Maintenance of behavior by ketamine and related compounds in rhesus monkeys with different self-administration histories

Rhesus monkeys lever-pressed under a fixed-ratio 30 time-out 600 sec schedule of i.v. injection of codeine (0.32 mg/kg/injection) or, in a second group of monkeys, ketamine (1.0 mg/kg/injection). During single session substitutions, the maintenance drug was replaced with saline or doses of various other drugs. At appropriate doses, ketamine maintained responding when substituted for codeine and codeine maintained responding when substituted for ketamine. Phencyclidine, dexoxadrol and dextrorphan maintained responding when substituted for ketamine but did not maintain responding when substituted for codeine. Cyclozocine and SKF-10,047 (N-allyl-nor-metazocine) did not maintain responding when substituted for either ketamine or codeine: ethylketazocine did not maintain responding when substituted for ketamine. For those drugs that maintained behavior, fixed-ratio response rate and the number of injections increased to a maximum value with increasing injection dose and then decreased at higher injection doses. Substituted drugs maintained maximum response rates at the following injection doses: codeine, 0.32 mg/kg: ketamine, 1.0 mg/kg: phencyclidine, 0.03 mg/kg, dexoxadrol, 0.32 mg/kg: and dextrorphan, 1.0 mg/kg. Under only the ketamine maintenance schedule, the rate of responding during the timeout component varied as a function of the substitution dose of ketamine, codeine, phencyclidine and dexoxadrol, with the dose that maintained maximal fixed-ratio rates also engendering the highest rates of timeout responding.