Endocannabinoid Signaling in the Central Amygdala and Bed Nucleus of the Stria Terminalis: Implications for the Pathophysiology and Treatment of Alcohol Use Disorder. (21st August 2019)

• Record Type: Journal Article
• Authors: Bedse, Gaurav; Centanni, Samuel W.; Winder, Danny G.; Patel, Sachin
• Is Part Of: Alcoholism. Volume 43:Number 10(2019)
• Page Start: 2014
• Page End: 2027
• Publication Date: 2019-08-21
• Subjects: Endocannabinoid -- Extended Amygdala -- Stress -- Cannabis -- Alcohol; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.14159
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : High rates of relapse are a chronic and debilitating obstacle to effective treatment of alcohol use disorder (AUD); however, no effective treatments are available to treat symptoms induced by protracted abstinence. In the first part of this 2‐part review series, we examine the literature supporting the effects of alcohol exposure within the extended amygdala (EA) neural circuitry. In Part 2, we focus on a potential way to combat negative affect associated with AUD, by exploring the therapeutic potential of the endogenous cannabinoid (eCB) system. The eCB system is a potent modulator of neural activity in the brain, and its ability to mitigate stress and negative affect has long been an area of interest for developing novel therapeutics. This review details the recent advances in our understanding of eCB signaling in 2 key regions of the EA, the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST), and their role in regulating negative affect. Despite an established role for EA eCB signaling in reducing negative affect, few studies have examined the potential for eCB‐based therapies to treat AUD‐associated negative affect. In this review, we present an overview of studies focusing on eCB signaling in EA and cannabinoid modulation on EA synaptic activity. We further discuss studies suggesting dysregulation of eCB signaling in models of AUD and propose that pharmacological augmentation of eCB could be a novel approach to treat aspects of AUD. Lastly, future directions are proposed to advance our understanding of the relationship between AUD‐associated negative affect and the EA eCB system that could yield new pharmacotherapies targeting negative affective symptoms associated with AUD. Abstract : In ethanol (EtOH) abstinence, 2‐AG levels are decreased, resulting in increased glutamate release and firing of CeA and BNST neurons. Activation of CeA and BNST neurons further activates downstream brain nuclei involved in the brain stress system regulating the negative affective state. EtOH reinstatement normalizes this over activation of CeA and BNST by elevating 2‐AG synthesis. Dysregulated of 2‐AG signaling appears to be critical for negative affective behaviors and excessive ethanol consumption.