Mj. Wayner et al., ETHANOL AFFECTS HYPOTHALAMIC NEURONS PROJECTING TO THE HIPPOCAMPUS AND INHIBITS DENTATE GRANULE CELL LTP, Alcohol, 14(1), 1997, pp. 1-7
In previous studies we demonstrated that ethanol inhibition of hippoca
mpal granule cell long-term potentiation (LTP) is mediated by angioten
sin II (AII), and the inhibition can be blocked by losartan, a specifi
c AII receptor antagonist. The purpose of the present study was to dem
onstrate that this low-dose ethanol inhibition of dentate granule cell
LTP induction is mediated by lateral hypothalamic (LH) afferents that
project to the granule cells. In urethane anesthetized rats, we compa
red the effects of ethanol infusion, 6.0 mu l/30 min, by means of an o
pen-ended push-pull type cannula, in both the LH and the dentate gyrus
, on dentate granule cell LTP. Results demonstrate a dose-dependent in
hibition of LTP induction when the LH is perfused that can be blocked
by losartan, 10 mg/kg IP. Four doses of ethanol were used: 5, 10, 20,
and 30 mM. There was no effect when the dentate gyrus was infused with
30 mM ethanol and normal granule cell LTP was observed. Also, these r
esults demonstrate for the first time a low-dose ethanol effect on a p
hysiological function, LTP in a specific neural pathway, directly rela
ted to the anterograde amnesia produced by ethanol on short-term memor
y. Therefore, these data support our hypothesis that ethanol inhibitio
n of LTP induction at the medial perforant path-granule cell synapse c
an be attributed to a presynaptic release of AII and cannot be explain
ed in terms of a direct postsynaptic effect on the granule cells. Copy
right (C) 1997 Elsevier Science Inc.