MODULATION OF MOTOR FUNCTIONS INVOLVING THE DOPAMINERGIC SYSTEM BY AT(1) RECEPTOR ANTAGONIST, LOSARTAN

Growing evidence has indicated the existence of a brain renin angioten sin system and its possible interaction with other putative neurotrans mitters and their receptors. In the present study, the effect of losar tan, an AT(1) receptor antagonist, was studied on the motor functions involving the dopaminergic system. Losartan (5-30 mg/kg) per se decrea sed locomotor activity without producing motor toxicity. It partially reversed the apomorphine-induced hyperlocomotion and stereotypy in mic e, and potentiated neuroleptic-induced catalepsy in rats. On chronic a dministration (once daily for 21 days) losartan failed to block apomor phine-induced hyperlocomotion, but the inhibition of stereotypic respo nse and potentiation of neuroleptic-induced catalepsy remained unalter ed. These observations suggest that losartan inhibited the release of dopamine through AT(1) receptor and also suggest the existence of a co mpensatory mechanism in certain brain region concerned with dopamine m otor function.