Effects of combined systemic alcohol and central nicotine administration into ventral tegmental area on dopamine release in the nucleus accumbens.
BACKGROUND
Alcoholism is associated with a higher incidence of smoking. The mesolimbic dopaminergic pathway is believed to play an important role in the reinforcing effects of both ethanol and nicotine. This study was undertaken to determine whether simultaneous administration of systemic ethanol and microinjection of nicotine into the ventral tegmental area (VTA) would result in exaggerated release of dopamine (DA) in the shell region of nucleus accumbens.


METHODS
Microdialysis was applied in awake, freely moving adult male Wistar rats, and DA concentration in the dialysate was measured by HPLC-electrochemical detectors.


RESULTS
Systemic administration of ethanol or microinjection of nicotine into VTA resulted in a dose-dependent increase in DA release (extracellular DA concentration). Simultaneous administration of lower doses of nicotine and ethanol resulted in an additive effect on the released DA. This additive effect was not observed with higher doses of nicotine and ethanol. Administration of the nicotinic antagonist mecamylamine into VTA completely blocked ethanol-induced DA release.


CONCLUSIONS
These data support the hypothesis that the reinforcing effects of ethanol are at least partially mediated through the nicotinic receptors in the VTA. Furthermore, administration of selective nicotinic antagonists may be of therapeutic potential in reducing the rewarding effects of ethanol. The data also suggest that the combined effects of ethanol and nicotine on the "reward pathway" may be a contributing factor to the high incidence of smoking in alcoholics.
Tizabi
Yousef
Y
Department of Pharmacology, College of Medicine, Howard University, 520 W Street NW, Washington, DC 20059, USA. ytizabi@howard.edu
Copeland
Robert L
RL
Louis
Vely A
VA
Taylor
Robert E
RE
D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D004338:Drug Combinations; D000431:Ethanol / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage* / Q000819:agonists / Q000037:antagonists & inhibitors; D018722:Nicotinic Agonists / Q000008:administration & dosage; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
D002492:Central Nervous System Depressants; D004338:Drug Combinations; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D000431:Ethanol; D008464:Mecamylamine; D009538:Nicotine; D004298:Dopamine