There is a high incidence of smoking among alcoholics; however, the cellular basis of this correlation is not known. Ethanol can potentiate the function of muscle-type nicotinic acetylcholine receptors (nAChR), but the action of ethanol on nAChR in the central nervous system (CNS) is less well understood. We have used whole-cell patch-clamp recording to study the effect of ethanol on nAChR on rat medial habenular nucleus neurons in slice preparations. In the presence of 1 uM atropine, ACh induced a concentration-dependent inward current with an EC50 value of 42 uM. Ethanol (50 mM) produced a 36% reduction of the postsynaptic current induced by 10 uM ACh, an 18% reduction of the current induced by 40 uM ACh, and a 6% reduction of the current induced by 1,000 uM ACh. The effects of additional ethanol concentrations on ACh-induced responses are currently under investigation. RT-PCR analysis was performed on isolated tissue from the rat medial habenular nucleus and it was found that the mRNAs coding for alpha2-4 and beta2-4 nAChR subunits were detected, whereas the mRNAs coding for alpha5-7 nAChR subunits were not detected. Comparison of the effects of ethanol on muscle type nAChR and the nAChR on rat medial habenular nucleus neurons indicates that ethanol can have different effects on the function of nAChR depending on the nAChR subunits that comprise the receptor.
