Activation of dopamine D2 receptors in the medial shell region of the nucleus accumbens increases Per1 expression to enhance alcohol consumption. (14th January 2022)

• Record Type: Journal Article
• Authors: Sharma, Rishi; Parikh, Meet; Mishra, Vaibhav; Sahota, Pradeep; Thakkar, Mahesh
• Is Part Of: Addiction biology. Volume 27:Number 2(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-14
• Subjects: alcohol -- binge drinking -- D2 receptor -- dopamine -- nucleus accumbens -- Per1; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.13133
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: Circadian genes, including Per1, in the medial shell region of nucleus accumbens (mNAcSh), regulate binge alcohol consumption. However, the upstream mechanism regulating circadian genes‐induced alcohol consumption is not known. Since activation of dopamine D2 receptors (D2R) increases Per1 gene expression, we hypothesised that local infusion of quinpirole, a D2R agonist, by increasing Per1 gene expression in the mNAcSh, will increase binge alcohol consumption in mice. We performed two experiments on male C57BL/6J mice, instrumented with bilateral guide cannulas above the mNAcSh, and exposed to a 4‐day drinking‐in‐dark (DID) paradigm. The first experiment determined the effects of bilateral infusion of quinpirole (100 ng/300 nl/site) or DMSO (Vehicle group) in the mNAcSh on Per1 gene expression and alcohol consumption. The second experiment determined the effect of antisense‐induced downregulation of Per1 in the mNAcSh on the quinpirole‐induced increase in alcohol consumption. Control experiments were performed by exposing the animals to sucrose (10% w/v). After the experiment, animals were euthanised, brains removed and processed for localisation of injection sites and analysis of Per1 gene expression in the mNAcSh. As compared with the DMSO, local bilateral infusion of quinpirole significantly increased the expression of Per1 in the mNAcSh along with an increase in the amount of alcohol consumed in mice exposed to DID paradigm. In addition, local antisense‐induced downregulation of Per1 significantly attenuated the effects of intro‐accumbal infusion of quinpirole on alcohol consumption. Our results suggest that Per1 in the mNAcSh mediates D2R activation‐induced increase in alcohol consumption Abstract : Dopamine D2 receptor (D2R) signaling in the nucleus accumbens (NAc) promotes alcohol consumption; however, the underlying mechanism is unclear. In this study, we have shown that local bilateral infusion of quinpirole, a D2R agonist, significantly increased the expression of period 1 (Per1) gene in the medial accumbal shell region (mNAcSh) and increased alcohol consumption. Antisense‐induced downregulation of Per1 significantly attenuated the effects of intra‐accumbal administration of quinpirole on alcohol consumption suggesting that Per1 mediates D2R activation‐induced increase in alcohol consumption.