Effects of combinations of phencyclidine and pentobarbital on fixed-interval performance in rhesus monkeys

The effects of phencyclidine (PCP, 0.1-.08 mg/kg), pentobarbital (PB, 2-32 mg/kg) and of combinations of these two drugs were determined in rhesus monkeys trained to respond on a fixed-interval 5-min schedule of food presentation. When combinations of PCP and PB were tested, dose-effect functions for PB on overall response rate were shifted to the left relative to those for PB given alone. This effect was dependent on PCP dose: the higher dose of PCP (0.2 mg/kg) shifted the PB dose-effect function further than did the lower dose (0.1 mg/kg). The effects of both drugs alone and in combination depended upon the rate of responding under control conditions. Individual drugs and combinations increased low rates of responding, increasing and then at higher doses decreased intermediate rates of responding and only decreased high rates of responding. Nevertheless, the effects of combinations of PCP and PB were always shifted to the left relative to PB given alone. This interaction was quantified by using isobolograms for those dependent measures that were decreased by the two drugs given alone or in combination. This analysis revealed that the nature of the interaction between PCP and PB depended upon the dose combination and the measure of performance. Relative to the predictions of a dose-addition model, the interaction was quantitatively greater (additive or supra-additive) when the lower dose of PCP was combined with PB.