EFFECTS OF LOSARTAN ON NEUROLEPTIC-INDUCED CATALEPSY IN MICE

Neuroleptic-induced catalepsy remains a useful method to study central dopaminergic function in rodents. Evidence obtained in several studie s indicates that this phenomenon can be modified by cholinergic, hista minergic and serotonergic manipulation. Angiotensin II is a central ne urotransmitter acting through AT(1) and AT(2) receptors. There are few data on the effect of angiotensinergic drugs on dopaminergic transmis sion. We investigated the effect of losartan, a nonpeptide antagonist of central and peripheral AT(1) receptors, on neuroleptic-induced cata lepsy. Adult male albino mice, 26-35 g, were used. Catalepsy was induc ed with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals by means of a bar test. Losartan (10 or 100 ng/kg) or saline (control; 0.13 ml) was injected intraperitoneally 20 min before H, with each an imal (7 per group) being used only once. Losartan (10 and 100 ng/kg) s ignificantly (P<0.05) potentiated the cataleptic effect of H in compar ison to the control group (e.g. 264 +/- 26 and 299 +/- 68 sec, respect ively, vs 89 +/- 24 sec for the control group, 90 min after H). No dif ferences were demonstrable 120, 150 or 180 min after H. Considering th e high selectivity and the pharmacokinetic properties of losartan, the se data suggest that central angiotensin ATI receptors play a role in neuroleptic-induced catalepsy. However, further studies are necessary to confirm this hypothesis and to clarify the mechanism(s) involved in this process.