FURTHER EVIDENCE FOR INTERACTION BETWEEN ANGIOTENSIN-II AND DOPAMINE-RECEPTORS (EXPERIMENTS ON APOMORPHINE STEREOTYPY)

The present study was undertaken to further evaluate the effects of an giotensinergic agents: angiotensin II (AII), its analogues sarmesin ([ Sar(1), Tyr(Me)(4)]AII) and sarilesin ([Sar(1),Ile(8)]AII), as well as DuP 753, a nonpeptide selective AT(1) receptor antagonist, on apomorp hine stereotypy in rats thus providing further evidence for AII-DAergi c receptor interactions. All drugs were administered intracerebroventr icularly (i.c.v.). Stereotyped behavior was evoked by an i.p. injectio n of 3 mg/kg apomorphine. AII (0.1-5 mu g) exerted a decrease on stere otypies (U-shaped); the effect being significant at doses of 1 and 2 m u g. Sarmesin significantly increased apomorphine stereotypy at a dose of 5 mu g and decreased it at a dose of 20 mu g. Sarmesin (10 mu g) r eversed the decreasing effect of AII (2 mu g) leading to a more pronou nced increase of stereotypies. Sarmesin (5 mu g), which by itself is i nactive, also demonstrated antagonistic properties when injected 5 min before AII (2 mu g). DuP 753 (100 mu g) alone had no significant effe ct on apomorphine stereotypy but injected 5 min before AIl (2 mu g) it reversed the decreasing effect of AII on stereotypy. Taken together t he results further confirm the hypothesis that AII closely interacts w ith DAergic neurotransmission, an effect which is mediated predominant ly by AT(1) receptors. (C) 1998 Prous Science. All rights reserved.