title: GABAB receptors as a therapeutic strategy in substance use disorders: focus on positive allosteric modulators.
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.
authors: 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.
authors: Małgorzata
authors: M
authors: Filip
authors: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
authors: Małgorzata
authors: M
authors: Frankowska
authors: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
authors: Anna
authors: A
authors: Sadakierska-Chudy
authors: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
authors: Agata
authors: A
authors: Suder
authors: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
authors: Lukasz
authors: L
authors: Szumiec
authors: Department of Pharmacology, Institute of Psychiatry and Neurology, 02-957 Warsaw, Sobieskiego 9, Poland.
authors: Paweł
authors: P
authors: Mierzejewski
authors: Department of Pharmacology, Institute of Psychiatry and Neurology, 02-957 Warsaw, Sobieskiego 9, Poland.
authors: Przemyslaw
authors: P
authors: Bienkowski
authors: Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smętna 12, Poland.
authors: Edmund
authors: E
authors: Przegaliński
authors: Alimentary Pharmabiotic Center, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Western Gateway Building, Room 386, Cork, Ireland.
authors: John F
authors: JF
authors: Cryan
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D002986:Clinical Trials as Topic; D018757:GABA Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018080:Receptors, GABA-B / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D018757:GABA Modulators; D018080:Receptors, GABA-B
keywords: Abuse; Addiction; Discrimination; Drug-seeking behavior; GABA(B) receptors; Reward; Sensitization