedial OT contains a ‘hedonic hotspot’, whereas the anterolateral OT may contain a suppressive opioid ‘hedonic coldspot’. Thus, OT subregions may help causally modulate hedonic reactions to sweetness and flavor perception.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"984-996"},"PeriodicalIF":6.6,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing affective bias modification by first- and second-generation antidepressants in male rats using a translational behavioural task","authors":"Katie A. Kamenish, Emma N. Cahill, Emma S. J. Robinson","doi":"10.1038/s41386-026-02376-4","DOIUrl":"10.1038/s41386-026-02376-4","url":null,"abstract":"Negative affective biases influence cognitive and emotional behaviours and have been observed in patients with major depressive disorder. The neuropsychological hypothesis of antidepressant efficacy suggests direct modulation of affective biases may contribute to efficacy. Studies have shown conventional antidepressants can positively bias emotional processing following acute administration in humans. This study employs a rat model developed to study affective biases based on associative learning and memory, and used this assay to compare selected first versus second generation antidepressants. Dose-response experiments using the tricyclic antidepressant, amitriptyline (0.3–3.0 mg/kg), monoamine oxidase inhibitor, moclobemide (3.0–10.0 mg/kg) and serotonin specific re-uptake inhibitor, sertraline (1.0–10.0 mg/kg) were performed. Specific protocols permitted quantification of affective biases associated with new learning or the acute and sustained modulation of past experiences. All treatments positively biased new learning but exhibited differences in terms of their ability to modulate negatively biased memories. Amitriptyline and sertraline attenuated negatively biases memories when administered 1 h or 24 h before testing. Moclobemide had no effects on past experiences. No treatments had effects in the control reward learning assay. Although generally considered to have similar efficacy and time course of effects, the pharmacological profiles of these antidepressants differ. Previous work has shown that variations in affective bias modification are linked to both the time course of clinical effects and their interaction with experience-dependent plasticity. Integrating understanding of these neuropsychological differences within clinical practice has the potential to improve clinical outcomes for patients.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"1056-1064"},"PeriodicalIF":6.6,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02376-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147314657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disinhibition of ventral tegmental area during initial punishment learning causes enduring punishment insensitivity","authors":"Shannen Y. S. Tan, Michelle H. Shen, Luke J. Keevers, Matthew Williams-Spooner, Gavan P. McNally, Simon Killcross, Philip Jean-Richard-dit-Bressel","doi":"10.1038/s41386-026-02368-4","DOIUrl":"10.1038/s41386-026-02368-4","url":null,"abstract":"Avoiding actions with negative consequences is fundamental to adaptive behavior. Traditional theories suggest GABAergic inhibition of midbrain dopamine neurons, including those within ventral tegmental area (VTADA), mediate suppression of actions that lead to aversive outcomes. However, the role of dopamine inhibition in punishment learning remains unclear. To examine this, we conducted fiber photometry, pharmacological, and chemogenetic experiments in rats to measure VTADA activity and GABA input across punishment learning, and test their causal contribution to behavior. VTADA activity and GABA input phasically increased to response-elicited outcomes, with VTADA activity being more strongly activated by rewards, while GABA input being more strongly activated by shock punishers during initial punishment. Pharmacologically blocking GABAA receptors in VTA or chemogenetically activating VTADA neurons during initial, but not later, punishment sessions produced enduring deficits in punishment avoidance. These findings suggest long-term avoidance depends upon a critical window of GABA-mediated VTADA inhibition during punishment learning.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"1045-1055"},"PeriodicalIF":6.6,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02368-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hair cortisol concentrations as a putative biomarker for suicidal behavior","authors":"Lindsay Taraban, Emily Hone, Meilin Jia-Richards, Mary Ann Kelly, Jenna M. Lindsay, Sarah Riston, Zak Hutchinson, Thomas D. Walko III, Eli Goodfriend, Brian C. Thoma, Dara Sakolsky, Kehui Chen, Antoine Douaihy, David A. Brent, Anna L. Marsland, David A. Lewis, Nadine M. Melhem","doi":"10.1038/s41386-026-02344-y","DOIUrl":"10.1038/s41386-026-02344-y","url":null,"abstract":"Suicide is the 2nd leading cause of death for young adults in the United States, and rates are particularly high among psychiatric patients in the year following psychiatric hospitalization. However, the prediction of suicidal behavior continues to be a challenge. We examined hair cortisol concentrations (HCC)—reflecting HPA axis activity over the preceding months—as an objective marker of risk for suicidal behavior across the full spectrum of suicidal behavior, including death by suicide. Participants were 238 young adults across the spectrum of suicide (i.e., suicide; suicide attempt; suicidal ideation; psychiatric comparison; 57% male) and 43 individuals who died by drug overdose (56% male). Data were collected via self-report, clinical interview, medical records review, and hair sampling (i.e., 3 cm segments). Multivariate regression models were used to examine the relationship between group and HCC, controlling for covariates. HCC was significantly lower in individuals who died by suicide compared to those with a suicide attempt [Difference in EMMs (SE) = −0.64 (0.20), p = 0.010, d = 0.73], suicidal ideation [Est. Diff (SE) = −0.89 (0.20), p < 0.0001, d = 1.02], and psychiatric comparison individuals [Est. Diff (SE) = −0.74 (0.26), p = 0.022, d = 0.85]. Lower HCC may serve as an objective marker that signals risk for death by suicide among high-risk adults, which have important clinical implications for the prediction and prevention of suicide. Future studies with larger sample sizes are needed to replicate these findings and to make assaying HCC accessible for its translation into clinical practice.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"1084-1090"},"PeriodicalIF":6.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-026-02344-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146134014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypocretin receptor 1 blockade early in abstinence prevents incubation of cocaine seeking and normalizes dopamine transmission","authors":"Philip J. Clark, Volodar M. Migovich, Sanjay Das, Wei Xu, Yanan Zhang, Sandhya Kortagere, Rodrigo A. España","doi":"10.1038/s41386-025-02315-9","DOIUrl":"10.1038/s41386-025-02315-9","url":null,"abstract":"Abstinence from cocaine use has been shown to elicit a progressive intensification or incubation of cocaine craving/seeking that is posited to increase the likelihood of relapse. While the mechanisms underlying incubation of cocaine seeking remain elusive, considerable evidence suggests that abstinence from cocaine promotes mesolimbic dopamine adaptations that contribute to exaggerated cocaine seeking. Consequently, preventing these dopamine adaptations may reduce incubation of cocaine seeking and thereby decrease the likelihood of relapse. In the present studies, we first examined the relationship between incubation of cocaine seeking and dopamine transmission in the nucleus accumbens following abstinence from intermittent access to cocaine. Given the extensive evidence that hypocretins/orexins regulate motivation for cocaine, we then examined to what extent an intraperitoneal injection of a hypocretin receptor 1 antagonist on the first day of abstinence would prevent incubation of cocaine seeking and dopamine adaptations later in abstinence. Results indicated that abstinence from intermittent access to cocaine engendered robust incubation of cocaine seeking in both female and male rats. We also observed aberrant dopamine transmission, but only in rats that displayed incubation of cocaine seeking. Further, we showed that a single injection of the hypocretin receptor 1 antagonist, RTIOX-276, on the first day of abstinence prevented incubation of cocaine seeking and aberrant dopamine transmission. These findings suggest that hypocretin receptor 1 antagonism may serve as a viable therapeutic for reducing cocaine craving/seeking early in abstinence, thus reducing the likelihood of relapse.","PeriodicalId":19143,"journal":{"name":"Neuropsychopharmacology","volume":"51 6","pages":"1123-1134"},"PeriodicalIF":6.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41386-025-02315-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}