The present experiments will examine the effects of typical and atypical neuroleptic (i.e., antipsychotic) drugs on operant performance in rats. Traditional screening procedures have emphasized the extrapyramidal motor side effects (seen with typical neuroleptics) to predict the antipsychotic properties (clinical efficacy) of new neuroleptic drugs. However, newer, atypical neuroleptics do not have this motor liability, yet possess antipsychotic efficacy in the clinical setting. While it is known that neuroleptics typically produce a suppression in food-reinforced operant behavior, it remains unclear as to whether this response disruption is the result of a motor deficit or a reduction in the reinforcement efficacy of the reinforcers (i.e., anhedonia), or a combination of both effects. The first goal is to develop operant testing procedures which will distinguish typical from atypical neuroleptics. Both acute and chronic dosing paradigms will be used since the antipsychotic effects of neuroleptics become evident only after several weeks of chronic dosing. The second goal of the present research is to independently assess both motor and hedonic effects of neuroleptic drugs on operant behavior using a variety of measures including the Matching Equation, response duration vs. response rates, and spontaneous motor activity. These measures, along with the use of acute and chronic dosing regimens, along with the use of acute and chronic dosing regimens, will provide operant screening procedures which can distinguish typical from atypical neuroleptics.
| Porter, J H; Villanueva, H F (1988) Assessment of pimozide's motor and hedonic effects on operant behavior in rats. Pharmacol Biochem Behav 31:779-86 |
