Evaluation of the reinforcing and discriminative stimulus effects of gamma-hydroxybutyrate in rhesus monkeys

Gamma-hydroxybutyrate (GHB) is a metabolite of GABA that is present in the CNS and fulfils at least some of the criteria for a neurotransmitter. Its e ffects are generally similar to those of CNS depressants and include ataxia , sleep and anesthesia. It has also been suggested that GHB is a drug of ab use. The present experiment was designed to evaluate GHB in procedures pred ictive of abuse and dependence potential in rhesus monkeys. Three monkeys w ere surgically prepared with indwelling silicone venous catheters and allow ed to self-administer methohexital or saline in twice-daily experimental se ssions. Other groups of monkeys were trained in drug discrimination paradig ms to discriminate D-amphetamine (AMPH; n = 4), pentobarbital (PB; n = 3) o r triazolam (n = 3) from saline. Another group was maintained on diazepam d aily and trained to discriminate flumazenil from saline (n = 2). GHB (0.01- 10 mg/kg per injection) maintained self-administration marginally above sal ine levels at one dose (3.2 or 10 mg/kg) in two of the three monkeys tested . GHB (1.0-178 mg/kg, subcutaneously (s.c.) or intragastrically (i.g.)) did not reliably substitute as a discriminative stimulus for any of the traini ng conditions. Taken together with previous results, the present experiment suggests that GHB has, at most, low potential for abuse. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.