IMPAIRED RETENTION BY ANGIOTENSIN-II MEDIATED BY THE AT(1) RECEPTOR

We demonstrated previously that hippocampal dentate gyrus neurons were sensitive to angiotensin II(AII) and recently discovered that AII app lied directly to the dentate gyrus inhibited granule cell long-term po tentiation induction and that the inhibition is mediated by the AT(1) receptor and can be blocked by losartan, a specific AT(1) antagonist. The purpose of the present study was to examine the effects of AII adm inistered directly to the dentate gyrus, 1, 5, 50, 150, and 300 ng, on the retention of an inhibitory shock avoidance response and to determ ine if the resultant impairment of retention can be blocked by losarta n. A total of 12 groups of rats in three experiments were studied. Thr ee 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 pr evented by pretreatment with 20 mg/kg of losartan IP.