SAT2TREATMENT OF ALCOHOL ADDICTION: HOW TO USE SODIUM OXIBATE? (D&A)SAT2.2NEUROBIOLOGY OF GHB IN RELATION TO ALCOHOL DEPENDENCE

• Published in: Alcohol and alcoholism (Oxford) 2011-09, Vol.46 (suppl_1), p.i24-i25
• Main Author: Tabakoff, B
• Format: Article
• Language: English
• ISSN: 0735-0414; 1464-3502
• DOI: 10.1093/alcalc/agr099

The metabolism of GABA in brain generates bioactive metabolites as well as substrates for the tricarboxylic acid cycle (e.g. succinate). The enzyme succinic semialdehyde reductase was discovered in 1974 and was shown to produce gamma hydroxybutyrate (GHB) in brain. GHB had already gained popularity at that time as a xenobiotic with anesthetic properties, and the discovery of the natural production of GHB in brain spurred the search for receptors for the naturally occurring and exogenously administered GHB in brain and other organs. The current evidence indicates that there are two distinct types of receptors for GHB. One is the GABAB receptor dimer, and the other is a GHB-binding protein whose physiological role is still obscure. Both of these 'receptors' are G-protein-coupled receptors exerting their function via interaction with the G sub(i)/G sub(o) protein family. Selective antagonists are available for these receptor types (CGP54626 for the GABAB receptor and NCS-382 for the GHB binding protein) and GABAB receptor null mutant mice have been created. Using these resources, the actions of GHB have been shown to have components that cannot be fully explained only through the GABAB receptor. Interest in the biology of GHB has been increased by both its use as a 'recreational' drug and its more recent application as a treatment for addictive disorders, particularly alcoholism. GHB has been shown to be an effective agent for treating alcohol withdrawal and supporting abstinence over the early period of sobriety, but concern remains about its abuse potential. Recent data on the importance of GABA neurotransmission in genetic predisposition to alcohol consumption, as well as on GHB-induced neuroadaptation which may regulate self-administration of alcohol in animal models, make further inquiry into GHB actions in addiction attractive and necessary. (This study was supported by NIH/NIAAA and the Banbury Fund.)