Comparison of circling induced by unilateral intrastriatal microinjections of haloperidol, clozapine and CCK-8 in rats.

The existence of the neuropeptide cholecystokinin (CCK) within a subpopulation of central dopamine (DA) neurons has led to speculations that the peptide may serve as an endogenous modulator of DA functions. To test this possibility, the present study examined the pharmacological action of CCK-8 by comparing its effects on DA-mediated circling behavior with those of a typical (haloperidol; HAL) and an atypical (clozapine; CLZ) dopamine antagonist neuroleptic drug. Rats received unilateral intrastriatal infusions of either sulfated CCK-8 (1, 2, or 8 micrograms), HAL (5 micrograms) or CLZ (5 or 20 micrograms) 15 minutes after systemic injection of d-amphetamine (1 mg/kg). Animals were then placed into rotational chambers where the number and direction of complete 360 degree turns was automatically recorded over a 1 hour session. HAL produced strong and almost exclusive ipsilateral circling while the responses after CLZ and CCK-8 were reliably more variable in rotational direction. More specifically, the results suggest that CLZ is only a weak antagonist of behaviors mediated by striatal DA activation while CCK seems to be devoid of antidopaminergic properties in the striatum.