UNLIKE HALOPERIDOL, CLOZAPINE SLOWS AND DAMPENS RATS FORELIMB FORCE OSCILLATIONS AND DECREASES FORCE OUTPUT IN A PRESS-WHILE-LICKING BEHAVIORAL TASK

In order to detect putative differences in the behavioral effects of c lozapine and haloperidol, rats were trained to use a single forelimb t o exert continuous pressure on a force-sensing operandum. Behavior was maintained by presenting a water-filled dipper for consumption only a s long as the force remained above a specified level (the water founta in task). Effects of clozapine (2.0, 4.0, 8.0 mg/kg) and haloperidol ( 0.02, 0.04, 0.08, 0.12 mg/ kg) on the forelimb force oscillations mani fested during the operandum pressing episodes were analyzed with power spectral analysis and other quantitative methods. All rats exhibited force oscillations with a fundamental frequency near 7 Hz. Clozapine s hifted the frequency to lower values (i.e., oscillation slowing), whil e haloperidol shifted oscillations to slightly higher frequencies. Mor eover, clozapine reduced power in the region of the spectrum above 5 H z. In contrast, haloperidol tended to increase power in these regions. Time domain analyses of the force-time waveforms indicated that halop eridol increased force emission during the hold phase of the forelimb response, and clozapine decreased this measure. The results are congru ent with the high extrapyramidal side effects of haloperidol and the l ack of such effects of clozapine in the clinic. In addition, clozapine may have antitremor effects in rats as it does in humans.