ROLE OF ANGIOTENSIN-II AND AT1 RECEPTORS IN HIPPOCAMPAL LTP

Results of a previous study showed that angiotensin II (AII) inhibited the induction of long-term potentiation (LTP) in hippocampal granule cells in response to dorsomedial perforant path stimulation in urethan e-anesthetized rats. The results of present experiments demonstrate a dose-dependent inhibition of LTP induction under the same conditions d ue to ethanol (EtOH) administered by stomach tube and diazepam (DZ) in jected IP. The inhibition of LTP induction by EtOH and DZ can be block ed by saralasin (SAR) applied directly to the dorsal hippocampus and b y lorsartan (DuP 753) administered IP. Lorsartan or a metabolite cross es the blood-brain barrier because it also blocks the inhibition of LT P induction due to AII administration directly into the dorsal hippoca mpus. Lorsartan is a competitive antagonist of the AT1 subtype AII rec eptor. Therefore, the AII and the EtOH and DZ inhibition of LTP induct ion are mediated by the AII subtype receptor AT1. AIII and the AT2 ant agonist PD123319 did not produce any significant effects. These in viv o effects can be reproduced in brain slices and therefore cannot be at tributed to other factors, such as the urethane. In addition, electric al stimulation of the lateral hypothalamus (LH) inhibits LTP induction , and the inhibition can be blocked by SAR. These data on LH stimulati on indicate that LH AII-containing neurons send axons into the hippoca mpus that inhibit the induction of LTP. These results not only provide new information on a neurotransmitter involved in the amnesic effects of benzodiazepines and ethanol-induced memory blackouts, but also tes table-hypotheses concerning recent observations that angiotensin conve rting enzyme (ACE) inhibitors elevate mood and improve certain cogniti ve processes in the elderly.