The molecular basis of alcohol actions in the nervous system is poorly understood. This project studied the molecular structure-function relationships of neuro-transmitter receptors, and the molecular mechanisms of alcohol action on those receptors, using a combination of both molecular biological and electro-physiological techniques. The ethanol sensitivity of GABA-A receptors was studied using GABA-A receptors expressed in Xenopus oocytes. Responses of GABA-A subunits (alpha1)(beta1)(gamma2L) were not affected by ethanol concentrations from 5 to 100 mM, nor were the responses of GABA-A receptors from long-sleep (LS) or short-sleep (SS) mice, which fails to confirm previous reports. The inhibition of non-NMDA glutamate receptors by a series of n-alcohols was studied in Xenopus oocytes expressing GluR1 and GluR3 receptors, and compared to that in hippocampal neurons. Potency for inhibition increased in proportion to chain-length, but inhibition was not observed with 1-octanol for GluR1, 1-nonanol for GluR3, and 1-decanol for the neurons. The observations are consistent with an interaction of the alcohols with a hydrophobic pocket on the receptor protein, and suggest that the size of the pocket may differ on different subunits. The potentiation of nicotinic acetylcholine (nACh) receptors by ethanol was investigated in HEK-293 cells expressing mouse subunits. In cells expressing (alpha)(beta)(gamma)(delta) subunits, ethanol (10-150 mM) potentiated current activated by low ACh concentrations. By contrast, in cells expressing (alpha)(beta)(delta) subunits, ethanol (10-100 mM) did not affect ACh-activated current. The observations suggest that the gamma subunit is required for the ethanol action on these receptors. To localize ethanol's action, the effect of ethanol was studied on nACh(alpha)7 receptors, 5-HT3 receptors, and a chimeric nACh(alpha)7-5-HT3 receptor expressed in Xenopus oocytes. Ethanol (10-100 mM) inhibited nACh(alpha)7 receptors, potentiated 5-HT3 receptors, and inhibited the chimeric receptor in a manner identical to that of nACh(alpha)7 receptors. Since the N-terminal domain of the chimeric receptor was from the nACh(alpha)7 receptor, the observations suggest that the ethanol action is mediated by the N-terminal domain of the receptor.