Pharmacology Biochemistry and Behavior最新文献

{"title":"Population-dependent impacts of para-chlorophenylalanine, a tryptophan hydroxylase inhibitor, on homebase formation and thigmotaxis in adult zebrafish","authors":"Cássio M. Resmim ,&nbsp;João V. Borba ,&nbsp;Rossano M. Silva ,&nbsp;Hevelyn S. Moraes ,&nbsp;Camilla W. Pretzel ,&nbsp;Julia Canzian ,&nbsp;Barbara D. Fontana ,&nbsp;Maribel A. Rubin ,&nbsp;Eduardo P. Rico ,&nbsp;Matthew O. Parker ,&nbsp;Denis B. Rosemberg","doi":"10.1016/j.pbb.2025.174042","DOIUrl":"10.1016/j.pbb.2025.174042","url":null,"abstract":"<div><div>Alterations in monoamine levels, such as serotonin, play a role in the pathophysiology of affective disorders. Para-chlorophenylalanine (pCPA), a tryptophan hydroxylase inhibitor, impairs serotonin synthesis and increases anxiety-like behaviors in various species. Outbred zebrafish population, such as short fin (SF) and leopard (LEO), differ in serotonin expression, habituation patterns, and responses to novel environments. Locomotor and exploratory profiles are strongly influenced by homebase behavior, which can be assessed in the open field test (OFT). To further investigate a putative role of the serotoninergic system in homebase formation and exploratory behavior dynamics, we administered pCPA to two zebrafish populations (SF and LEO) with distinct anxiety profiles and homebase occupancy. Fish received intraperitoneal injections of pCPA (300 mg/kg) or vehicle for two consecutive days, followed by a 30-min OFT 24 h later. Both pCPA-treated populations showed increased locomotion and periphery occupancy was elevated during the habituation period (first 15 min of testing). Although pCPA did not alter homebase-related behaviors in LEO, the SF population exhibited a delayed homebase formation, likely due to disrupted exploratory-related mechanisms. Furthermore, Principal Component Analysis (PCA) and K-means clustering revealed that behaviors related to periphery occupancy and distance traveled accounted for approximately 80 % of the observed data variability. Collectively, our data show that pCPA impairs homebase formation, with stronger effects in SF fish and increases thigmotaxis. Overall, these results suggest that pCPA disrupts the organization of exploratory behavior, particularly the habituation processes, probably associated with anxiety-like phenotypes.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174042"},"PeriodicalIF":3.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Administration of paroxetine during pregnancy affects behavioral changes and hippocampal cell proliferation in male offspring in rats","authors":"Junko Horie ,&nbsp;Tomoya Kinjo ,&nbsp;Masanobu Ito ,&nbsp;Toshihito Suzuki","doi":"10.1016/j.pbb.2025.174041","DOIUrl":"10.1016/j.pbb.2025.174041","url":null,"abstract":"<div><h3>Background</h3><div>Although the use of antidepressants during pregnancy has increased over the last several decades, their safety has remained a topic of debate. Selective serotonin reuptake inhibitors (SSRIs) can cross the placenta and affect perinatal outcomes in infants exposed during pregnancy. Recent studies suggest new risks for not only for structural malformations, but also long-term behavioral, developmental, and emotional disorders in offspring.</div></div><div><h3>Aim</h3><div>We aimed to elucidate the effects by which in utero paroxetine exposure may affect the behavior and hippocampus of the offspring of paroxetine-treated rodent mothers.</div></div><div><h3>Methods</h3><div>Paroxetine was administered daily to pregnant female Wistar rats from embryonic day (ED) 12.5 to ED 21 with oral sondes. Paroxetine 1 mg/kg/day or paroxetine 2.5 mg/kg/day or saline was given to the control group. We evaluated spontaneous locomotor activity, spontaneous alternation behavior using the Y-maze test, and anxiety behavior using the elevated plus maze (EPM) in male offspring at postnatal day 30. Bromodeoxyuridine (BrdU)-positive cells in the hippocampus were counted using a fluorescence microscope.</div></div><div><h3>Results</h3><div>Locomotor activities significantly increased in the paroxetine 2.5 mg compared with the control group. The paroxetine 2.5 mg group spent less time in the closed arm than did the control and paroxetine 1 mg groups in the EPM. The number of BrdU-positive cells in the dentate gyrus was significantly increased in the paroxetine 2.5 mg compared with the control group.</div></div><div><h3>Conclusions</h3><div>These findings suggest that oral administration of paroxetine during pregnancy induces hyperactivity, decreases anxiety, and increases cell proliferation in the hippocampus of male offspring.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174041"},"PeriodicalIF":3.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced novelty-seeking after early adolescent exposure to vicarious social defeat predicts the vulnerability of female mice to cocaine reward","authors":"María Ángeles Martínez-Caballero ,&nbsp;Claudia Calpe-López ,&nbsp;María Pilar García-Pardo ,&nbsp;María Carmen Arenas ,&nbsp;Jose Enrique de la Rubia Ortí ,&nbsp;María Benlloch ,&nbsp;Carmen Manzanedo ,&nbsp;María Asunción Aguilar","doi":"10.1016/j.pbb.2025.174039","DOIUrl":"10.1016/j.pbb.2025.174039","url":null,"abstract":"<div><div>Stressful experiences can have a serious impact on adolescents, as the process of brain maturation, particularly of the prefrontal cortex, takes place during this developmental period. In animal models, male mice exposed to social defeat during early or late adolescence show increased vulnerability to cocaine reward, but this effect has only been studied in late adolescent female mice exposed to Vicarious Intermittent Social Defeat (VISD). The aim of the present study was to investigate the biochemical and behavioural effects of exposure to VISD during early adolescence in female mice. VISD only induced anxiety-like symptoms in the elevated plus maze (EPM) and increased novelty-seeking behaviour in the hole-board test. Furthermore, the behavioural profile of VISD-exposed mice in these tests was associated with their vulnerability or resilience to cocaine reward in adulthood. Female mice that exhibited a higher frequency of entries in the closed arms of the EPM and a lower latency of dips in the hole-board subsequently acquired cocaine-induced conditioned place preference. Thus, exposure of female mice to VISD during early adolescence also induced short-term changes that increased sensitivity to cocaine reward in susceptible individuals.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174039"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological and genetic manipulation of glyoxalase-1 (GLO1) does not alter locomotor responses or conditioned place preference induced by cocaine or oxycodone.","authors":"Elizabeth Alcantara ,&nbsp;Michelle R. Doyle ,&nbsp;Clara A. Ortez ,&nbsp;Anne Ilustrisimo ,&nbsp;Bloom Stromberg ,&nbsp;Amanda M. Barkley-Levenson ,&nbsp;Abraham A. Palmer","doi":"10.1016/j.pbb.2025.174040","DOIUrl":"10.1016/j.pbb.2025.174040","url":null,"abstract":"<div><div>Methylglyoxal (MG) is an endogenously produced non-enzymatic side product of glycolysis that acts as a partial agonist at GABA_A receptors. MG is metabolized by the enzyme glyoxalase-1 (GLO1). Inhibition of GLO1 increases methylglyoxal levels, and has been shown to modulate various behaviors, including decreasing seeking of cocaine-paired cues and ethanol consumption. The goal of these studies was to determine whether manipulation of GLO1 could alter cocaine- or oxycodone-induced locomotor activation and/or conditioned place preference (CPP) to cocaine or oxycodone. We used both pharmacological and genetic manipulations of GLO1 to address this question. Administration of the GLO1 inhibitor s-bromobenzylglutathione cyclopentyl diester (pBBG) did not alter the locomotor response to cocaine or oxycodone. Additionally, pBBG had no significant effect on place preference for cocaine or oxycodone. Genetic knockdown of <em>Glo1</em>, which is conceptually similar to pharmacological inhibition, did not have any significant effects on CPP to cocaine. Finally, <em>Glo1</em> overexpression did not affect locomotor response to cocaine. In summary, our results did not show any effect of pharmacological or genetic manipulations of GLO1 on the locomotor response or CPP to either cocaine or oxycodone.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174040"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-dependent changes induced by combined low-level systemic inflammation and chronic mild unpredictable stress in rats are partially attenuated by positive modulation of α5 GABAA receptors","authors":"Jana Ivanović ,&nbsp;Jovana Aranđelović ,&nbsp;Kristina Jezdić ,&nbsp;Branka Divović Matović ,&nbsp;Ivan Jančić ,&nbsp;Bojan Batinić ,&nbsp;Dishary Sharmin ,&nbsp;Prithu Mondal ,&nbsp;James M. Cook ,&nbsp;Miroslav M. Savić","doi":"10.1016/j.pbb.2025.174032","DOIUrl":"10.1016/j.pbb.2025.174032","url":null,"abstract":"<div><div>The response to prolonged mild stress is dichotomous, has been associated with depression, anxiety and cognitive impairment, and may be modulated by various factors such as sex or GABA-ergic transmission. We investigated in rats the sex-dependent effects of four doses of lipopolysaccharide (LPS) in one week, followed by four weeks of chronic unpredictable mild stress (CUMS), on behavioral parameters assessed in the weekly sucrose preference test and spontaneous locomotor activity, as well as in the behavioral battery (elevated-plus-maze test, resident-intruder test, three-chamber test and forced-swim test) conducted after 7 days of treatment with GL-II-73, a positive allosteric modulator selective for α5 GABA_A receptors (LPS/CUMS-GL-II-73), or with solvent (LPS/CUMS-SOL), beginning after the third week of CUMS. At the end of stress, sucrose intake was significantly increased in LPS/CUMS-SOL compared to male controls (CRTL); in females, LPS/CUMS-GL-II-73 showed a significantly higher preference for sucrose than CTRL-SOL. In males, forced swimming time was significantly longer in LPS/CUMS-SOL compared to CTRL-SOL. Social play in the resident-intruder test was reduced in female LPS/CUMS-SOL, and GL-II-73 and GL-II-73 tended to reversed this stress effect. LPS/CUMS-GL-II-73 males showed no significant social recognition in the three-chamber test. Ex vivo tests showed an increase in <em>Gabra5</em> gene expression in the ventral hippocampus in LPS/CUMS-GL-II-73 compared to CTRL-SOL. The subtle changes in the measured parameters suggest that the clinical benefit of positive modulation of α5 GABA_A receptors may result from focusing on the sex-specific niches of behavioral domains affected by prolonged stressors.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174032"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reward contamination in restrictive anorexia nervosa: A meta-analysis of functional MRI studies","authors":"Charlotte S. Rye ,&nbsp;Felippe E. Amorim ,&nbsp;Laetitia H.E. Ward ,&nbsp;Amy L. Milton","doi":"10.1016/j.pbb.2025.174031","DOIUrl":"10.1016/j.pbb.2025.174031","url":null,"abstract":"<div><div>Individuals with anorexia nervosa (AN) are typically anhedonic, leading to the suggestion that intrinsic disturbances of reward processing may represent a trait marker of the disorder. Previous studies have used task-based functional magnetic resonance imaging (fMRI) to investigate reward-related brain activity in AN and reported altered activation in the prefrontal cortex, dorsal posterior cingulate cortex, and rostral anterior cingulate cortex. However, likely due to the varied paradigms and methodologies used, as well as the heterogeneity in sample characteristics, results have proved inconsistent. To determine whether AN patients with the restrictive subtype (AN-r) show different reward-induced activation patterns to matched healthy controls (HCs) at different illness stages, we conducted a meta-analysis of 19 task-based fMRI studies of reward-processing. Using the seed-based differential mapping (SDM) technique, we found differences in reward-related brain activity between AN-r and HCs. Moreover, different brain regions showed differential activation across illness stages, with the direction and magnitude of effects dependent on specific task stimuli. These findings suggest that those with AN-r show distorted reward processing as a consequence of reward contamination and alterations in valence assignment to reward stimuli. In weight-recovered AN-r patients, differences to HCs persisted but were limited to regions known to exhibit significant atrophy in AN-r, indicating that altered reward processing is associated with anorectic undernutrition. These findings have implications for developing pharmacological treatments to aid psychological recovery in AN-r.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174031"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postnatal propionic acid exposure disrupts hippocampal agmatine homeostasis leading to social deficits and cognitive impairment in autism spectrum disorder-like phenotype in rats","authors":"Manasi Tadas ,&nbsp;Nitu Wankhede ,&nbsp;Pranali Chandurkar ,&nbsp;Nandkishor Kotagale ,&nbsp;Milind Umekar ,&nbsp;Raj Katariya ,&nbsp;Akash Waghade ,&nbsp;Dadasaheb Kokare ,&nbsp;Brijesh Taksande","doi":"10.1016/j.pbb.2025.174030","DOIUrl":"10.1016/j.pbb.2025.174030","url":null,"abstract":"<div><div>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by a range of symptoms including impaired social interaction and cognitive deficits. Although the exact pathogenesis of ASD is not well established, recent clinical findings suggest a decline in levels of biogenic amine agmatine in autistic patients. The present study was designed to investigate the impact of postnatal propionic acid (PPA) exposure on hippocampal agmatine homeostasis in male rat pups and to explore a new therapeutic intervention for ASD using agmatine as a biological target. PPA is commonly used in experimental models of ASD due to its ability to induce social deficits, cognitive impairments, and stereotyped behaviors, which closely resemble key characteristics of ASD. Male rat pups were administered with PPA via the intrahippocampal route bilaterally (25 μg/0.25 μl per side) on PND-21 to simulate the ASD phenotype, and its subsequent effect on the endogenous agmatinergic system. The influence of agmatine treatment and its endogenous modulation on ASD-like phenotypes was also investigated. Behavioral assessments revealed that PPA exposure reduced sociability and social preference, caused learning and memory impairment in the Morris water maze, increased anxiety-like behavior in the elevated plus maze, and reduced exploratory behavior in the hole board test. Neurochemical analyses showed a decrease in agmatine concentration and an increase in its degrading enzyme agmatinase in the hippocampus. PPA treatment altered the content of GABA, glutamate, TNF-α, IL-6, BDNF, and also resulted in increased astrogliosis and neurotoxicity within the hippocampus. Chronic agmatine treatment and its endogenous modulation ameliorated the behavioral and biochemical disruptions induced by PPA exposure. This study highlights the critical role of hippocampal agmatinergic pathway in the etiopathogenesis of ASD, positioning agmatine as a promising therapeutic target for its treatment.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174030"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crisugabalin, a ligand for the α2δ subunit of voltage-gated calcium channels, exhibits no obvious abuse potential in rodents","authors":"Xiaoli Gou ,&nbsp;Yijiang Liu ,&nbsp;Qidi Ye ,&nbsp;Lingzhi He ,&nbsp;Ying Chen ,&nbsp;Yansheng Dong ,&nbsp;Qingyuan Meng ,&nbsp;Zongjun Shi ,&nbsp;Yao Li ,&nbsp;Yao Lu ,&nbsp;Ju Wang ,&nbsp;Linggao Zeng","doi":"10.1016/j.pbb.2025.174015","DOIUrl":"10.1016/j.pbb.2025.174015","url":null,"abstract":"<div><div>Crisugabalin, a novel third-generation ligand targeting the <em>α2δ</em> subunit of voltage-gated calcium channels, has been approved in China for the treatment of pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Existing research suggests that ligands for the <em>α2δ</em> subunit of voltage-gated calcium channels may carry a risk of abuse. To evaluate the abuse potential of crisugabalin, five well-recognized animal models were utilized in these preclinical studies. Firstly, an intravenous self-administration paradigm was implemented in rats that were self-administering propofol to assess the reinforcing effects of crisugabalin. Secondly, a rat drug discrimination study was employed to determine the pharmacological similarity between crisugabalin and the training drug midazolam. Then, a conditioned place preference (CPP) paradigm in rats was utilized to evaluate the rewarding properties of crisugabalin. After that, a spontaneous withdrawal study was conducted in rats chronically treated with crisugabalin to examine the liability of developing physical dependence. Finally, a mouse pentylenetetrazol-induced convulsion model was used following chronic exposure to crisugabalin to assess its potential for physical dependence. The results indicated that crisugabalin showed no positive reinforcing effects and did not display midazolam-like discriminative stimulus effects. Moreover, crisugabalin did not induce significant CPP in rats and there was no risk of physical dependence in the pentylenetetrazol-induced convulsion model. In the rat spontaneous withdrawal study, crisugabalin demonstrated a very low level of physical dependence. These findings suggest that crisugabalin has minimal to no potential for abuse, thereby establishing itself as a safer option relative to pregabalin and mirogabalin.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174015"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal maternal stress induces increased avoidance behavior in adolescent mice offspring","authors":"Xueyong Yin ,&nbsp;Rui Jiang ,&nbsp;Xiaoyu Liu ,&nbsp;Yiran Liu ,&nbsp;Xiao Liu ,&nbsp;Fei Zhou ,&nbsp;Xi Yu ,&nbsp;Shu Yan ,&nbsp;Yunluo Li ,&nbsp;Yuru Du ,&nbsp;Youdong Li ,&nbsp;Kaoqi Lian ,&nbsp;Ye Zhao ,&nbsp;Haishui Shi","doi":"10.1016/j.pbb.2025.174029","DOIUrl":"10.1016/j.pbb.2025.174029","url":null,"abstract":"<div><div>Defensive behavior is an instinctive response to potential or actual threats, crucial for the survival and reproduction of species. It is influenced by both genetic and environmental factors and undergoes continuous changes throughout an individual's development. Stress, as a significant environmental factor, has a profound and enduring impact on reshaping an individual's behavior, particularly when experienced during early life. However, the effects of early life stress on defensive behavior remain unclear. In this study, defensive behaviors were evaluated in adolescent mice offspring exposed to prenatal stress. Serum corticosterone and neural dendritic spine density were measured. Behaviors results showed that prenatal stress significantly increased anxiety-like and avoidance behaviors in male offspring mice. Enzyme-linked immunosorbent assay (ELISA) results indicated that prenatal stress led to a significant increase in serum corticosterone levels in male offspring following predator odor exposure. Golgi staining analysis revealed a decrease in neural dendritic spine density in the medial prefrontal cortex (mPFC) of offspring. These findings suggest that behavioral changes in offspring mice caused by prenatal stress may be related to alterations in corticosterone levels and neuronal structure. However, the causation and specific mechanisms require further investigation.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174029"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-acetylcysteine enhances the antipsychotic effect of aripiprazole in the neurodevelopmental rat model of schizophrenia","authors":"Zofia Rogóż ,&nbsp;Kinga Kamińska ,&nbsp;Agnieszka Wąsik","doi":"10.1016/j.pbb.2025.174028","DOIUrl":"10.1016/j.pbb.2025.174028","url":null,"abstract":"<div><div>Symptoms of schizophrenia are well characterized, but the mechanism underlying the pathogenesis of the disease still remains unknown. In addition, therapy of negative symptoms and cognitive deficits in schizophrenic patients is a serious clinical problem. Some clinical studies have shown that the atypical antipsychotic drug aripiprazole (ARI), and the antioxidant <em>N</em>-acetylcysteine (NAC) are effective in reducing positive and negative symptoms of schizophrenia in patients. The aim of the present study was to evaluate the influence of repeated co-treatment with low doses of ARI and NAC on the schizophrenia-like behavior in adult rats. The schizophrenia-like behavior was induced in Sprague-Dawley male pups in the neonatal days p5-p16 by repeated administration of the glutathione synthesis inhibitor L-butionine-(<em>S,R</em>)-sulfoximine (BSO) given together with the dopamine reuptake inhibitor 1-[2-[Bis-4(fluorophenyl)methoxy]ethyl]-4–3-(3-phenylpropyl) (GBR 12909). Adult rats received repeated co-treatment with ARI (0.1 mg/kg) and NAC (10 mg/kg) for 21 days, and their effects on schizophrenia-like behavior were assessed (on p90–91) using the social interaction test and novel object recognition test. The present data indicated that the studied drugs at higher doses: ARI (0.3 mg/kg but not 0.1 mg/kg) and NAC (30 mg/kg but not 10 mg/kg) reversed schizophrenia-like symptoms in the tested model. Moreover, repeated co-treatment with low doses of ARI with NAC also reversed schizophrenia-like behavior in the neurodevelopmental rat model of schizophrenia. The above results indicated that NAC enhanced the action of ARI in the used neurodevelopmental rat model of schizophrenia, and the mechanism of action of the used drugs in this model is discussed.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174028"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}