GABA(B) Receptors and Alcohol Use Disorders: Preclinical Studies

Abstract

Preclinical research over the past several decades has demonstrated a role for the γ-aminobutyric acid B (GABA B ) receptor in alcohol use disorder (AUD). This chapter offers an examination of preclinical evidence on the role of the GABA B receptor on alcohol-related behaviors with a particular focus on the GABA B receptor agonist baclofen, for which effects have been most extensively studied, and positive allosteric modulators (PAMs) of the GABA B receptor. Studies employing rodent and non-human primate models have shown that activation of the GABA B receptor can reduce (1) stimulating and rewarding effects of alcohol; (2) signs of alcohol withdrawal in rats made physically dependent on alcohol; (3) acquisition and maintenance of alcohol drinking under a two-bottle alcohol versus water choice procedure; (4) alcohol intake under oral operant self-administration procedures; (5) motivational properties of alcohol measured using extinction and progressive ratio procedures; (6) the increase in alcohol intake after a period of alcohol abstinence (the alcohol deprivation effect or ADE); and (7) the ability of alcohol cues and stress to reinstate alcohol seeking when alcohol is no longer available. Baclofen and GABA B PAMs reduce the abovementioned behaviors across different preclinical models, which provides strong evidence for a significant role of the GABA B receptor in alcohol-related behaviors and supports development of medications targeting GABA B receptors for the treatment of AUD. This chapter highlights the value of examining mechanisms of alcohol-related behaviors across multiple animal models to increase the confidence in identification of new therapeutic targets.

Neurotransmitters

• Dopamine
• Endorphins
• GABA (Gamma-Aminobutyric Acid)

Related

• Alcohol