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 angiotensinergic agents: angiotensin II (AII), its analogues sarmesin ([Sar1, Tyr(Me)4]AII) and sarilesin ([Sar1, Ile8]AII), as well as DuP 753, a nonpeptide selective AT1 receptor antagonist, on apomorphine stereotypy in rats thus providing further evidence for AII-DAergic receptor interactions. All drugs were administered intracerebroventricularly (i.c.v.). Stereotyped behavior was evoked by an i.p. injection of 3 mg/kg apomorphine. AII (0.1-5 micrograms) exerted a decrease on stereotypies (U-shaped); the effect being significant at doses of 1 and 2 micrograms. Sarmesin significantly increased apomorphine stereotypy at a dose of 5 micrograms and decreased it at a dose of 20 micrograms. Sarmesin (10 micrograms) reversed the decreasing effect of AII (2 micrograms) leading to a more pronounced increase of stereotypies. Sarilesin (5 micrograms), which by itself is inactive, also demonstrated antagonistic properties when injected 5 min before AII (2 micrograms). DuP 753 (100 micrograms) alone had no significant effect on apomorphine stereotypy, but injected 5 min before AII (2 micrograms) it reversed the decreasing effect of AII on stereotypy. Taken together, the results further confirm the hypothesis that AII closely interacts with DAergic neurotransmission, an effect which is mediated predominantly by AT1 receptors.
Laboratory of Experimental Psychopharmacology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
J
J
Tchekalarova
V
V
Georgiev
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects*
D011954:Receptors, Dopamine; D000804:Angiotensin II; C009210:sarleucin; C040420:angiotensin II, Sar(1)-Me-Tyr(4)-; D019808:Losartan; D001058:Apomorphine