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Neuropharmacology. 2015 Jan;88:36-47. doi: 10.1016/j.neuropharm.2014.06.016. Epub 2014 Jun 24.

GABAB receptors as a therapeutic strategy in substance use disorders: focus on positive allosteric modulators.

Author information

1
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland. Electronic address: mal.fil@if-pan.krakow.pl.
2
Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
3
Department of Pharmacology, Institute of Psychiatry and Neurology, 02-957 Warsaw, Sobieskiego 9, Poland.
4
Alimentary Pharmabiotic Center, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Western Gateway Building, Room 386, Cork, Ireland.

Abstract

γ-Aminobutyric acid B (GABAB) receptors and their ligands are postulated as potential therapeutic targets for the treatment of several brain disorders, including drug dependence. Over the past fifteen years positive allosteric modulators (PAMs) have emerged that enhance the effects of GABA at GABAB receptors and which may have therapeutic effects similar to those of agonists but with superior side-effect profiles. This review summarizes current preclinical evidence supporting a role of GABAB receptor PAMs in drug addiction in several paradigms with relevance to reward processes and drug abuse liability. Extensive behavioral research in recent years has indicated that PAMs of GABAB receptors may have a therapeutic efficacy in cocaine, nicotine, amphetamine and alcohol dependence. The magnitude of the effects observed are similar to that of the clinically approved drug baclofen, an agonist at GABAB receptors. Moreover, given that anxiolytic effects are also reported with such ligands they may also benefit in mitigating the withdrawal from drugs of abuse. In summary, a wealth of data now supports the benefits of GABAB receptor PAMs and clinical validation is now warranted.

KEYWORDS:

Abuse; Addiction; Discrimination; Drug-seeking behavior; GABA(B) receptors; Reward; Sensitization

[Indexed for MEDLINE]

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