Discriminative stimulus effects of combinations of pentobarbital and ethanol in rhesus monkeys.

Abstract

Rhesus monkeys (N = 3) were trained in a 2-lever drug discrimination paradigm to discriminate pentobarbital (PB; 10 mg/kg, i.g., 60 min pre-session) from saline. Lever pressing was maintained under a discrete-trials shock avoidance schedule of reinforcement (30 trials/day, 30-s ITI, FR1). Before test sessions, in which responding on either lever was reinforced, the monkeys were injected with PB and ethanol (EtOH), alone or in combination. Administration of PB alone resulted in a dose-related increase (0-100%) in the percentage of responses emitted on the drug-appropriate lever. The mean ED50 for PB was 7.0 mg/kg (95% C.L. = 6.3-7.7 mg/kg). When administered 60 min pre-session, EtOH engendered a dose-related increase in PB appropriate trials and substituted completely for PB at 3.0 g/kg in two monkeys. In the third monkey, EtOH engendered a maximum of 65% PB-appropriate responding at 1.7 g/kg given 30 min pre-session and predominantly saline-appropriate responding at other pretreatment times. The group ED50 for EtOH at the time of maximum effect was 1.9 g/kg (95% C.L. = 1.4-2.5 g/kg). Administration of 0.3 g/kg EtOH in combination with PB had little or no effect on the PB dose effect function (PB ED50 = 6.7 mg/kg) while 1.0 g/kg EtOH shifted the PB dose-effect function to the left in all monkeys, an average of approximately 3-fold (PB ED50 = 2.1 mg/kg). Isobolographic analysis of the effects of the combination revealed that EtOH and PB were dose additive.