Accumbal dopamine overflow after ethanol: localization of the antagonizing effect of mecamylamine.
It has been suggested that ethanol exerts its mesolimbic dopamine activating effects and its reinforcing effects via interaction with central nicotinic acetylcholine receptors, thus providing a basis for the often observed covariation between ethanol and nicotine consumption. We have previously demonstrated that the central nicotinic acetylcholine receptor antagonist mecamylamine totally counteracts the ethanol-induced elevation of extracellular dopamine in the nucleus accumbens, as measured by in vivo microdialysis. A contribution of peripheral nicotinic receptor blockade could, however, not be excluded. In the present study, mecamylamine (1.0 mg/kg, i.p.) again totally counteracted the ethanol-induced dopamine overflow, as measured by in vivo microdialysis, while the quarternary nicotinic receptor antagonist hexamethonium (10 mg/kg, i.p.) did not. Furthermore, the increase in accumbal dopamine overflow after systemic ethanol (2.5 g/kg, i.p.) was counteracted by local perfusion of mecamylamine (50 microM) in the ipsilateral ventral tegmental area, but not by mecamylamine perfusion in the nucleus accumbens. Ethanol-induced accumbal dopamine overflow was also counteracted by perfusion of hexamethonium (250 microM) in the ventral tegmental area. These results provide further evidence that ethanol-induced activation of the mesolimbic dopamine system is mediated via stimulation of central nicotinic acetylcholine receptors, and that the receptor population within the ventral tegmental area may be the most important in this regard. It is suggested that antagonists of central nicotinic acetylcholine receptors may be useful in the treatment of alcoholism.
Blomqvist
O
O
Department of Pharmacology, Göteborg University, Sweden.
Ericson
M
M
Engel
J A
JA
Söderpalm
B
B
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004336:Drug Antagonism; D000431:Ethanol / Q000494:pharmacology*; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology*; D017551:Microdialysis; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D000431:Ethanol; D008464:Mecamylamine; D004298:Dopamine