Effects of drugs on schedule-controlled behavior in rats during chronic haloperidol administration.

Dose-response curves for haloperidol, phencyclidine, morphine, meperidine and cimetidine were determined in rats trained under a multiple fixed-ratio 30, fixed-interval 5-min schedule of reinforcement. Haloperidol, morphine, meperidine and cimetidine decreased both fixed-ratio and fixed-interval rates of responding. Phencyclidine had a biphasic effect on overall response rates in both components: response rates increased and then decreased as the dose was increased. After these dose-response curve determinations, chronic daily treatment with haloperidol (0.3 mg/kg i.p.), after the behavioral session, was initiated. After 6 weeks of chronic treatment with haloperidol, the dose-response curves were redetermined for all the drugs, while haloperidol continued to be administered after the session. During chronic haloperidol administration, the dose-effect curves for haloperidol, morphine, meperidine and cimetidine were not modified consistently; however, chronic haloperidol treatment enhanced the effects of phencyclidine as shown by a shift of the dose-response curves to the left during both fixed-ratio and fixed-interval components. Four weeks after chronic haloperidol had been discontinued, low doses of haloperidol produced smaller rate-decreasing effects than they had previously.