International Journal of Neuropsychopharmacology最新文献

{"title":"Illicit substance exposure in pregnancy and infant mortality risk: a nationwide Taiwan study.","authors":"Chun Lin, Mu-Hong Chen, Wei-Szu Lin, Shiow-Ing Wu, Yuan-Chun Liao, Yu-Hsuan Lin, Ching-Heng Lin","doi":"10.1093/ijnp/pyaf046","DOIUrl":"10.1093/ijnp/pyaf046","url":null,"abstract":"<p><strong>Background: </strong>To investigate the association between prenatal illicit substance exposure and infant mortality, addressing the unclear links between specific and multiple substances and increased mortality.</p><p><strong>Methods: </strong>This 16-year retrospective cohort study used Taiwan's National Health Insurance Research Database, the Taiwan Maternal and Child Health dataset, and the Integrated Illegal Drug Database, including 1 937 301 pregnant women who delivered from 2004 to 2019. Among them, 11 477 used illicit drugs during pregnancy, with a matched control group of 45 908 non-users based on maternal age, income, and childbirth year. Of the drug users, 26.9% used multiple substances, primarily methamphetamine and opioids. The primary outcome was all-cause mortality within the first year of life, with analyses stratified by substance type and timing of exposure. Cox regression models were employed to assess mortality, with results presented as adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). A P-value below .05 was considered statistically significant.</p><p><strong>Results: </strong>Infant from illicit drug-exposed mothers had a higher all-cause mortality rate (0.7%) compared to the control group (0.4%). Polysubstance use, which in most cases involved methamphetamine or opioids, was significantly associated with increased mortality risk (aHR 1.53, 95% CI 1.00-2.34), whereas no single substance alone-including methamphetamine (aHR 1.38, 95% CI 0.87-2.19) or opioids (aHR 1.63, 95% CI 0.98-2.72)-showed a statistically significant association. 3,4-Methylenedioxymethamphetamine, ketamine, and cannabis were likewise not linked to increased mortality. Mortality risk increased with drug exposure during pregnancy, with borderline significant associations in the first (aHR 1.82, 95% CI 0.98-3.37) and second trimesters (aHR 1.96, 95% CI 0.99-3.86), suggesting heightened vulnerability during early to mid-gestation.</p><p><strong>Conclusion: </strong>One-year infant mortality is elevated among women with illicit substance use, with a higher proportion of deaths attributed to preterm birth and hypoxic events. The highest mortality risk was observed among those with polysubstance use. The findings underscore a dire public health issue, associating prenatal illicit substance exposure, notably multiple substances use, opioids, and methamphetamine, with heightened infant mortality rates, calling for targeted interventions and further research.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591199","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":"Frequent vocalizations and deep brain stimulation-responsive hyperkinesia in a striatal disinhibition rat model for Tourette syndrome.","authors":"Boriss Sagalajev, Lina Lennartz, Niloofar Mokhtari, Mikolaj Szpak, Meryem Sinem Uyar, Thomas Schüller, Juan Carlos Baldermann, Pablo Andrade, Veerle Visser-Vandewalle, Thibaut Sesia","doi":"10.1093/ijnp/pyaf039","DOIUrl":"10.1093/ijnp/pyaf039","url":null,"abstract":"<p><strong>Background: </strong>The lack of a rodent model for both motor and phonic tics hinders research on deep brain stimulation (DBS) for refractory Tourette syndrome (TS). Striatal disinhibition with a gamma-aminobutyric acid A antagonist (bicuculline) was previously shown to induce hyperkinesia and vocalizations in monkeys, indicating its potential as a TS model. In rats, however, only hyperkinesia was validated, prompting us to investigate whether they can also develop abnormal vocalizations and whether both conditions respond to thalamic DBS.</p><p><strong>Methods: </strong>Rats underwent surgical implantation of a unilateral guide cannula targeting the caudate putamen (CPu) or nucleus accumbens (NAc). Additionally, they were implanted with an ipsilateral stimulation electrode targeting the border between the central medial (CM) and ventrolateral (VL) thalamic nuclei. Motor changes and ultrasound vocalizations were recorded and characterized offline.</p><p><strong>Results: </strong>CPu bicuculline elicited arrhythmic shoulder jerks that tend to appear in fading bursts and sporadically alternate with sustained generalized hyperextension. Nucleus accumbens bicuculline elicited similar hyperkinesia, but at a much lower dose to prevent convulsions. DBS of CM/VL, but not adjacent regions, attenuated hyperkinesia with lower intensity showing stronger effects. In addition, bicuculline in NAc, but not CPu, elicited nonsensical vocalizations. However, the effect of CM/VL DBS on vocalizations remained inconclusive.</p><p><strong>Conclusions: </strong>Hyperkinesia temporal features, co-development with vocalizations, and responsiveness to CM/VL DBS suggest striatal disinhibition may serve as a TS rat model. However, other movement disorders with vocal complications cannot be excluded, given the challenge of validating key tic indicators in animals, such as premonitory urge and suppressibility.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283862","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":"Correction to: From theory to therapy: unlocking the potential of muscarinic receptor activation in schizophrenia with the dual M1/M4 muscarinic receptor agonist xanomeline and trospium chloride and insights from clinical trials.","authors":"","doi":"10.1093/ijnp/pyaf051","DOIUrl":"10.1093/ijnp/pyaf051","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"28 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690163","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":"Predicting antidepressant responsiveness in major depressive disorder patients via electroencephalography gamma-band dynamic functional connectivity in response to salient auditory stimuli.","authors":"Kang-Min Choi, Taegyeong Lee, Seung-Hwan Lee, Chang-Hwan Im","doi":"10.1093/ijnp/pyaf042","DOIUrl":"10.1093/ijnp/pyaf042","url":null,"abstract":"<p><strong>Background: </strong>Heterogeneous pathophysiological characteristics in patients with major depressive disorder (MDD) lead to individually differentiated sensitivities to antidepressants. Based on the hypothesis that gamma-band dynamic fluctuations in cortical functional connectivity (FC) in response to salient stimuli are linked to pathophysiological characteristics, we conducted a classification analysis for antidepressant responsiveness prediction.</p><p><strong>Methods: </strong>Biosignals and psychological measures were acquired from 47 patients with MDD prior to treatment. After 8 weeks of antidepressant therapy, patients were divided into non-remitted MDD (nrMDD; aged 42.55 ± 11.52 years; n = 20) and remitted MDD (rMDD; aged 47.22 ± 11.59 years; n = 27) groups based on their depressive symptom reduction. Electroencephalography (EEG) signals were acquired during the duration-variant auditory mismatch negativity paradigm. From the deviant condition, gamma-band weighted phase-lag index-based dynamic fluctuations were evaluated using a template generated from 21 demography-matched healthy control (aged 43.81 ± 14.10 years) data.</p><p><strong>Results: </strong>Using these dynamic functional connectivity (dFC) features, a machine learning-based classification analysis was performed for nrMDD and rMDD. Using leave-one-out cross-validation, the linear discriminant analysis classifier achieved the best accuracy (82.98%) for classifying nrMDD and rMDD. Further simple effect analyses identified three core dFC features for nrMDD: (i) relatively intact time-dependent FC between the left frontal and right temporal regions; (ii) disrupted right frontoparietal FC; and (iii) disrupted left fronto-temporal FC. These dFC features commonly exhibit transient hyperconnections in patients with nrMDD.</p><p><strong>Conclusions: </strong>We demonstrated that gamma-band dFC responses to salient stimuli could serve as potential biomarkers for antidepressant responsiveness prediction in patients with MDD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511906","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 influence of synaptic density and anxiety on pain perception: evidence from a [11C]UCB-J positron emission tomography imaging study.","authors":"Karina Moisieienko, Ruth H Asch, Margaret T Davis, Robert H Pietrzak, Irina Esterlis","doi":"10.1093/ijnp/pyaf040","DOIUrl":"10.1093/ijnp/pyaf040","url":null,"abstract":"<p><strong>Background: </strong>Structural and functional brain alterations may be associated with pain and anxiety. We hypothesized that synaptic density (measured in vivo with [11C]UCB-J and positron emission tomography quantification of synaptic vesicle glycoprotein 2A, SV2A) alterations may play a role in higher pain sensitivity and that this relationship may be mediated by anxiety symptoms.</p><p><strong>Methods: </strong>Twenty-one mentally and medically healthy subjects (11 males, 10 females; age 45.1 ± 16.9 years) participated in imaging, acute pain (cold pressor test) and anxiety (State-Trait Anxiety Inventory) assessments. Synaptic vesicle glycoprotein 2A density was quantified as regional volumes of distribution (VT) using a 1-tissue compartment model with a plasma input function. Synaptic vesicle glycoprotein 2A density was assessed in 5 regions of interest that were previously shown to be associated with pain: dorsolateral prefrontal cortex (dlPFC), amygdala, anterior cingulate cortex (ACC), fusiform gyrus, and cerebellum.</p><p><strong>Results: </strong>State anxiety was positively correlated with pain sensitivity (r = 0.60, P = .004). Significant negative correlations were observed between pain sensitivity and SV2A density in the cerebellum (r = -0.67, P = .001), fusiform gyrus (r = -0.66, P = .001), dlPFC (r = -0.63, P = .002), and ACC (r = -0.58, P = .006). Mediation analysis revealed a significant indirect effect of cerebellar synaptic density on pain sensitivity through state anxiety symptoms (B = -0.77, 95% CI [-1.89, -0.04]), accounting for 33% of the total effect. For the fusiform gyrus, the direct effect on pain sensitivity remained significant after controlling for anxiety symptoms (B = -1.67, P = .020), while the indirect effect through anxiety symptoms was not significant (B = -0.43, 95% CI [-1.44, 0.37]).</p><p><strong>Conclusions: </strong>Results provide the first known in vivo evidence that lower synaptic (SV2A) density is associated with greater pain sensitivity, particularly in the fusiform gyrus and cerebellum. Mediation analyses revealed that state anxiety partially mediated the relationship between cerebellar synaptic density and pain sensitivity, while having an additive-but not mediating-effect on the relationship between fusiform synaptic density and pain sensitivity.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283861","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":"Correction to: Inflammation and Blood-Brain Barrier in Depression: Interaction of CLDN5 and IL6 Gene Variants in Stress-Induced Depression.","authors":"","doi":"10.1093/ijnp/pyaf054","DOIUrl":"10.1093/ijnp/pyaf054","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"28 7","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144707447","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":"Efficacy and Safety of the Muscarinic Receptor Agonist KarXT (Xanomeline-Trospium) in Schizophrenia: A Systematic Review, Meta-Analysis and Bayesian Sensitivity Analysis.","authors":"Nikhil Sharma, Mahalaqua Nazli Khatib, R Roopashree, Mandeep Kaur, Manish Srivastava, Amit Barwal, G V Siva Prasad, Pranchal Rajput, Vinamra Mittal, Muhammed Shabil, Amit Kumar, Ganesh Bushi, Rachana Mehta, Prakasini Satapathy, Sanjit Sah","doi":"10.1093/ijnp/pyaf045","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf045","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia significantly impacts global health, with existing treatments primarily focusing on positive symptoms and often causing considerable side effects. KarXT, a novel treatment combining xanomeline, a muscarinic M1/M4 receptor agonist, and trospium, targets a broader range of symptoms including negative and cognitive deficits, potentially with fewer side effects. This systematic review and meta-analysis evaluates the efficacy and safety of KarXT in treating schizophrenia, assessing symptom reduction and safety profiles compared to placebo.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and Web of Science up to November 10, 2024, for randomized controlled trials (RCTs) assessing the efficacy and safety of KarXT in schizophrenia. Data were pooled using a random-effects model, assessing outcomes like Positive and Negative Syndrome Scale (PANSS) scores and incidence of treatment-emergent adverse events (TEAEs). R software (Version 4.4.) was used for meta-analysis.</p><p><strong>Results: </strong>Three RCTs involving 674 participants were included. KarXT significantly reduced total PANSS scores of mean difference (MD) -9.707 (95% CI: -12.329 to -7.085), with notable improvements in both negative (MD = -1.623; 95% CI: -2.461 to -0.785) and positive symptom subscales (MD = -3.213; 95% CI: -4.033 to -2.393). The treatment was associated with a higher incidence of TEAEs, predominantly constipation (RR: 2.77; 95% CI: 1.72-4.45) and nausea (RR: 4.87; 95% CI: 2.73-8.68) compared to placebo. Bayesian meta-analysis confirmed the results.</p><p><strong>Conclusion: </strong>KarXT offers significant improvements in both negative and positive symptoms of schizophrenia with a manageable safety profile. Its potential as a transformative treatment for schizophrenia highlights the need for further research to confirm these findings and to fully understand its long-term efficacy and safety.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575424","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":"NMDA receptor involvement in dopaminergic modulation of neuroplasticity induced by paired associative stimulation.","authors":"Marie C Beaupain, Elham Ghanavati, Amba M Frese, Lorena Melo, Min-Fang Kuo, Michael A Nitsche","doi":"10.1093/ijnp/pyaf038","DOIUrl":"10.1093/ijnp/pyaf038","url":null,"abstract":"<p><strong>Background: </strong>Dopamine (DA) modulates long-term potentiation (LTP)-like neuroplasticity. While particularly D1 and D2 receptors are thought to influence neuroplasticity through glutamatergic N-methyl-D-aspartate (NMDA) receptor and gamma-aminobutyric acid (GABA) modulation, the exact mechanisms are not completely clarified.</p><p><strong>Objective: </strong>We aimed to explore the relevance of NMDA receptor activity for DAergic modulation of focal LTP-like plasticity induced by excitatory paired associative stimulation (ePAS).</p><p><strong>Methods: </strong>In a double-blinded, randomized, and placebo-controlled design, 17 healthy participants received DAergic agents (100 mg L-Dopa for general DAergic enhancement, 10 mg bromocriptine for selective D2 receptor activation, or placebo) with different doses of the partial NMDA receptor agonist D-cycloserine (CYC; 50, 100, 200 mg, or placebo) and underwent ePAS. Cortical excitability was monitored via motor-evoked potentials induced by TMS over the left motor cortex for up to 2 hours post-stimulation.</p><p><strong>Results: </strong>We did not find significant interactions between DAergic agents, CYC, and time across the entire sample, but significant group differences depending on sensitivity to ePAS. In high-sensitivity, but not low-sensitivity participants, ePAS induced LTP-like effects. CYC produced nonlinear, dose-dependent effects on plasticity in both groups. In the high-sensitivity group, LTP-like effects persisted under both DAergic agents, but were significantly reduced under bromocriptine. CYC had a nonlinear effect when combined with bromocriptine. In the low-sensitivity group, ePAS under DAergic agents did not induce LTP-like effects, and only additional intervention with medium-dose CYC restored facilitatory effects under L-Dopa.</p><p><strong>Conclusions: </strong>These findings suggest that optimal NMDA receptor activation is necessary for ePAS-induced neuroplasticity and that D2 receptor activity may reduce LTP-like effects by downregulating NMDA receptor function.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181809","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":"Role of endogenous serotonin in psychedelic-like effects of psilocybin in mice.","authors":"Ines Erkizia-Santamaría, Nerea Martínez-Álvarez, Leyre Salinas-Novoa, Jose Javier Meana, Jorge Emilio Ortega","doi":"10.1093/ijnp/pyaf035","DOIUrl":"10.1093/ijnp/pyaf035","url":null,"abstract":"<p><strong>Background: </strong>The psychedelic psilocybin has been posited as efficacious for the treatment of depression. However, the potential link between the intensity of acute psychedelic effects and long-term therapeutic outcomes remains undiscovered. Moreover, the impact of classical antidepressant drugs that modulate serotonergic activity on psilocybin's effects is a clinically relevant concern. The aim of the present study was to assess serotonergic mechanisms implicated in the regulation of the intensity of the psilocybin-induced acute effects.</p><p><strong>Methods: </strong>The head-twitch response (HTR), the most translational behavioral assay to characterize the psychedelic-like effect in rodents was performed. Moreover, the role of endogenous serotonin (5-HT) on psilocybin-induced HTR was studied by in vivo brain microdialysis technique.</p><p><strong>Results: </strong>Maximally effective psilocybin dose (1 mg/kg) induced progressively lower HTR in heterozygous and homozygous knockout mice for serotonin 2A receptor (5HT2AR), compared to wild type. Synaptic increase of 5-HT by citalopram dose-dependently attenuated psilocybin-induced HTR after both acute and chronic dosing regimens. Conversely, depletion of 5-HT by p-chlorophenylalanine potentiated psilocybin-evoked HTR. Serotonin 1A receptor (5HT1AR) agonist 8-OH-DPAT dose-dependently decreased psilocybin-induced HTR, demonstrating functional interaction between 5HT2AR and 5HT1AR for psychedelic effects.</p><p><strong>Conclusions: </strong>The present findings reveal an inverse correlation between cortical 5-HT levels and the acute psychedelic-like effects of psilocybin. Consequently, the enhancement of serotonergic activity induced by prior antidepressant treatment may underlie interindividual variability in the acute response to psychedelics. Investigating these mechanisms in relation to the sustained therapeutic outcomes of psilocybin could contribute to optimizing the efficacy of psychedelic-based therapies.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142490","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":"Activating group II metabotropic glutamate receptors in the basolateral amygdala inhibits increases in reward seeking triggered by discriminative stimuli in rats.","authors":"Mandy Rita LeCocq, Amélie Mainville-Berthiaume, Isabel Laplante, Anne-Noël Samaha","doi":"10.1093/ijnp/pyaf030","DOIUrl":"10.1093/ijnp/pyaf030","url":null,"abstract":"<p><strong>Background: </strong>Reward-associated cues guide reward-seeking behaviors. These cues include conditioned stimuli (CSs), which occur following seeking actions and predict reward delivery, and discriminative stimuli (DSs), which occur response-independently and signal that a seeking action will produce reward. Metabotropic group II glutamate (mGlu2/3) receptors in the basolateral amygdala (BLA) modulate CS-guided reward seeking; however, their role in DS effects is unknown.</p><p><strong>Methods: </strong>We developed a procedure to assess DS and CS effects on reward seeking in the same subjects within the same test session. Female and male rats self-administered sucrose where DSs signaled periods of sucrose availability (DS+) and unavailability (DS-). During DS+ trials, lever presses produced sucrose paired with a CS+. During DS- trials, lever presses produced a CS- and no sucrose. Across 14 sessions, rats learned to load up on sucrose during DS+ trials and inhibit responding during DS- trials. We then determined the effects of intra-BLA microinfusions of the mGlu2/3 receptor agonist LY379268 on cue-evoked sucrose seeking during a test where the DSs and CSs were presented response-independently, without sucrose. Before testing, rats received intra-BLA microinjections of artificial cerebrospinal fluid (aCSF) or LY379268.</p><p><strong>Results: </strong>Under aCSF, only the DS+ and DS+CS+ combination triggered increases in reward-seeking behavior. The CS+ alone was ineffective. Intra-BLA LY379268 suppressed the increases in sucrose seeking triggered by the DS+ and DS+CS+ combination.</p><p><strong>Conclusions: </strong>Using a new procedure to test reward seeking induced by DSs and CSs, we show that BLA mGlu2/3 receptor activity mediates the incentive motivational effects of reward-predictive DSs.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964627","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}