Pharmacology Biochemistry and Behavior最新文献

{"title":"Genetic-epigenetic-neuropeptide associations in mood and anxiety disorders: Toward personalized medicine","authors":"Maryam Gilani ,&nbsp;Niloofar Abak ,&nbsp;Mostafa Saberian","doi":"10.1016/j.pbb.2024.173897","DOIUrl":"10.1016/j.pbb.2024.173897","url":null,"abstract":"<div><div>Mood and anxiety disorders are complex psychiatric conditions shaped by the multifactorial interplay of genetic, epigenetic, and neuropeptide factors. This review aims to elucidate the intricate interactions among these factors and their potential in advancing personalized medicine. We examine the genetic underpinnings, emphasizing key heritability studies and specific gene associations. The role of epigenetics is discussed, focusing on how environmental factors can modify gene expression and contribute to these disorders. Neuropeptides, including substance P, CRF, AVP, NPY, galanin, and kisspeptin, are evaluated for their involvement in mood regulation and their potential as therapeutic targets. Additionally, we address the emerging role of the gut microbiome in modulating neuropeptide activity and its connection to mood disorders. This review integrates findings from genetic, epigenetic, and neuropeptide research, offering a comprehensive overview of their collective impact on mood and anxiety disorders. By highlighting novel insights and potential clinical applications, we underscore the importance of a multi-omics approach in developing personalized treatment strategies. Future research directions are proposed to address existing knowledge gaps and translate these findings into clinical practice. Our review provides a fresh perspective on the pathophysiology of mood and anxiety disorders, paving the way for more effective and individualized therapies.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173897"},"PeriodicalIF":3.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472129","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":"Acute exercise performed during the late consolidation phase improves memory persistence by hippocampal protein synthesis and catecholamine modulation","authors":"Karine Ramires Lima,&nbsp;Ana Carolina de Souza da Rosa,&nbsp;Gabriela Cristiane Mendes Gomes,&nbsp;Gabriela Jaques Sigaran,&nbsp;Anna Cecilia Perretto,&nbsp;Pâmela Billig Mello-Carpes","doi":"10.1016/j.pbb.2024.173893","DOIUrl":"10.1016/j.pbb.2024.173893","url":null,"abstract":"<div><div>Memory persistence is a crucial aspect of long-term memory (LTM) and involves late consolidation processes that modulate memory stability over time. Acute physical exercise (PE) has emerged as a potential strategy to modulate memory consolidation and enhance memory persistence. While its effects have been extensively explored in the early consolidation phase, its impact on the late phase remains unexplored. In this study, we investigated the effects and mechanisms of an acute PE on the late consolidation window of novel object recognition (NOR) memory in rats. A 30-minute running session applied 11 h after NOR memory acquisition significantly increased memory persistence for at least 7 days. The inhibition of hippocampal protein synthesis immediately after acute PE using anisomycin (a ribosomal inhibitor) or rapamycin (an mTOR pathway inhibitor) impaired the effect of PE on memory persistence. Animals only presented memory 1 day after acquisition. The same effect was observed with the inhibition of beta-adrenergic receptors by timolol. Although there were no differences between the groups' comparison, blocking D1/D5 receptors after acute PE resulted in a lack of memory persistence in the dichotomous testing (remember/non-remember). Therefore, our exploration of the mechanisms underlying this enhancement revealed the involvement of protein synthesis and the requirement of beta-adrenergic and dopaminergic D1/D5 receptors in the dorsal hippocampus. These findings provide valuable insights into PE as a potential memory modulator, contributing to expanding our understanding of memory consolidation dynamics and acute PE effects.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173893"},"PeriodicalIF":3.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472127","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":"Synaptophysin and GSK-3beta activity in the prefrontal cortex may underlie the effects of REM sleep deprivation and lithium on behavioral functions and memory performance in male rats","authors":"Maryam Gholami-Zanjanbar ,&nbsp;Faezeh Soleimanian ,&nbsp;Niloufar Reyhani ,&nbsp;Shadi Hajizamani ,&nbsp;Amir-Ehsan Sajadi ,&nbsp;Zahra Ghofrani-Jahromi ,&nbsp;Salar Vaseghi","doi":"10.1016/j.pbb.2024.173894","DOIUrl":"10.1016/j.pbb.2024.173894","url":null,"abstract":"<div><div>Rapid-eye movement (REM) stage of sleep serves a critical role in processing cognitive and behavioral functions. Evidence shows that REM sleep deprivation (REM SD) strongly affects the mood state and cognitive abilities. However, there are many inconsistent reports. Although the exact molecular mechanisms underlying REM SD effects have not well been discovered, however, molecular factors including those affected synaptic plasticity and mood state may be involved. There are two important molecular factors that have not been well studied: synaptophysin and glycogen synthase kinase-3 beta (GSK-3beta). The present study aimed to investigate the role of synaptophysin and GSK-3beta in the modulation of memory and behavioral changes induced by REM SD and lithium (as a potent GSK-3beta inhibitor and mood stabilizer). Multiple platform apparatus was used to induce REM SD for 48 h. Lithium was injected at the dose of 50 mg/kg, intraperitoneal (i.p.). Locomotor activity, anxiety-like behavior, pain threshold, novel object recognition memory, and synaptophysin and GSK-3beta level in the prefrontal cortex were evaluated. Results showed REM SD increased locomotor activity, decreased pain threshold, impaired novel object recognition memory, decreased synaptophysin and increased GSK-3beta levels. Lithium reversed these effects. Anxiety-like behavior was unaffected. For the first time, the present study showed that GSK-3beta and synaptophysin may be involved in the modulation of behavior and cognition induced by REM SD and lithium. In conclusion, we suggested that GSK-3beta upregulation and synaptophysin downregulation may underlie the deleterious effects of REM SD, while lithium may counteract REM SD effects via restoring the level of both.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173894"},"PeriodicalIF":3.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446521","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":"Replication and extension of the subregion selectivity of glutamate-related changes within the nucleus accumbens associated with the incubation of cocaine-craving","authors":"Sierra M. Webb ,&nbsp;Bailey W. Miller ,&nbsp;Melissa G. Wroten ,&nbsp;Arianne Sacramento ,&nbsp;Katherine O. Travis ,&nbsp;Tod E. Kippin ,&nbsp;Osnat Ben-Shahar ,&nbsp;Karen K. Szumlinski","doi":"10.1016/j.pbb.2024.173889","DOIUrl":"10.1016/j.pbb.2024.173889","url":null,"abstract":"<div><div>Cue-elicited drug-seeking behavior intensifies with the passage of time during withdrawal from drug taking and this “incubation of cocaine-craving” involves alterations in nucleus accumbens (NA) glutamate transmission. Here, we employed a combination of in vivo microdialysis and immunoblotting approaches to further examine changes in biochemical indices of glutamate transmission within NA subregions that accompany the incubation of cocaine-craving exhibited by male rats with a 10-day history of 6-h access to intravenous cocaine (0.25 mg/infusion). Immunoblotting on whole cell lysates from the core subregion (NAc core) revealed interactions between cocaine self-administration history, withdrawal and drug cue re-exposure for Homer2a/b, mGlu1, and GluN2b expression, as well as indices of Akt and ERK activity. With the exception of PKCε phosphorylation, most protein changes within the shell subregion (NAc shell) depended on drug cue re-exposure and cocaine history rather than varying in a consistent time-dependent manner. Reduced basal extracellular glutamate content was apparent only in the NAc core of cocaine-experienced rats during protracted (30 days) withdrawal and this was accompanied by a markedly blunted capacity of the mGlu1/5 agonist DHPG to elevate glutamate levels within this subregion. Finally, over-expressing neither Homer1c nor Homer2b within the NAc core during protracted cocaine withdrawal altered the magnitude of cue-elicited responding, its extinction or cocaine-primed reinstatement of drug-seeking behavior. The present findings are consistent with the extant literature implicating changes in Group 1 mGlu receptor function within the NAc core subregion as central to incubated cocaine-craving and provide further evidence against a major role for Homer proteins in gating incubated cocaine-craving. Further, our results provide novel correlational evidence implicating elevated Akt and blunted ERK activity within the NAc core as potential contributors to the expression of incubated cocaine-craving, worthy of future investigation.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173889"},"PeriodicalIF":3.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex- and dose-dependent catalase increase and its clinical impact in a benzoate dose-finding, randomized, double-blind, placebo-controlled trial for Alzheimer's disease","authors":"Hsien-Yuan Lane ,&nbsp;Shi-Heng Wang ,&nbsp;Chieh-Hsin Lin","doi":"10.1016/j.pbb.2024.173885","DOIUrl":"10.1016/j.pbb.2024.173885","url":null,"abstract":"<div><h3>Background</h3><div>Sex differences in Alzheimer's disease (AD) are gaining increasing attention. Previously research has shown that sodium benzoate treatment can improve cognitive function in AD patients, particularly in the female patients; and 1000 mg/day of benzoate appears more efficacious than lower doses. Catalase is a crucial endogenous antioxidant; and deficiency of catalase is regarded to be related to the pathogenesis of AD. The current study aimed to explore the role of sex and benzoate dose in the change of catalase activity among benzoate-treated AD patients.</div></div><div><h3>Methods</h3><div>This secondary analysis used data from a double-blind trial, in which 149 CE patients were randomized to receive placebo or one of three benzoate doses (500, 750, or 1000 mg/day) and measured with Alzheimer's disease assessment scale-cognitive subscale. Plasma catalase was assayed before and after treatment.</div></div><div><h3>Results</h3><div>Benzoate treatment, particularly at 1000 mg/day, increased catalase among female patients, but not among male. The increases in the catalase activity among the benzoate-treated women were correlated with their cognitive improvements. In addition, higher baseline catalase activity was associated with more cognitive improvement after benzoate treatment among both female and male patients.</div></div><div><h3>Conclusions</h3><div>Supporting the oxidative stress theory and sex difference in AD, the finding suggest that sex (female) and benzoate dose co-determine catalase increase in benzoate-treated AD patients and the catalase increment contributes to cognitive improvement of benzoate-treated women.</div><div>Trial Registration: <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> Identifier: NCT03752463.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173885"},"PeriodicalIF":3.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392383","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":"Abnormalities in behavior relevant to schizophrenia in embryonic day 17 MAM-exposed rodent models: A systematic review and meta-analysis","authors":"Miao Qi ,&nbsp;Peixin Zhu ,&nbsp;Honglai Wang ,&nbsp;Qi He ,&nbsp;Chunyue Huo","doi":"10.1016/j.pbb.2024.173888","DOIUrl":"10.1016/j.pbb.2024.173888","url":null,"abstract":"<div><h3>Background</h3><div>Neurodevelopmental disorders, notably schizophrenia, present ongoing challenges in mental health. Methylazoxymethanol (MAM), a potent neurodevelopmental disruptor, is implicated in inducing schizophrenia-like structural and functional alterations in rodent models. This study conducts a systematic review and meta-analysis to assess comprehensively the behavioral consequences of embryonic MAM exposure in rodents, focusing on diverse paradigms reflective of schizophrenia-related phenotypes.</div></div><div><h3>Methods</h3><div>Employing a meticulous search strategy across PubMed, Embase, Cochrane Library, Sino Med, CNKI, Weip Database, Wan Fang, and Web of Science, this study adheres to PRISMA guidelines. The analysis includes studies examining the impact of embryonic MAM exposure on behavioral outcomes, such as Prepulse Inhibition (PPI), social interaction (SI), novel object recognition (NOR), elevated plus maze (EPM) performance, and open field test (OFT) results. The study protocol is registered with PROSPERO, number 42024521442 CRD.</div></div><div><h3>Results</h3><div>Involving 19 studies, the meta-analysis reveals nuanced behavioral alterations. MAM-exposed male rats in the EPM group exhibit a Mean Difference of −0.27 (95 % CI: [−1.02, 0.49]) during puberty, with a broader Mean Difference of −0.50 (95 % CI: [−1.97, 0.96]) in adulthood. Combining both stages yields an overall Mean Difference of −0.31 (95 % CI: [−1.01, 0.38]), indicating potential EPM performance differences. Subgroup analysis by MAM dosage levels reveals a Mean Difference of −0.90 (95 % CI: [−1.86, 0.05]) for moderate-dose MAM and 0.65 (95 % CI: [0.29, 1.02]) for high-dose MAM. In the OFT group, adulthood shows a Mean Difference of −1.22 (95 % CI: [−2.14, −0.29]), emphasizing altered exploratory behavior. The NOR group indicates significant Mean Differences of −6.18 (95 % CI: [−8.41, −3.94]) in adulthood, signifying recognition memory deficits. SI assessments show consistent negative Mean Differences during puberty and adulthood for male rats (−1.88 and − 1.87, respectively) and female rats in preestrus and estrus (−1.09).</div></div><div><h3>Conclusions</h3><div>This systematic review and meta-analysis offer a comprehensive overview of behavioral consequences linked to embryonic MAM exposure in rodents. Findings underscore intricate relationships between MAM and various behavioral domains relevant to schizophrenia. Dose-dependent effects, developmental stage considerations, and potential sex-specific influences contribute to the complexity of MAM-induced alterations, advancing our understanding of neurodevelopmental disruptions and suggesting avenues for future research and therapeutic interventions targeting the developmental origins of psychiatric disorders.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173888"},"PeriodicalIF":3.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392380","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":"Ketamine modulates the exploratory dynamics and homebase-related behaviors of adult zebrafish","authors":"Camilla W. Pretzel ,&nbsp;João V. Borba ,&nbsp;Cássio M. Resmim ,&nbsp;Murilo S. De Abreu ,&nbsp;Allan V. Kalueff ,&nbsp;Barbara D. Fontana ,&nbsp;Julia Canzian ,&nbsp;Denis B. Rosemberg","doi":"10.1016/j.pbb.2024.173892","DOIUrl":"10.1016/j.pbb.2024.173892","url":null,"abstract":"<div><div>Anxiety can be a protective emotion when animals face aversive conditions, but is commonly associated with various neuropsychiatric disorders when pathologically exacerbated. Drug repurposing has emerged as a valuable strategy based on utilizing the existing pharmaceuticals for new therapeutic purposes. Ketamine, traditionally used as an anesthetic, acts as a non-competitive antagonist of the glutamate <em>N</em>-methyl-<span>d</span>-aspartate (NMDA) receptor, and shows potential anxiolytic and antidepressant effects at subanesthetic doses. However, the influence of ketamine on multiple behavioral domains in vertebrates is not completely understood. Here, we evaluated the potential modulatory effect of ketamine on the spatio-temporal exploratory dynamics and homebase-related behaviors in adult zebrafish using the open field test (OFT). Animals were exposed to subanesthetic concentrations of ketamine (0, 2, 20, and 40 mg/L) for 20 min and their locomotion-, exploration- and homebase-related behaviors were assessed in a single 30-min trial. Our data revealed that acute ketamine (20 and 40 mg/L) induced hyperlocomotion, as verified by the increased total distance traveled. All concentrations tested elicited circling behavior, a stereotyped-like response which gradually reduced across the periods of test. We also observed modulatory effects of ketamine on the spatio-temporal exploratory pattern, in which the reduced thigmotaxis and homebase activity, associated with the increased average length of trips, suggest anxiolytic-like effects. Collectively, our findings support the modulatory effects of ketamine on the spatio-temporal exploratory activity, and corroborate the utility of homebase-related measurements to evaluate the behavioral dynamics in zebrafish models.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173892"},"PeriodicalIF":3.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392382","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":"Autism spectrum disorder and various mechanisms behind it","authors":"Parisa Rajabi ,&nbsp;Ali Sabbah Noori ,&nbsp;Javad Sargolzaei","doi":"10.1016/j.pbb.2024.173887","DOIUrl":"10.1016/j.pbb.2024.173887","url":null,"abstract":"<div><div>Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental condition characterized by a range of social, communicative, and behavioral challenges. This comprehensive review delves into key aspects of ASD. Clinical Overview and genetic features provide a foundational understanding of ASD, highlighting the clinical presentation and genetic underpinnings that contribute to its complexity. We explore the intricate neurobiological mechanisms at play in ASD, including structural and functional differences that may underlie the condition's hallmark traits. Emerging research has shed light on the role of the immune system and neuroinflammation in ASD. This section investigates the potential links between immunological factors and ASD, offering insights into the condition's pathophysiology. We examine how atypical functional connectivity and alterations in neurotransmitter systems may contribute to the unique cognitive and behavioral features of ASD. In the pursuit of effective interventions, this section reviews current therapeutic strategies, ranging from behavioral and educational interventions to pharmacological approaches, providing a glimpse into the diverse and evolving landscape of ASD treatment. This holistic exploration of mechanisms in ASD aims to contribute to our evolving understanding of the condition and to guide the development of more targeted and personalized interventions for individuals living with ASD.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173887"},"PeriodicalIF":3.3,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392381","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":"(2R,6R)-hydroxynorketamine alleviates PTSD-like endophenotypes by regulating the PI3K/AKT signaling pathway in rats","authors":"Lifen Liu ,&nbsp;Rui Li ,&nbsp;Lanxia Wu ,&nbsp;Yubo Guan ,&nbsp;Miao Miao ,&nbsp;Yuxuan Wang ,&nbsp;Changjiang Li ,&nbsp;Chunyan Wu ,&nbsp;Guohua Lu ,&nbsp;Xinyu Hu ,&nbsp;Lin Sun","doi":"10.1016/j.pbb.2024.173891","DOIUrl":"10.1016/j.pbb.2024.173891","url":null,"abstract":"<div><h3>Background</h3><div>Patients diagnosed with post-traumatic stress disorder (PTSD) mainly exhibit enduring adverse emotions, heightening susceptibility to suicidal thoughts and behaviors. Notably, metabolites of ketamine, particularly (2<em>R</em>,6<em>R</em>)-hydroxyketamine (HNK), have demonstrated favorable antidepressant properties. However, the precise mechanism through which HNK exerts its therapeutic effects on negative emotional symptoms in PTSD patients should be fully elucidated.</div></div><div><h3>Methods</h3><div>In this investigation, a model involving a single prolonged stress and plantar shock (SPS&amp;S) was utilized, followed by the administration of (2<em>R</em>, 6<em>R</em>)-HNK into the lateral ventricle subsequent to the recovery phase. The evaluation of PTSD-related behaviors was conducted through the open field test (OFT), elevated plus maze test (EMPT), and forced swim test (FST). The expression of phosphatidylinositol 3-kinase (PI3K)/phosphokinase B (AKT) signaling pathway in rat brain regions was analyzed using molecular biology experiments.</div></div><div><h3>Results</h3><div>SPS&amp;S rats displayed adverse emotional behaviors characterized by depression and anxiety. Treatment with (2<em>R</em>, 6<em>R</em>)-HNK enhanced exploratory behavior and reversed negative emotional behaviors. This intervention mitigated disruptions in the expression levels of PI3K/AKT signaling pathway-associated proteins in the HIP and PFC, without influencing PI3K/AKT signaling in the AMY of SPS&amp;S rats.</div></div><div><h3>Conclusion</h3><div>Traumatic stress can trigger negative emotional reactions in rats, potentially involving the PI3K/AKT signaling pathway in the HIP, PFC, and AMY. The (2<em>R</em>, 6<em>R</em>)-HNK compounds have demonstrated the potential to mitigate adverse emotions in rats subjected to the SPS&amp;S paradigm. This effect may be attributed to the modulation of the PI3K/AKT signaling pathway in the HIP, and PFC, with a particularly notable impact observed in the HIP region.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173891"},"PeriodicalIF":3.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381404","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":"Developmental 17-OHPC exposure disrupts behavior regulated by the mesocorticolimbic dopaminergic system in rats","authors":"Paige L. Graney ,&nbsp;Michael Y. Chen ,&nbsp;Ruth I. Wood ,&nbsp;Christine K. Wagner","doi":"10.1016/j.pbb.2024.173886","DOIUrl":"10.1016/j.pbb.2024.173886","url":null,"abstract":"<div><div>The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to pregnant individuals with the intention of reducing preterm birth. Although there is evidence that 17-OHPC is likely transferred from mother to fetus, there is little information regarding the potential effects of 17-OHPC administration on behavioral and neural development in offspring. Neonatal 17-OHPC exposure disrupts the development of the mesocorticolimbic dopaminergic pathway and associated behaviors in rats. 17-OHPC exposure altered dopaminergic innervation of prelimbic medial prefrontal cortex (mPFC) in neonates and adolescents and altered performance in measures of decision-making, set-shifting, and reversal-learning tasks. The present study tested the effects of developmental 17-OHPC exposure on numerous cognitive behaviors mediated by the mesocorticolimbic dopaminergic system, such as decision-making in a delay discounting task, latent inhibition following conditioned taste aversion (CTA), and spatial memory in the Morris Water Maze (MWM). The present work also aimed to further investigate response omissions in rats exposed to 17-OHPC during development and the potential role of dopamine D2 receptor in altering omissions in a delay discounting task. 17-OHPC exposure rendered rats less sensitive to an Eticlopride-induced increase in omissions in a delay discounting task when compared to controls. Quinpirole flattened the discount curve in both groups but did not significantly affect omissions in 17-OHPC-exposed or control rats. Following CTA, sucrose-pre-exposed 17-OHPC-exposed rats demonstrated decreased latent inhibition when compared to controls. In Morris Water Maze testing, 17-OHPC-exposed rats did not differ from controls after the first day of testing or during probe testing. These results suggest that exposure to 17-OHPC altered aspects of decision-making and latent inhibition in adult male rats, without affecting performance in a measure of spatial learning and memory. Further, the insensitivity of 17-OHPC-exposed males to an Eticlopride-induced increase in omissions suggests a dysfunction in the D2 receptor following exposure to this clinically used synthetic progestin.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"245 ","pages":"Article 173886"},"PeriodicalIF":3.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378158","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}