Effects of ketocyclazocine alone and in combination with naloxone on schedule-controlled responding in squirrel monkeys

A multiple, fixed interval 5 minutes, fixed ratio 30, schedule of food presentation (Mult FI FR) was used to evaluate the effects of ketocyclazocine, a kappa-receptor agonist, in four squirrel monkeys. Two monkeys were initially trained with 1-minute time-out (TO) periods between the components of the multiple schedule and two monkeys were initially trained without these TO periods. Ketocyclazocine dose-response functions were determined for each monkey under their original training conditions and then the conditions were reversed and dose-response functions were re-determined under the new conditions. Ketocyclazocine consistently decreased rates of responding during the FR component of the multiple schedule under both TO and no TO conditions. Under the FI component, ketocyclazocine's effects differed dependent upon dose, conditioning history, and the presence or absence of TO periods. Intermediate doses of ketocyclazocine (0.01-0.056 mg/kg) increased FI rates of responding under the no TO condition in monkeys originally trained under this condition; however, ketocyclazocine did not increase FI rates of responding under the no TO condition in monkeys originally trained under the TO condition. Under the TO condition, intermediate doses of ketocyclazocine did not increase FI rates of responding. High doses of ketocyclazocine (0.1 and 0.17 mg/kg) decreased FI rates of responding in all monkeys under both the TO and no TO conditions Naloxone, in doses up to those which decreased responding when given alone, failed to antagonize completely the rate decreasing effects of ketocyclazocine.