Haloperidol and clozapine: differential effects on the sensitivity of caudate-putamen neurons to dopamine agonists and cholecystokinin following one month continuous treatment.

The effects of one month continuous treatment with either the typical antipsychotic drug (APD) haloperidol (HAL) or atypical APD clozapine (CLOZ) on the responses of caudate-putamen (CPu) neurons to dopamine (DA) D1 receptor agonist (+)SKF-38393, D2 receptor agonist quinpirole and sulfated cholecystokinin octapeptide (CCK-8S) were compared. The sensitivity of CPu neurons to microiontophoretically applied quinpirole was markedly enhanced in HAL-treated rats; the current (dose)-response curve for quinpirole to suppress the firing activity of CPu cells was shifted significantly to the left as compared to that of saline-treated controls. In addition, in the HAL-treated rats, a higher percentage of CPu neurons responded to quinpirole. In contrast, the responsiveness of CPu cells to quinpirole was not altered in the CLOZ group. Nor was the sensitivity of CPu neurons to selective D1 receptor agonist (+)SKF-38393 changed in APD-treated groups. These results support the view that supersensitive D2 receptors in the CPu may be related to neuroleptic-induced neurological side-effects since the atypical APD CLOZ has low likelihood for causing neurological side-effects and it was ineffective in altering the sensitivity of DA receptor subtypes in the CPu. Interestingly, a greater number of CPu neurons were found to be activated by CCK-8S in CLOZ-treated rats as compared to either the saline-control or HAL group. Whether the enhanced CCK-8S action in the CPu might contribute to CLOZ's low potential for causing neurological side-effects remains to be elucidated.