GAMMA-HYDROXYBUTYRIC ACID DECREASES INTRAVENOUS COCAINE SELF-ADMINISTRATION IN RATS

Gamma-hydroxybutyric acid (GHB) is an endogenous compound present in m ammalian brain suggested as a putative neurotransmitter, which has bee n shown to affect several aspects of dependence from various classes o f drugs of abuse. In the present study, two sets of experiments were p erformed to investigate the effects of acute pretreatment with GHB on intravenous cocaine self-administration in rats. Tn the first experime nt GHB was administered intragastrically at the doses of 175, 350, and 700 mg/kg to Long-Evans rats trained to self-administer cocaine using nose-poke as operandum. In the second experiment, GHB was administere d intraperitoneally at the doses of 100, 200, and 400 mg/kg to Wistar rats trained to self-administer cocaine intravenously using lever-pres sing as operandum. In both experiments acute pretreatment with GHB sig nificantly and dose dependently reduced cocaine self-administration. T he effectiveness of GHB was similar in both experiments, indicating th at the effect of GHB on cocaine sell-administration is independent of animal strain, route of administration, and type of operant response r equired, These results indicate that GPIB reduces cocaine-seeking beha vior in rats, modulating the acute reinforcing effect of cocaine. The clinical effectiveness of GHB in dependence from various classes of ab used drugs warrants further studies to evaluate the possibility that G PIB might represent a useful therapeutic agent for cocaine addiction i n humans. (C) 1998 Elsevier Science Inc.