Impaired retention by angiotensin II mediated by the AT1 receptor.

We demonstrated previously that hippocampal dentate gyrus neurons were sensitive to angiotensin II (AII) and recently discovered that AII applied directly to the dentate gyrus inhibited granule cell long-term potentiation induction and that the inhibition is mediated by the AT1 receptor and can be blocked by losartan, a specific AT1 antagonist. The purpose of the present study was to examine the effects of AII administered directly to the dentate gyrus, 1, 5, 50, 150, and 300 ng, on the retention of an inhibitory shock avoidance response and to determine if the resultant impairment of retention can be blocked by losartan. A total of 12 groups of rats in three experiments were studied. Three independent repetitions of 5 ng AII administered bilaterally to the dentate gyrus demonstrate a clear impairment of retention under these experimental conditions and that the impairment can be effectively prevented by pretreatment with 20 mg/kg of losartan IP.