ETHANOL AFFECTS HYPOTHALAMIC NEURONS PROJECTING TO THE HIPPOCAMPUS AND INHIBITS DENTATE GRANULE CELL LTP

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.