Involvement of transmitter mechanisms in the behavioural effects of angiotensin II.
The behavioural effects of angiotensin II (AT II) were studied using the following paradigms: seizures (threshold and intensity) in mice; active avoidance (shuttle-box) in rats; passive avoidance (step through) in rats; exploratory activity (open field) in rats; apomorphine stereotypy in rats. The involvement of DA- and GABA-ergic transmitter mechanisms in the effects of AT II was also studied. It was found that AT II increased the seizure threshold and decreased the seizure intensity, the effects being potentiated by DA- and GABA-ergic agonists and prevented by DA- and GABA-ergic antagonists. AT II effect on seizure threshold was stronger when AT II was applied after withdrawal of repeatedly injected DA-ergic antagonist pimozide. AT II improved retention in active and passive avoidance tasks. This effect was potentiated by DA- and GABA-ergic agonists. Postrial saralasin and haloperidol abolished the retention-facilitating effect of AT II. Bicuculline and picrotoxin abolished the influence of GABAA-ergic agonists on the memory effect of AT II. AT II changed exploratory behaviour in a nonlinear dose-effect manner. The stimulant effects of AT II were antagonized by saralasin, increased by apomorphine and nomifensine and decreased by haloperidol and alpha-methyl-para-tyrosine (alpha MpT). AT II enhanced apomorphine stereotypy; the effect was decreased by saralasin and alpha MpT, and abolished by haloperidol. These results suggest that the behavioural effects of AT II are mediated by interactions with brain AT II receptors. DA and GABA receptors modulate in some way the AT II activity.
Georgiev
V
V
Department of Experimental Pharmacology, Bulgarian Academy of Sciences, Acad. G. Bonchev, Sofia.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000502:physiology*; D010433:Pentylenetetrazole / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D051381:Rats; D011954:Receptors, Dopamine / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D012640:Seizures / Q000503:physiopathology; D013239:Stereotyped Behavior / Q000187:drug effects
D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D000804:Angiotensin II; D010868:Pimozide; D009118:Muscimol; D001058:Apomorphine; D010433:Pentylenetetrazole