Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Neural circuits mediating chronic stress: Implications for major depressive disorder","authors":"Hongling Guo ,&nbsp;Tahir Ali ,&nbsp;Shupeng Li","doi":"10.1016/j.pnpbp.2025.111280","DOIUrl":"10.1016/j.pnpbp.2025.111280","url":null,"abstract":"<div><div>Major depressive disorder (MDD), also known as depression, is a prevalent mental disorder that leads to severe disease burden worldwide. Over the past two decades, significant progress has been made in understanding the pathogenesis and developing novel treatments for MDD. Among the complicated etiologies of MDD, chronic stress is a major risk factor. Exploring the underlying brain circuit mechanisms of chronic stress regulation has been an area of active research for recent years. A growing body of preclinical and clinical research has revealed that abnormalities in the brain circuits are closely associated with failures in coping with stress in depressed individuals. Nevertheless, neural circuit mechanisms underlying chronic stress processing and the onset of depression remain a major puzzle. Here, we review recent literature focusing on circuit- and cell-type-specific dissection of depression-like behaviors in chronic stress-related animal models of MDD and outline the key questions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111280"},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143200846","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":"Alcohol outcomes on anxiety, impulsivity and spatial memory: Possible Omega-3 amelioration effects","authors":"Valentín Cabrera ,&nbsp;Paula Abate ,&nbsp;Verónica Balaszczuk ,&nbsp;Ana Fabiola Macchione","doi":"10.1016/j.pnpbp.2025.111281","DOIUrl":"10.1016/j.pnpbp.2025.111281","url":null,"abstract":"<div><div>Alcohol consumption is a worldwide concern that causes 5 % of the global disease burden and contributes to 3 million deaths per year. Several studies suggest an increase in alcohol drinking and alcohol related problems. Alcohol Use Disorder (formerly referred as alcoholism or alcohol addiction) is one of many possible outcomes of an early and prolonged alcohol consumption and it is highly comorbid with anxiety disorders, impulsivity and memory deficits among others. In this review we approach recent data about global and American prevalence of alcohol use and discuss different factors that contribute to alcohol consumption. Furthermore, we revise evidence of ethanol effects on anxiety-like behaviors, impulsivity and spatial memory. Lastly, we look at the Omega-3 fatty acid as a possible course of action in mitigating the aforementioned deleterious effects of alcohol consumption.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111281"},"PeriodicalIF":5.3,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191446","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":"Psychedelics in neuroinflammation: Mechanisms and therapeutic potential","authors":"Junia Lara de Deus ,&nbsp;Juliana Marino Maia ,&nbsp;Renato Nery Soriano ,&nbsp;Mateus R. Amorim ,&nbsp;Luiz G.S. Branco","doi":"10.1016/j.pnpbp.2025.111278","DOIUrl":"10.1016/j.pnpbp.2025.111278","url":null,"abstract":"<div><div>Neuroinflammation is a critical factor in the pathogenesis of various neurodegenerative and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder. Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), have demonstrated promising therapeutic effects on neuroinflammation, primarily through interactions with serotonin (5-HT) receptors, particularly the 5-HT2A receptor. Activation of these receptors by psychedelics modulates the production of pro-inflammatory cytokines, regulates microglial activity, and shifts the balance between neurotoxic and neuroprotective metabolites. Additionally, psychedelics affect critical signaling pathways, including the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and mechanistic target of rapamycin (mTOR) pathways, promoting neuroplasticity and exerting anti-inflammatory effects. Beyond the serotonergic system, other neurotransmitter systems—including the glutamatergic, dopaminergic, noradrenergic, gamma-aminobutyric acid (GABAergic), and cholinergic systems—also play significant roles in mediating the effects of psychedelics. This review examines the intricate mechanisms by which psychedelics modulate neuroinflammation and underscores their potential as innovative therapeutic agents for treating neuroinflammatory and neuropsychiatric disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111278"},"PeriodicalIF":5.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076381","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":"Causal relationship between mental disorders and abdominal aortic aneurysm: Insights from the genetic perspective","authors":"Ming-Gang Deng ,&nbsp;Chen Chai ,&nbsp;Kai Wang ,&nbsp;Zhi-Hui Zhao ,&nbsp;Jia-Qi Nie ,&nbsp;Fang Liu ,&nbsp;Yuehui Liang ,&nbsp;Jiewei Liu","doi":"10.1016/j.pnpbp.2025.111277","DOIUrl":"10.1016/j.pnpbp.2025.111277","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to investigate the genetic link between mental disorders—depression, schizophrenia (SCZ), and bipolar disorder (BIP)—and abdominal aortic aneurysm (AAA).</div></div><div><h3>Methods</h3><div>We first examined the genetic associations between AAA and mental disorders by analyzing global and local genetic correlations as well as shared genomic loci. Global genetic correlation was assessed using linkage disequilibrium score regression (LDSC) and the GeNetic cOVariance Analyzer (GNOVA), while local genetic correlation was analyzed using the SUPERGNOVA approach. To identify shared genetic variants, the pleiotropy-informed conditional and conjunctional false discovery rate (pleioFDR) method was applied. Subsequently, the univariate Mendelian Randomization (UMR) was employed to evaluate the causal relationship, complemented by multivariate MR (MVMR) to account for potential confounding biases. Additionally, mediation analysis was performed to determine whether known risk factors mediate the identified causal relationships.</div></div><div><h3>Results</h3><div>Global correlations showed positive links between depression, SCZ, and AAA, but not BIP. Local analyses identified specific genomic regions of correlation. We found 26, 141, and 10 shared loci for AAA with depression, SCZ, and BIP, respectively. UMR indicated significant associations between genetically predicted depression (OR 1.270; 95 % CI 1.071–1.504; <em>p</em> = 0.006) and SCZ (OR 1.047; 95 % CI 1.010–1.084; <em>p</em> = 0.011) with AAA, but not BIP. These results were confirmed by MVMR analyses. Mediation analyses showed that smoking, hypertension, hyperlipidemia, and coronary atherosclerosis mediated the impact of depression on AAA while smoking mediated SCZ's impact.</div></div><div><h3>Conclusion</h3><div>This study provides evidence that genetically predicted depression and SCZ are linked to an increased risk of AAA, mediated by traditional AAA risk factors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111277"},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076371","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":"Effective non-invasive brain stimulation over dorsolateral prefrontal cortex for modulation of food craving and consumption: A systematic and meta-analytic review","authors":"Lei Zheng ,&nbsp;Yinqiang Yu ,&nbsp;Xuebing Wu ,&nbsp;Jun Hu ,&nbsp;Yiqun Gan","doi":"10.1016/j.pnpbp.2025.111271","DOIUrl":"10.1016/j.pnpbp.2025.111271","url":null,"abstract":"<div><div>In recent decades, non-invasive brain stimulation (NIBS) has gained attention as a potential tool for promoting dietary regulation by modulating activity in the dorsolateral prefrontal cortex (dlPFC). However, the findings from individual experimental studies and meta-analyses have been inconsistent. To address this, we conducted a meta-analytic and systematic review of past studies focusing on neuromodulation of the dlPFC. Our research included 13 studies using repetitive transcranial magnetic stimulation (rTMS; 16 samples, 506 participants) and 29 transcranial direct current stimulation (tDCS; 31 samples, 1004 participants). By adjusting the pre-post correlation, we detected small-to-moderate effect sizes of NIBS on food craving (rTMS: Hedge's g = −0.57; tDCS: Hedge's g = −0.26) and food consumption (rTMS: Hedge's g = −0.51; tDCS: Hedge's g = −0.17). Additionally, we observed that the efficacy of NIBS was influenced by various moderators, including stimulation parameters, research protocols, and participant characteristics. Notably, both rTMS and tDCS appeared to enhance dlPFC function in dietary regulation for people with eating disorders or obesity. Furthermore, these effects were more pronounced with multi-session stimulation compared to single-session stimulation. Finally, based on the existing literature, we discuss the role of the dlPFC in the appetitive reward processing pathway and provide suggestions for future research directions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111271"},"PeriodicalIF":5.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076375","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":"Executive dysfunction in Parkinson's disease: From neurochemistry to circuits, genetics and neuroimaging","authors":"Shuyan Tong ,&nbsp;Ruiwen Wang ,&nbsp;Huihua Li ,&nbsp;Zhu Tong ,&nbsp;Deqin Geng ,&nbsp;Xiangrong Zhang ,&nbsp;Chao Ren","doi":"10.1016/j.pnpbp.2025.111272","DOIUrl":"10.1016/j.pnpbp.2025.111272","url":null,"abstract":"<div><div>Cognitive decline is one of the most significant non-motor symptoms of Parkinson's disease (PD), with executive dysfunction (EDF) being the most prominent characteristic of PD-associated cognitive deficits. Currently, lack of uniformity in the conceptualization and assessment scales for executive functions impedes the early and accurate diagnosis of EDF in PD. The neurobiological mechanisms of EDF in PD remain poorly understood. Moreover, the treatment of cognitive impairment in PD has progressed slowly and with limited efficacy. Thus, this review explores the characteristics and potential mechanisms of EDF in PD from multiple perspectives, including the concept of executive function, commonly used neuropsychological tests, neurobiochemistry, genetics, electroencephalographic activity and neuroimaging. The available evidence indicates that degeneration of the frontal-striatal circuit, along with mutations in the Catechol-<em>O</em>-methyltransferase (COMT) gene and Leucine-rich repeat kinase 2 (LRRK2) gene, may contribute to EDF in patients with PD. The increase in theta and delta waves, along with the decrease in alpha waves, offers potential biomarkers for the early identification and monitoring of EDF, as well as the development of dementia in patients with PD. The PD cognition-related pattern (PDCP) pattern may serve as a tool for monitoring and assessing cognitive function progression in these patients and is anticipated to become a biomarker for cognitive disorders associated with PD. The aim is to provide new insights for the early and precise diagnosis and treatment of EDF in PD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111272"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069531","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":"Dysbiosis is associated with the behavioral phenotype observed in the triple-hit Wisket rat model of schizophrenia","authors":"Szonja B. Plesz ,&nbsp;Leatitia G. Adlan ,&nbsp;Alexandra Büki ,&nbsp;Nóra Makra ,&nbsp;Balázs Ligeti ,&nbsp;Bence Ágg ,&nbsp;Dóra Szabó ,&nbsp;Zoltán S. Zádori ,&nbsp;Péter Ferdinandy ,&nbsp;Gyongyi Horvath ,&nbsp;Gabriella Kekesi","doi":"10.1016/j.pnpbp.2025.111276","DOIUrl":"10.1016/j.pnpbp.2025.111276","url":null,"abstract":"<div><div>Comorbidities between gastrointestinal diseases and psychiatric disorders have been widely reported, with the gut–brain axis implicated as a potential biological basis. Thus, dysbiosis may play an important role in the etiology of schizophrenia, which is barely detected. Triple-hit Wisket model rats exhibit various schizophrenia-like behavioral phenotypes. The present study aimed to compare the diversity and abundance of gut microbiota in Wisket model and control rats; furthermore, to correlate the microbial taxonomic profiles to indices of behavioral change.</div><div>Tail-flick and Ambitus tests were used to assess acute heat pain sensitivity, and record exploration and locomotor activity along with motivation in young adult, control and Wisket model rats. Fecal microbiota composition was profiled by deep sequencing of bacterial 16S rRNA, and it was correlated to behavioral phenotype.</div><div>Wisket rats exhibited significantly decreased pain sensitivity, lower locomotor activity and exploration, and impaired motivation compared with controls. No significant differences were observed in bacterial alpha diversity between the groups; however, clear differences in community structure were observed. Wisket rats showed decreases in several genera of <em>Firmicutes</em> and <em>Saccharimonas</em>, and increases in <em>Bacteriodetes</em> and <em>Helicobacter</em> phyla compared with controls. Correlation analysis revealed significant associations between the microbiota profile and the behavioral phenotype.</div><div>This is the first demonstration that fecal microbiota composition is markedly altered in a triple-hit schizophrenia rat model, suggesting the contribution of the microbiota–gut–brain axis in the development of the schizophrenia-like behavioral phenotype. Thus targeting the gut microbiota may be a novel approach to treat such impairments.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111276"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069537","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":"What are the levels and interactions of neuroligin-1, neuroligin-3, and inflammatory cytokines (IL-6, IL-8) in children diagnosed with autism spectrum disorder?","authors":"Kübra Kılınç ,&nbsp;Serhat Türkoğlu ,&nbsp;Ramazan Kocabaş ,&nbsp;Hasan Ali Güler ,&nbsp;Çiğdem Yılmaz ,&nbsp;Ayşe Büyükateş","doi":"10.1016/j.pnpbp.2025.111275","DOIUrl":"10.1016/j.pnpbp.2025.111275","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is characterized by deficits in social interaction, restricted interests, and repetitive behaviors. Several genes, including synaptic proteins and environmental risk factors, play a role in the etiology of autism. We aimed to evaluate the relationship between neuroligin-1 (NLGN-1) and neuroligin-3 (NLGN-3) levels, which are neuronal cell adhesion molecules (CAMs), and inflammatory cytokine (IL-6, IL-8) levels with disease severity and symptom clusters and with each other in children with ASD. Eighty children diagnosed with autism who met the inclusion criteria and sixty-five typically developing children matched for age and sex were included in the study. The children were evaluated psychiatrically through a semi-structured interview, DSM-5 criteria, the Childhood Autism Rating Scale (CARS), and the Social Communication Questionnaire (SCQ). IL-6, IL-8, NLGN-1, and NLGN-3 levels were analyzed in peripheral serum samples using human ELISA kits. IL-8 and NLGN-3 levels were higher in the autism group (<em>p</em> &lt; 0.001, p &lt; 0.001). IL-6 was positively related to CARS and SCQ total scores (<em>p</em> = 0.021, <em>p</em> = 0.040, respectively). IL-8, and NLGN-3 were positively associated with the all subtests of the SCQ and the SCQ total score (all <em>p</em> values &lt;0.001). NLGN-1, NLGN-3, and inflammatory cytokine (IL-6, IL-8) levels were positively correlated (all p values &lt;0.001). Neuroligins play a central role in the brain's ability to process information and maybe a key target in the pathogenesis of ASD. Further research is needed to determine whether, to what extent and how neuronal CAMs and immunity modulate each other and whether this contributes to ASD pathogenesis. Future studies should also be expanded to investigate the influence of variables such as oxidative stress, metalloproteases responsible for ectodomain shedding, or epigenetic regulation.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111275"},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061501","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":"Attention-deficit/hyperactivity disorder-related psychomotor activity and altered neuronal activity in the medial prefrontal cortex and striatum in the A53T mouse model of Parkinson's disease and other synucleinopathies: Findings from an “endophenotype” approach","authors":"Olga Dubljević ,&nbsp;Željko Pavković ,&nbsp;Maja Srbovan ,&nbsp;Milica Potrebić ,&nbsp;Miloš Stanojlović ,&nbsp;Vesna Pešić","doi":"10.1016/j.pnpbp.2025.111273","DOIUrl":"10.1016/j.pnpbp.2025.111273","url":null,"abstract":"<div><div>Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with an increased risk of Parkinson's disease (PD) and other synucleinopathies later in life. The severity of the ADHD phenotype may play a significant role in this association. There is no indication that any of the existing animal models can unify these disorders. Using the Open Field Test, amphetamine-challenge test, Western blot and immunohistochemical analysis of neuronal activity markers (c-Fos, FosB and ΔFosB) we performed a deliberate neurobehavioral characterization of 6-month-old hemizygous A53T carriers (A53T+) of the JAX006823 strain, evaluating the utility of this transgenic mouse model of PD and other synucleinopathies in ADHD/PD continuum research. Adhering to the “endophenotype” approach, non-transgenic littermates (A53T-) and C57BL/6J mice (used to maintain the colony) were examined with A53T+ mice, to differentiate between biomarkers of transgenicity and endophenotypic traits related to the genetic background of the strain. Obtained results revealed that increased behavioral and acute striatal response to novelty, increased basal neuronal activity of the ventromedial prefrontal cortex and rate-dependent calming effect of amphetamine were endophenotypic characteristics of the strain. Increased acute response of the medial prefrontal cortex to novelty and chronic increase in neuronal activity of the striatum appeared as the mark of transgenicity. To the best of our knowledge, this is the first study to indicate external validity of a transgenic mouse model of PD and other synucleinopathies with the neurobehavioral pathology associated with ADHD, hinting at its potential in preclinical research of ADHD/PD continuum. The full capacity of the model remains to be explored.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111273"},"PeriodicalIF":5.3,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054172","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":"Time-dependent fear memory generalization triggered by phosphodiesterase 5 inhibition during reconsolidation","authors":"Nathalie Carla Cardoso ,&nbsp;Jeferson Machado Batista Sohn ,&nbsp;Ana Maria Raymundi ,&nbsp;Mateus Reis Santos ,&nbsp;Jos Prickaerts ,&nbsp;Lucas Gazarini ,&nbsp;Cristina Aparecida Jark Stern","doi":"10.1016/j.pnpbp.2025.111274","DOIUrl":"10.1016/j.pnpbp.2025.111274","url":null,"abstract":"<div><div>Fear generalization, a lack of discrimination between safe and unsafe cues, is a hallmark of posttraumatic stress disorder. The phosphodiesterase 5 (PDE5) regulates the cyclic guanosine monophosphate (cGMP) pathway, which has been proposed to be involved in fear memory generalization. However, whether PDE5 activity underlies fear memory generalization remains unexplored. Considering the importance of retrieval-induced reconsolidation in memory maintenance, we aimed to investigate whether PDE5 inhibition during reconsolidation of recent fear memory affects generalization over time in adult male Wistar rats submitted to contextual fear conditioning. The PDE5 inhibition with vardenafil (VAR) 1 mg/kg i.p. during reconsolidation triggered a time-dependent fear generalization without affecting fear memory in the paired context. Fear generalization and impaired pattern separation appear to be interlinked. Likewise, an impairment of object pattern separation was observed in the VAR-treated group at the remote time point. These effects depended on memory retrieval and were restricted to the reconsolidation time window. A chemogenetic inhibition of the anterior cingulate cortex (ACC), a region involved in allocating remote memories and generalization, prevented the effects of VAR. Moreover, VAR infusion into the ACC (6 μg/0.2 μL) after retrieval also promoted fear generalization and impaired OPS in remote time point, suggesting that ACC underlies the behavioral outcomes of the treatment with VAR. In conclusion, our results suggest that inhibiting PDE5 during the reconsolidation of a recent fear memory recruits the activity of the ACC, triggering fear memory generalization and impairing object pattern separation over time.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111274"},"PeriodicalIF":5.3,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054185","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}