15019421 2004 03 15 2004 04 19 2015 11 19 0149-7634 27 8 2004 Jan Neuroscience and biobehavioral reviews Neurosci Biobehav Rev Neurochemical and behavioral studies on ethanol and nicotine interactions. 713-20 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. Larsson Anna A Department of Pharmacology, Göteborg University, Box 431, Göteborg SE-405 30, Sweden. Engel Jörgen A JA eng Journal Article Research Support, Non-U.S. Gov't Review United States Neurosci Biobehav Rev 7806090 0149-7634 0 Central Nervous System Depressants 0 Nicotinic Agonists 0 Receptors, Nicotinic 3K9958V90M Ethanol 6M3C89ZY6R Nicotine IM Animals Behavior, Animal drug effects Brain Chemistry drug effects Central Nervous System Depressants pharmacology Drug Interactions Ethanol pharmacology Humans Ion Channel Gating drug effects Motor Activity drug effects Nicotine pharmacology Nicotinic Agonists pharmacology Receptors, Nicotinic physiology Ventral Tegmental Area drug effects metabolism 85 2004 3 17 5 0 2004 4 20 5 0 200431750 ppublish 15019421 10.1016/j.neubiorev.2003.11.010 S0149763403001519

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