The mesolimbic dopamine-activating properties of ethanol are antagonized by mecamylamine.
It has been suggested that ethanol may interact with the central nicotinic acetylcholine receptor, thus providing a basis for the often observed high consumption of both ethanol and nicotine. In the present in vivo microdialysis study, ethanol (2.5 g/kg) moderately increased dopamine overflow in the rat nucleus accumbens. The central nicotinic acetylcholine receptor antagonist mecamylamine totally counteracted this effect in a dose (1.0 mg/kg) that did not alter dopamine overflow per se. Ethanol also increased the overflow of dihydroxyphenylacetic acid and homovanillic acid, but this effect was not altered by mecamylamine (1.0 mg/kg). Furthermore, the ethanol-induced enhancement of 3,4-dihydroxyphenylalanine accumulation in the mesolimbic dopamine terminal area after NSD 1015 (an inhibitor of l-aromatic amino acid decarboxylase) was completely antagonized by mecamylamine in doses (3.0 and 6.0 mg/kg) that exerted no effects per se. Neither ethanol nor mecamylamine changed the catecholamine synthesis rate in the striatum or the cerebral cortex. These results provide further evidence that ethanol-induced activation of the mesolimbic dopamine system (increased dopamine synthesis and release) may be mediated via stimulation of central nicotinic acetylcholine receptors. It is suggested that antagonists of central nicotinic acetylcholine receptors may be useful in the treatment of alcoholism.
Blomqvist
O
O
Department of Pharmacology, University of Göteborg, Sweden.
Engel
J A
JA
Nissbrandt
H
H
Söderpalm
B
B
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002395:Catecholamines / Q000096:biosynthesis; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D008032:Limbic System / Q000502:physiology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000187:drug effects
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002395:Catecholamines; D006834:Hydrazines; D011950:Receptors, Cholinergic; D015102:3,4-Dihydroxyphenylacetic Acid; D000431:Ethanol; D004295:Dihydroxyphenylalanine; D008464:Mecamylamine; C004297:3-hydroxybenzylhydrazine; D004298:Dopamine; D006719:Homovanillic Acid