Evaluation of the discriminative stimulus and reinforcing effects of gammahydroxybutyrate (GHB)

Abstract

Gammahydroxybutyrate (GHB) satisfies many of the criteria for consideration as a neurotransmitter including having specific receptor sites, endogenous synthesis, and heterogeneous CNS distribution. GHB has been reported to be illicitly used, to induce physical dependence, and to relieve effects from alcohol and heroin withdrawal. GHB has also been shown to have antidopaminergic activity to displace ³H[MK-801] binding in brain membranes, and to have some in vivo effects similar to the typical antipsychotics. To characterize the behavioral pharmacology of GHB further, we evaluated it for its reinforcing effects upon IV administration in rhesus monkeys with PCP self-administration histories, its ability to produce heroin- and PCP-like discriminative stimulus effects, and for its ability to antagonize cocaine discrimination in rats. The results indicated that GHB (300–7500 μg/kg per infusion) was not self-administered above vehicle control rates, although self-infusions occurred at levels sufficient to produce signs indicative of sedation. Also, neither heroin nor PCP discriminative stimulus effects generalized to injections of GHB up to 300 mg/kg IP, and GHB did not effectively antagonize the cocaine discriminative stimulus when tested up to 300 mg/kg IP. These data indicate that GHB is unlike PCP as a reinforcer and that neither PCP nor heroin generalize to injections of GHB, nor can injections of GHB attenuate the discriminative stimulus effects of cocaine.