Combined effects of systemic alcohol and nicotine on dopamine release in the nucleus accumbens shell.
OBJECTIVE
This study was undertaken to determine whether simultaneous administration of both alcohol and nicotine systemically would result in an additive dopamine release in the nucleus accumbens (NACC). Moreover, to also investigate whether nicotinic receptors may be mediating these effects of alcohol and nicotine, the effects of mecamylamine, a nicotinic receptor antagonist was also evaluated.


METHODS
Microdialysis was applied to measure the dopamine overflow in the shell region of NACC. All drugs were administered intraperitoneally. The doses of alcohol ranged from 0.5-2.0 g/kg, and nicotine and mecamylamine 0.25-1.0 mg/kg.


RESULTS
An additive effect of combined alcohol and nicotine on dopamine release was obtained. This effect of alcohol and nicotine was dose-dependently blocked by mecamylamine pre-treatment.


CONCLUSIONS
These findings further support the hypothesis that an additive effect of alcohol and nicotine on the mesolimbic 'reward pathway' may contribute to the high incidence of smoking in alcoholics. Furthermore, nicotinic antagonists can block such effects of combined alcohol and nicotine.
Tizabi
Yousef
Y
Department of Pharmacology, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, USA. ytizabi@howard.edu
Bai
Li
L
Copeland
Robert L
RL
Taylor
Robert E
RE
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D000431:Ethanol; D008464:Mecamylamine; D009538:Nicotine; D004298:Dopamine