Chronic ethanol treatment reduces the magnitude of hippocampal LTD in the adult rat.

Human alcoholics and animals that have received chronic ethanol treatment (CET) display memory deficits. Previous work in our laboratory has shown that CET produces damage to the hippocampus and a reduction in the magnitude of hippocampal long-term synaptic potentiation. In the present report we examined the effects of CET on hippocampal long-term depression (LTD). We used in vitro hippocampal slices to examine LTD after rats received 38-41 weeks of paired feeding on liquid diets containing ethanol or isocaloric sucrose. Stimulation delivered through electrodes in the CA3-CA1 Schaffer collateral pathway activated synaptic population responses in CA1. LTD of CA1 stratum radiatum evoked field potential slope was not induced by 900 single pulses at 1 Hz, but was elicited by 900 pulse pairs separated by 50 or 200 msec delivered at 1 Hz (pLFS50, pLFS200). LTD evoked by pLFS200, but not by pLFS50, was significantly reduced in slices from ethanol-treated rats. The N-methyl D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5) (50 micro M) blocked LTD induced by pLFS50 and pLFS200 equally, but the L-type calcium channel blocker nimodipine (10 micro M) had no effect on either type of LTD. Thus, direct effects on these channels cannot explain how CET selectively reduces the magnitude of pLFS200 LTD. Finally, we describe a novel and robust LTD of the presynaptic afferent volley that is resistant to CET, NMDAR antagonists, GABA-A receptor blockade, and blockade of L-type calcium channels.