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.