EFFECTS OF THE SELECTIVE ANGIOTENSIN-II RECEPTOR ANTAGONISTS LOSARTANAND PD123177 IN ANIMAL-MODELS OF ANXIETY AND MEMORY

There is increasing interest in the potential functional role of the o ctapeptide angiotensin II (AII) in psychiatric and cognitive disorders . The novel angiotensin II (AII) receptor antagonists, losartan and PD 123177, selective for the AT(1) and AT(2) receptor subtypes respective ly, constitute important pharmacological tools for the assessment of t he behavioural consequences of modulation of ATI function. The present series of studies investigated the effects of each compound in two an imal models of anxiety, the rat elevated zero-maze and mouse light/dar k box, and two models of working memory in the rat, the operant delaye d matching to position (DMTP) task and the spatial reinforced alternat ion test in the T-maze. Our data indicate that both compounds (0.01-10 mg/kg SC) were without significant effect in any of the behavioural a ssays. Using the present methods and strains of laboratory rodents, th ese findings provide no support for the involvement of AII receptor fu nction in the mediation of anxiety or working memory.