Effects of clozapine on fixed-consecutive-number responding in rats: A comparison to other neuroleptic drugs

Abstract

The effects of clozapine and several other neuroleptic drugs were examined in rats responding under fixed-consecutive-number (FCN) schedules with minimum response requirements of 4 and 8. Under these schedules, rats were trained to respond either 8 or more times or 4 or more times on one lever, and then respond once on a second lever. In one component of these schedules, an external discriminative stimulus was presented following the completion of the response requirement on the first lever, whereas no stimulus change was programmed under the other. Under the FCN 8 schedule without the external discriminative stimulus, clozapine produced large dose-dependent decreases in accuracy (percent of reinforced response runs), whereas molindone produced small decreases in accuracy. Neither clozapine or molindone, however, altered accuracy under the FCN 4 without the external discriminative stimulus. Under these same schedules, loxapine, chlorpromazine, haloperidol and thioridazine produced small increases in accuracy at intermediate doses without affecting accuracy at the low and high doses. None of the neuroleptics evaluated produced accuracy-altering effects under the FCN schedules with the external discriminative stimulus. In general, all of these drugs decreased response rates in a dose-dependent fashion. The order of potency for the rate-decreasing effects of these drugs was loxapine > haloperidol > molindone > clozapine = chlorpromazine > thioridazine. Thus, the effects of clozapine on accuracy under the FCN schedules without the external discriminative stimulus differed qualitatively from those of other neuroleptic agents.