Targeting the GABAB Receptor for the Treatment of Substance Use Disorder

Abstract

This chapter reviews the current preclinical research on the significance of central γ-amino butyric acid (GABA)B receptors in substance use disorder (SUD) and the SUD potential pharmacotherapy based on GABAB receptor ligands. We focused on the role of GABAB receptors in the effects of psychostimulants, opioids, and nicotine in various preclinical behavioral models used in drug addiction research. We provide an overview of the neurochemical mechanisms underlying the interactions between GABAB receptors localized to the mesocorticolimbic dopamine system and drugs of abuse. Finally we discuss the efficacy of GABAB receptor agonists in treatment of human drug addicts. On the whole, the presented data provide compelling preclinical evidence that GABAB receptor agonists and positive allosteric modulators may have efficacy in the treatment of SUD, with GABAB receptor positive allosteric modulators having a better pharmacological profile than orthosteric agonists. There is the need for additional clinical studies to ascertain whether preclinical data translate to the human.