Abstract

Metabotropic GABAB receptors (GABABRs) mediate slow inhibition and modulate synaptic plasticity throughout the brain. Dysfunction of GABABRs has been associated with psychiatric illnesses and addiction. Drugs of abuse alter GABAB receptor (GABABR) signaling in multiple brain regions, which partly contributes to the development of drug addiction. Recently, GABABR ligands and positive allosteric modulators (PAMs) have been shown to attenuate the initial rewarding effect of addictive substances, inhibit seeking and taking of these drugs, and in some cases, ameliorate drug withdrawal symptoms. The majority of the anti-addiction effects seen with GABABR modulation can be localized to ventral tegmental area (VTA) dopamine neurons, which receive complex inhibitory and excitatory inputs that are modified by drugs of abuse. Preclinical research suggests that GABABR PAMs are emerging as promising candidates for the treatment of drug addiction. Clinical studies on drug dependence have shown positive results with GABABR ligands but more are needed, and compounds with better pharmacokinetics and fewer side effects are critically needed.

Original languageEnglish
Title of host publicationCurrent Topics in Behavioral Neurosciences
PublisherSpringer Science and Business Media Deutschland GmbH
Pages119-155
Number of pages37
DOIs
StatePublished - 2022

Publication series

NameCurrent Topics in Behavioral Neurosciences
Volume52
ISSN (Print)1866-3370
ISSN (Electronic)1866-3389

Keywords

  • Dopamine
  • Positive allosteric modulators (PAMs)
  • Synaptic plasticity
  • Ventral tegmental area (VTA)

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