EVALUATION OF THE DISCRIMINATIVE STIMULUS AND REINFORCING EFFECTS OF GAMMAHYDROXYBUTYRATE (GHB)

Gammahydroxybutyrate (GHB) satisfies many of the criteria for consider ation 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 H-3[MK-801] bindin g 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 admi nistration in rhesus monkeys with PCP self-administration histories, i ts ability to produce heroin- and PCP-like discriminative stimulus eff ects, and for its ability to antagonize cocaine discrimination in rats . The results indicated that GHB (300-7500 mu g/kg per infusion) was n ot self-administered above vehicle control rates, although self-infusi ons occurred at levels sufficient to produce signs indicative of sedat ion. Also, neither heroin nor PCP discriminative stimulus effects gene ralized to injections of GHB up to 300 mg/kg IP, and GHB did not effec tively antagonize the cocaine discriminative stimulus when tested up t o 300 mg/kg IP. These data indicate that GHB is unlike PCP as a reinfo rcer and that neither PCP nor heroin generalize to injections of GHB, nor can injections of GHB attenuate the discriminative stimulus effect s of cocaine.