Ethanol affects hypothalamic neurons projecting to the hippocampus and inhibits dentate granule cell LTP.

In previous studies we demonstrated that ethanol inhibition of hippocampal granule cell long-term potentiation (LTP) is mediated by angiotensin II (AII), and the inhibition can be blocked by losartan, a specific AII receptor antagonist. The purpose of the present study was to demonstrate 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 compared the effects of ethanol infusion, 6.0 microliter/30 min, by means of an open-ended push-pull type cannula, in both the LH and the dentate gyrus, on dentate granule cell LTP. Results demonstrate a dose-dependent inhibition of LTP induction when the LH is perfused that can be blocked by losartan, 10 mg/kg i.p.. 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 results demonstrate for the first time a low-dose ethanol effect on a physiological function, LTP in a specific neural pathway, directly related to the anterograde amnesia produced by ethanol on short-term memory. Therefore, these data support our hypothesis that ethanol inhibition of LTP induction at the medial perforant path-granule cell synapse can be attributed to a presynaptic release of AII and cannot be explained in terms of a direct postsynaptic effect on the granule cells.