The most commonly abused drugs, alcohol and
nicotine, are likely also the most costly drugs in terms of health and societal costs. A large body of evidence from epidemiological studies indicate that smoking and alcohol-intake are positively correlated. The mesocorticolimbic
dopamine system has been implicated in mediating some of the reinforcing effects of
ethanol, however, the mechanism(s) of action remains to be elucidated; consideration as to
ethanol's ability to interact with
ligand-gated ion channels should be considered. Accumulating evidence from electrophysiological, pharmacological and neurochemical studies suggest that
ethanol may interact with the
nicotinic acetylcholine receptor (nAChR). Thus, it has been shown that the
ethanol-induced stimulation of the mesolimbic
dopamine system and of locomotor activity as well as
ethanol intake and preference in rodents may involve central
nicotinic acetylcholine receptors. Additionally, data has been presented that nAChRs located in the ventral tegmental area may be of particular importance for these effects of
ethanol. Studies aimed at defining the nAChR subpopulation(s) involved in mediating
ethanol-induced locomotor stimulation and accumbal
dopamine overflow as well as
ethanol-intake have revealed that alpha(3)beta(2) or alpha(6) (using
alpha-Conotoxin MII) but not alpha(4)beta(2) (using
dihydro-beta-erythroidine) or alpha(7) (using
methyllycaconitine), could represent targets for developing new drugs in the treatment of
alcoholism. These results do not allow any conclusion as to whether the involvement nAChRs in mediating the effects of
ethanol is direct and/or indirect. With regard to an indirect effect, evidence has accumulated indicating that the
cholinergic excitatory input to the dopaminergic neurons in the ventral tegmental area may be an important part of the neuronal circuits mediating natural as well as
drug-rewarded behavior. The possibility may thus be considered that
ethanol activates the
cholinergic afferents causing a release of
acetylcholine in the ventral tegemental area leading to a stimulation of nAChRs and thereby excite the mesocorticolimbic
dopamine system.