99HRT Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus

摘要

We have studied whether chronic alcohol exposure alters expression and/or function of hippocampal kainite receptors (KA-Rs). Under the support of this award, we demonstrated that interneuronal KA-Rs are among the most ethanol sensitive receptors in the central nervous system (see attached reprints number 1 and 2). Based on these results and those of a previous study with CA3 pyramidal neurons, we expected KA-Rs to be upregulated in response to long-term ethanol exposure. During the last year, we have used the ethanol inhalation route to test this possibility. Unexpectedly, we found that 24 h withdrawal from long term exposure to ethanol vapor produced only small non-significant changes in KA-R subunit levels. Radioligand binding studies also yielded unexpected results. Specifically, 3H- vinylidene KA binding was unaffected in the CA3 region, dentate gyrus and cerebellum but significantly decreased in the colliculi, entorrhinal cortex and pre-frontal cortex. Taken together, these results indicate that hippocampal KA-R are minimally affected by long-term ethanol exposure and suggest that these receptors could be involved in the maintenance of sensitivity to ethanol. During the last year of support (non-cost extension), we will concentrate on characterizing the effect of ethanol on the function of presynaptic KA-Rs in the cA3 region.