Pharmacology Biochemistry and Behavior最新文献

{"title":"Region-specific neuroadaptations of CRF1 and CRF2 expression following heroin exposure in female rats","authors":"Piper Schneider ,&nbsp;Danielle Goldbaum ,&nbsp;Ansh Agarwal ,&nbsp;Ashton Taylor ,&nbsp;Peyton Sundberg ,&nbsp;Eliot L. Gardner ,&nbsp;Robert Ranaldi ,&nbsp;Zhi-Bing You ,&nbsp;Ewa Galaj","doi":"10.1016/j.pbb.2024.173931","DOIUrl":"10.1016/j.pbb.2024.173931","url":null,"abstract":"<div><div>While stress increases vulnerability to development of addiction, the recruitment of corticotropin releasing factor (CRF) with excessive drug use heightens the risk of stress-induced relapse. CRF signaling is transmitted via CRF1 and CRF2 receptors, but the roles of these receptors in heroin self-administration and related neuroadaptations of the CRF system within mesolimbic brain loci are not well understood. In this study, we first investigated the causal role of CRF1 and CRF2 receptors in heroin self-administration. Intracerebroventricular (ICV) microinjections of antalarmin (a CRF1 antagonist) or astressin-2B (a CRF2 antagonist) caused brief, dose-dependent reductions in heroin self-administration in female rats, suggesting that these receptors play a critical role in heroin-motivated behaviors. We then used western blotting to examine neuroadaptive changes to CRF1 and CRF2 receptor expression in key forebrain and midbrain regions associated with opioid addiction. Female Long Evans rats treated with escalating doses of heroin for 16 days demonstrated significantly higher naloxone-precipitated withdrawal symptoms than saline-treated rats. Heroin-treated rats showed a significant decrease in CRF1 receptor protein expression in the ventral tegmental area (VTA) and an increase in the nucleus accumbens (NAc) but no changes in the prefrontal cortex (PFC), insula, dorsal striatum (dSTR), dorsal hippocampus (dHippo), anterior hypothalamus (HYPTH), amygdala, or substantia nigra (SN) as compared to saline-treated rats. After chronic heroin exposure, CRF2 receptor expression was significantly downregulated in the dHippo, VTA and HYPTH but not in the other brain regions we investigated. The results of this study suggest that: (1) CRF1 and CRF2 receptors play an important role in self-administration and (2) heroin exposure may lead to region-specific neuroadaptation of CRF1 and CRF2 receptors. Such neuroadaptations might in part contribute to the continuation of drug use and stress-induced relapse.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173931"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759501","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":"Venlafaxine treatment is associated with improved mood, but not decreased cocaine self-administration, in depressed people who use cocaine.","authors":"Rebecca L Chalmé, Eric Rubin, Suzette M Evans, Margaret Haney, Richard W Foltin","doi":"10.1016/j.pbb.2024.173918","DOIUrl":"10.1016/j.pbb.2024.173918","url":null,"abstract":"<p><p>Individuals seeking treatment for their cocaine use often report depressive systems and nearly half meet criteria for major depressive disorder (MDD). This descriptive study aimed to assess the effects of the antidepressant venlafaxine alone and in combination with gabapentin on depressive symptoms, subjective effects of cocaine, and cocaine self-administration in depressed and non-depressed people who use cocaine. The effects of medication condition on mood and on the effects of smoked cocaine were compared between a group of clinically depressed people who use cocaine (n = 5) and a control group of non-depressed people who use cocaine (n = 5) using laboratory-based measures. In the MDD group, venlafaxine (300 mg/day) was associated with reduced mean Beck Depression Inventory (BDI) scores (35 to <5) and marginally lower ratings of \"good drug effect\" without affecting cocaine \"wanting\" or cocaine (0-50 mg) self-administration. In both groups, venlafaxine treatment increased resting heart rate, systolic pressure, and diastolic pressure. The addition of gabapentin (2400 mg/day) had no effect relative to venlafaxine alone for either group. Conclusions regarding venlafaxine's effectiveness in treating depression in the MDD group are tempered by the lack of a venlafaxine placebo condition and by reductions in BDI scores associated with abstinence prior to venlafaxine administration. Further research is necessary to identify effective treatments for depressed people who use cocaine.</p>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":" ","pages":"173918"},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770991","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":"Fluoxetine treatment reverses chronic stress-induced promotion on Fk506-binding protein 5 expression and multiple effects on glucocorticoid receptor phosphorylation in the paraventricular nucleus of mice","authors":"Bao-Lun Zhu ,&nbsp;Jin-Yan Tang ,&nbsp;Wei-Jia Chen ,&nbsp;Jun-Jie Qian ,&nbsp;Feng Zhang ,&nbsp;Xiao-Ling Zhang ,&nbsp;Ting-ting Chen ,&nbsp;Bo Jiang ,&nbsp;He-Yan Zhao","doi":"10.1016/j.pbb.2024.173916","DOIUrl":"10.1016/j.pbb.2024.173916","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Fluoxetine is widely used as a first-line antidepressant. However, the molecular mechanisms for its antidepressant effects are still not fully understood. Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis is a core pathogenic mechanism contributing to depression, and fluoxetine treatment prevents this dysfunction. The glucocorticoid receptor (GR) is a major negative feedback regulator of the HPA axis, while Fk506-binding protein 5 (Fkbp5) is a negative regulator of the GR signaling. Therefore, we examined the effects of fluoxetine on Fkbp5 and the GR signaling in the hypothalamic paraventricular nucleus (PVN) of depressed mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Mice were exposed to chronic social defeat stress (CSDS), chronic unpredictable mild stress (CUMS), or chronic restraint stress (CRS) with or without fluoxetine treatment (intraperitoneally injected, 20 mg/kg) and examined for changes in depression-like behaviors and HPA axis activity as well as Fkbp5 expression and GR phosphorylation in the PVN. We then examined if adeno-associated virus (AAV)-mediated Fkbp5 overexpression in the PVN affected the antidepressant actions of fluoxetine in mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Fluoxetine treatment significantly mitigated CSDS-, CUMS-, and CRS-induced depression-like behaviors and HPA axis hyperactivity in mice. Subsequent western blotting analyses showed that fluoxetine treatment fully reversed not only chronic stress-induced upregulation of Fkbp5 and CRH but also chronic stress-induced increase in Ser203 phosphorylation and decrease in Ser211 and Ser234 phosphorylation in GR in the PVN. Moreover, quantitative real-time reverse transcription PCR (qRT-PCR) analyses revealed that the enhanced mRNA levels of Fkbp5 and CRH in PVN neurons of mice subjected to CSDS/CUMS/CRS were also notably reversed by fluoxetine administration. Conversely, Fkbp5 overexpression in the PVN significantly eliminated the antidepressant effects of fluoxetine in mice without affecting their locomotor activity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These results together suggest that fluoxetine treatment reverses chronic stress-induced promotion on Fkbp5 expression and multiple effects on GR phosphorylation in the PVN of mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Significance statement&lt;/h3&gt;&lt;div&gt;The selective serotonin reuptake inhibitor fluoxetine (sold as Prozac) is a widely used treatment for depression, but the full spectrum of therapeutic mechanisms is still debated. Recent evidence suggests that these therapeutic mechanisms include suppression of chronic stress-activated hypothalamus–pituitary–adrenal (HPA) axis. The current study presents the first in vivo evidence showing that suppression of HPA axis hyperactivity by fluoxetine treatment involves reversal of glucocorticoid receptor (GR) phosphorylation via modulation of the GR negative regulator Fk506-binding protein 5 (Fkbp5) in the hypothalamic paraventricular nucleus (PVN). ","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"246 ","pages":"Article 173916"},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757490","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":"GW117 induces anxiolytic effects by improving hippocampal functions.","authors":"Ya-Qi Yang, Murezati Tiliwaerde, Na-Na Gao, Wei Gu, Ting-Ting Zhang, Zeng-Liang Jin","doi":"10.1016/j.pbb.2024.173927","DOIUrl":"10.1016/j.pbb.2024.173927","url":null,"abstract":"<p><p>GW117 functions as both an MT1/MT2 receptor agonist and a 5-HT2C receptor antagonist. This study aimed to investigate the anxiolytic effects of GW117 through behavioral assessments, including the open field test and novelty-suppressed feeding test (NSFT) within a chronic unpredictable mild stress (CUMS) model. GW117 was administered via oral gavage for 21 days to evaluate its sustained anxiolytic effects, with behavioral tests including the NSFT, the Vogel-conflict test, and the O-maze test. To explore the underlying mechanisms, we performed Western blot analyses to assess the expression levels of BCL2-Associated X (Bax), cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP). Additionally, BrdU labeling and immunofluorescence staining were used to examine changes in neuronal regeneration and astrocytogenesis. Our results demonstrated that GW117 produced significant anxiolytic effects across all behavioral assays, both in the CUMS model and during long-term administration. Mechanistic studies revealed that GW117 notably increased the expression of BDNF, GFAP, and Bcl-2, while reducing Bax and cleaved caspase-3 levels in the hippocampus of CUMS model rats. Furthermore, the populations of BrdU-positive and GFAP-positive cells were elevated. These findings suggest that GW117 exerts anxiolytic effects, potentially through enhancements in hippocampal function.</p>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":" ","pages":"173927"},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755469","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 cannabidiol treatment reverses behavioral impairments induced by embryonic valproic acid exposure in male mice.","authors":"J F C Pedrazzi, A J Sales, R S M Ponciano, L G Ferreira, F R Ferreira, A C Campos, J E C Hallak, A W Zuardi, E A Del Bel, F S Guimarães, J A Crippa","doi":"10.1016/j.pbb.2024.173919","DOIUrl":"10.1016/j.pbb.2024.173919","url":null,"abstract":"<p><p>Cannabidiol (CBD), the major non-psychotomimetic compound of the Cannabis sativa plant, has shown promising effects in addressing various symptoms associated with autism spectrum disorder (ASD). This neurodevelopmental disorder typically impacts cognitive, behavioral, social communication, and motor skills domains. However, effective treatments for the wide range of symptoms associated with the disorder are limited and may trigger undesirable effects. Embryonic exposure to valproic acid (VPA, 500 mg/kg at 12^° day embryonic age) in rodents is a consolidated environmental model for studying behavioral and molecular characteristics related to ASD. Therefore, this study aimed to evaluate whether acute CBD could reverse behavioral impairments in adult mice (eight weeks) exposed to VPA in the embryonic period in four distinct trials. In independent groups of animals, the following assays were conducted: I) Pre-Pulse Inhibition Test (PPI), II) Marble Burying, III) Social Interaction, IV) Actimeter Test, and V) Novel Object Recognition Test (NOR). In the PPI paradigm, mice exposed to VPA showed PPI impairment, and CBD (30 and 60 mg/kg) reversed this disruption. CBD (60 mg/kg) respectively decreased the number of buried marbles, improved social interaction time, but failed to reduce stereotyped-like movements in the VPA group. In NOR test CBD at both doses reversed the impairment in index of recognition induced in VPA group. These findings suggest that acute CBD administration can ameliorate behavioral impairments associated with ASD in a well-established animal model for studying this neurodevelopmental disorder.</p>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":" ","pages":"173919"},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770981","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":"The role of reward in substance use disorders: Introduction to the special issue.","authors":"Catherine F Moore, William W Stoops","doi":"10.1016/j.pbb.2024.173928","DOIUrl":"https://doi.org/10.1016/j.pbb.2024.173928","url":null,"abstract":"","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":" ","pages":"173928"},"PeriodicalIF":3.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755470","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":"5-HT1B receptor activation produces rapid antidepressant-like effects in rodents","authors":"Erin A. Clark ,&nbsp;Lien Wang ,&nbsp;Taleen Hanania ,&nbsp;Karla Kretschmannova ,&nbsp;Massimiliano Bianchi ,&nbsp;Elizabeth Jagger ,&nbsp;Tingting Hu ,&nbsp;Fugang Li ,&nbsp;Yasir Gallero-Salas ,&nbsp;Kenneth S. Koblan ,&nbsp;Nina Dedic ,&nbsp;Linda J. Bristow","doi":"10.1016/j.pbb.2024.173917","DOIUrl":"10.1016/j.pbb.2024.173917","url":null,"abstract":"<div><div>Ketamine is noted for its rapid onset antidepressant response and effectiveness in patients with treatment resistant depression. While most research has focused on glutamatergic mechanisms, recent studies show that antidepressant-like effects in rodents are dependent upon the serotonergic (5-HT) system and suggest a potential contribution of the 5-HT_1B receptor. In this study we utilized CP-94253 to examine whether 5-HT_1B receptor agonism produces rapid and sustained antidepressant-like effects, focusing on rodent models and treatment approaches commonly used to demonstrate the differentiated response to ketamine. We first confirmed that CP-94253 is a potent 5-HT_1B agonist <em>in vitro</em> and that CP-94253 occupies brain 5-HT_1B receptors at the doses tested. CP-94253 reduced immobility in the mouse forced swim test (FST) and exhibited a prominent antidepressant signature in the mouse-behavior phenotyping platform SmartCube®. When examined 24 h after acute treatment, CP-94253 reduced FST immobility in both naïve rats and in rats receiving chronic interferon alpha treatment. <em>Ex vivo</em> hippocampal long-term potentiation was also enhanced in naïve rats receiving acute CP-94253 treatment, 24 h prior to the recordings. In mice exposed to chronic social defeat stress, antidepressant-like effects in the tail suspension and sucrose preference tests were seen 1 h and 24 h after acute treatment, respectively. Finally, whole brain c-fos imaging in mice showed that CP-94253 modulates neuronal activity in discrete brain regions including the lateral habenula circuit implicated in depression and the ketamine treatment response. Collectively these results support the further investigation of 5-HT_1B agonism as a novel treatment approach for major depressive disorder.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"247 ","pages":"Article 173917"},"PeriodicalIF":3.3,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751304","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":"Myelin Transcription Factor 1 (MyT1) overexpression mitigates social isolation-induced behavioral deficits: Insights into cortical synaptotagmin 1 regulation and antidepressant-like effects","authors":"Amine Bahi ,&nbsp;Jean-Luc Dreyer","doi":"10.1016/j.pbb.2024.173912","DOIUrl":"10.1016/j.pbb.2024.173912","url":null,"abstract":"<div><div>Social isolation (SI) stress is increasingly recognized as a concern, associated with detrimental effects on mood and emotional well-being. Myelin Transcription Factor 1 (MyT1) is known for its pivotal role in nervous system development and mood regulation. This study delves into the potential of MyT1 to mitigate SI-induced behavioral abnormalities in mice. Utilizing a chronic SI model involving neonatal and post-weaning SI, male and female mice were subjected to lentiviral overexpression of MyT1 specifically in the medial prefrontal cortex (mPFC). A battery of behavioral assessments, including novelty-suppressed feeding, sucrose preference, sucrose splash, tape grooming, tail suspension, and forced swim tests, revealed notable antidepressant-like effects in both sexes upon MyT1 overexpression. Enhanced MyT1 expression corresponded with increased feeding initiation, sucrose preference, and self-grooming, alongside decreased immobility time. Importantly, the upregulation of MyT1 was accompanied by a significant reduction in cortical synaptotagmin 1 (Syt1) level. These findings underscore the involvement of MyT1 in mitigating SI-induced depression-like behavior. Moreover, the observed alterations in behavior are closely associated with changes in cortical Syt1 expression, suggesting its potential role as a target for unraveling the molecular mechanisms underlying mood disorders induced by SI. This study sheds light on the intricate interplay between MyT1 and cortical function in modulating responses to SI, paving the way for potential therapeutic interventions targeting these pathways.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"246 ","pages":"Article 173912"},"PeriodicalIF":3.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731591","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":"Anxiety modulators elicit different behavioral outcomes in adult zebrafish: Emphasis on homebase-related parameters and spatio-temporal exploration","authors":"João V. Borba ,&nbsp;Cássio M. Resmim ,&nbsp;Falco L. Gonçalves ,&nbsp;Rossano M. Silva ,&nbsp;Camilla W. Pretzel ,&nbsp;Hevelyn S. Moraes ,&nbsp;Milena D. Sauter ,&nbsp;Denis B. Rosemberg","doi":"10.1016/j.pbb.2024.173914","DOIUrl":"10.1016/j.pbb.2024.173914","url":null,"abstract":"<div><div>Anxiety is an emotion that represents a crucial anticipatory reaction of aversive stimuli, with clinical relevance in cases of disproportional and severe occurrences. Although distinct animal models have contributed to elucidate anxiety-related mechanisms, the influence of anxiogenic and anxiolytic modulations on both locomotion and exploration-related parameters in the open field test (OFT) is not fully elucidated. Here, we aimed to assess the influence of anxiogenic and anxiolytic manipulations on the exploratory dynamics of adult zebrafish (<em>Danio rerio</em>) focusing on homebase-related behaviors. As anxiogenic manipulations, we used the morphine (1.5 mg/L) withdrawal protocol (MOR); 3.5 mL/L conspecific alarm substance (CAS) for 5 min; and 100 mg/L caffeine (CAF) for 15 min. To evoke anxiolytic-like responses, animals were acutely exposed to 0.5 % (<em>v</em>/v) ethanol (ETOH) for 1 h; 100 μg/L fluoxetine (FLU) for 15 min; and 0.006 mg/L clonazepam (CZP) for 10 min. Then, fish were individually exposed to the 30-min OFT trial, with posterior analysis of behavioral activity. While MOR induced hyperlocomotion and increased periphery occupancy, CAS and CAF groups showed higher immobility and increased latency to homebase formation, respectively. Conversely, ETOH and FLU reduced homebase occupancy, supporting anxiolytic-like behaviors, while CZP did not change zebrafish behavior in the OFT. Cluster analysis was used to reconfirm the remarkable similarities and discrepancies between treatments, thus contributing to characterize the distinct responses measured. Overall, our novel data show the relevance of homebase-related analysis as a sensitive tool to reflect affective-like states in zebrafish, providing innovative approaches to unravel the spatio-temporal dynamics of anxiety-like behaviors in vertebrates.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"246 ","pages":"Article 173914"},"PeriodicalIF":3.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710851","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":"The interaction effects between opioidergic and D1-like dopamine receptors in the nucleus accumbens on pain-related behaviors in the animal model of acute pain","authors":"Pariya Shahani ,&nbsp;Hedie Abolghasemi ,&nbsp;Shima Abtin ,&nbsp;Roghayeh Mozafari ,&nbsp;Nooshin Barikrow ,&nbsp;Batool Ghorbani Yekta ,&nbsp;Abbas Haghparast","doi":"10.1016/j.pbb.2024.173911","DOIUrl":"10.1016/j.pbb.2024.173911","url":null,"abstract":"<div><div>The opioidergic and dopaminergic systems play an essential role in processing pain information in the nucleus accumbens (NAc). The present work examined the hypothesis that interaction between opioidergic and D1-like dopamine receptors in the NAc area may influence acute pain-related behaviors. One hundred sixty adult male Wistar rats unilaterally received different doses of the drug solution or vehicle. First, separate groups of animals received different doses of morphine (5, 10, and 25 mmol/0.5 μL) and various doses of SKF38393 (1.5, 3, 6, and 12 mmol/0.5 μL) as opioid and D1-like receptor agonists in the NAc region, respectively. In the second set of experiments, animals got different amounts (1.5, 3, 6, and 12 mmol/0.5 μL) of SCH23390, a D1-like receptor antagonist, before an effective dose of morphine (10 mmol/0.5 μL). In the last experiment, the animals were given naloxone (1.5, 5, and 15 mmol/0.5 μL) before they were given an effective dose of SKF38393 (3 mmol/0.5 μL). The tail-flick test was then used to measure their acute pain threshold. The main findings showed that intra-NAc injection of morphine and SKF38393 alone causes antinociceptive responses. However, the intra-accumbal injection of SCH23390 significantly reduced the antinociceptive responses elicited by intra-NAc morphine. Additionally, intra-NAc naloxone significantly reduced the antinociceptive effects elicited by intra-NAc SKF38393. Interestingly, SCH23390 was more effective in reversing the analgesic effects of morphine (η2 = 0.61) than naloxone in reversing the analgesic effects of SKF38393 (η2 = 0.49). The findings suggest that the opioidergic and dopamine systems in the NAc collaborate to produce pain-relieving effects. This insight could potentially enhance the effectiveness of lower doses of opioids for pain management, ultimately reducing their usage in clinical settings in the future.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"246 ","pages":"Article 173911"},"PeriodicalIF":3.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715878","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}