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GABAB receptors in reward processes.

Styliani Vlachou¹, Athina Markou

¹Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, California, USA.

Advances in Pharmacology (San Diego, Calif.)

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Area of Science:

Neuroscience
Pharmacology
Addiction Research

Background:

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain.
GABA(B) receptors are widely distributed and play a role in regulating behavior and reward processes.
Altering GABA signaling impacts drug reinforcement and abuse liability.

Purpose of the Study:

To investigate the efficacy of GABA(B) receptor agonists and positive modulators in inhibiting the reinforcing effects of various drugs of abuse.
To compare the therapeutic potential and side-effect profiles of GABA(B) agonists versus modulators for addiction treatment.

Main Methods:

Behavioral studies utilizing procedures such as intracranial self-stimulation, intravenous self-administration, reinstatement, and conditioned place preference in animal models.
Pharmacological manipulation of GABA(B) receptor activity.

Main Results:

Both GABA(B) receptor agonists and positive modulators effectively blocked the reinforcing effects of drugs like cocaine, amphetamine, nicotine, ethanol, and opiates in animal models.
GABA(B) receptor agonists were associated with undesirable side-effects.
GABA(B) receptor positive modulators demonstrated a superior side-effect profile, acting only in the presence of endogenous GABA.

Conclusions:

GABA(B) receptor positive modulators are promising therapeutic candidates for treating various aspects of drug dependence, including initiation, maintenance, and relapse.
These modulators offer a potentially safer alternative to GABA(B) agonists for managing addiction to substances such as cocaine, nicotine, heroin, and alcohol.