Glucocorticoids attenuate haloperidol-induced catalepsy through adrenal catecholamines.

Abstract

To examine the influence of adrenal secretions on neuroleptic induced catalepsy, we studied the effect of adrenocorticoids, noradrenaline (NA) or adrenaline (AD) on haloperidol (HAL) induced catalepsy in adrenalectomised (ADX) and sham-adrenalectomised (sham-ADX) rats. HAL (1 mg/kg, i.p.) induced a greater degree of catalepsy in ADX rats as compared to sham-ADX rats. Corticosterone (CORT, 1-2 mg/kg, s.c.) or dexamethasone (1-2 mg/kg, s.c.) attenuated the HAL catalepsy in sham-ADX but not in ADX rats. Further, when the HAL (1 mg/kg) catalepsy score was maximal (at 120 min), the rats were subjected to cold stress (3 degrees C for 10 min) or treated with NA, AD (2 micrograms/kg, i.v.) or CORT (2 mg/kg, s.c.). After cold stress procedure or CORT treatment, the catalepsy was significantly reduced in sham-ADX but not in ADX rats, whereas NA or AD infusion caused an immediate but short lasting significant decrease in HAL catalepsy in both sham-ADX and ADX rats. The anticataleptic effect of NA or glucocorticoids was blocked by an alpha 1 adrenoceptor blocker, prazosin. These findings suggest that peripheral noradrenergic and adrenergic mechanisms play an important role in the neuroleptic induced catalepsy. Such mechanisms may mediate the anticataleptic action of glucocorticoids.