• Ethanol;
  • Nicotine;
  • Mesolimbic;
  • Reward Pathway;
  • Microdialysis

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.