An examination of methodological refinements, clozapine and fluphenazine in the anhedonia paradigm

Abstract

Previous work has shown that the reduction in operant response rate in rats treated repeatedly with pimozide is similar to the pattern of decline in rate occasioned by nonreward. This similarity, usually observed with a continuous reinforcement (CRF) schedule, has been interpreted in terms of the neuroleptics' reducing the rewarding quality of the reinforcer, i.e., anhedonia. Although retaining the CRF schedule, the present work departs from earlier methodologies in three major ways: retraining days were not interposed between drug or extinction days; the operant measure, response duration, was used to complement response rate in describing the drug and extinction effects; and, in addition to using pimozide (0.5 and 1.0 mg/kg), two other neuroleptics, clozapine (5.0 and 10.0 mg/kg) and fluphenazine hydrochloride (0.125 mg/kg), were examined in the anhedonia paradigm. Omission of the retraining days still resulted in declines in response rate and increases in response duration that were graphically similar for pimozide and extinction, but were significantly different in degree, with pimozide producing greater reductions in rate and lesser increases in duration than did extinction. Although clozapine, a low-motor-effect neuroleptic, reduced rate and elevated duration, no change was observed for repeated dosing at the 5.0 mg/kg dose level. The 10.0 mg/kg dose yielded a significant across-session increase (i.e., tolerance effect) in rates, an effect entirely the opposite of what would be indicative of anhedonia. Fluphenazine, a high potency, high-motor-effect phenothiazine, did produce a pattern of declining rate and increasing duration across the four days of dosing, and the 0.125 mg/kg of fluphenazine hydrochloride yielded greater effects than 1.0 mg/kg of pimozide. The extinction-like pattern of responding produced by fluphenazine and pimozide, but not by clozapine, suggests that anhedonia per se is insufficient to account for these results and that an as-yet-to-be-elucidated motor and/or associative process is involved.