Effects of the selective angiotensin II receptor antagonists losartan and PD123177 in animal models of anxiety and memory.
There is increasing interest in the potential functional role of the octapeptide angiotensin II (AII) in psychiatric and cognitive disorders. The novel angiotensin II (AII) receptor antagonists, losartan and PD123177, selective for the AT1 and AT2 receptor subtypes respectively, constitute important pharmacological tools for the assessment of the behavioural consequences of modulation of AII function. The present series of studies investigated the effects of each compound in two animal models of anxiety, the rat elevated zero-maze and mouse light/dark box, and two models of working memory in the rat, the operant delayed matching to position (DMTP) task and the spatial reinforced alternation test in the T-maze. Our data indicate that both compounds (0.01-10 mg/kg s.c.) were without significant effect in any of the behavioural assays. Using the present methods and strains of laboratory rodents, these findings provide no support for the involvement of AII receptor function in the mediation of anxiety of working memory.
Shepherd
J
J
Department of Neuropharmacology, Wyeth Research UK Ltd., Berkshire, UK.
Bill
D J
DJ
Dourish
C T
CT
Grewal
S S
SS
McLenachan
A
A
Stanhope
K J
KJ
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D014151:Anti-Anxiety Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D012601:Scopolamine; D019808:Losartan; D003975:Diazepam