The aim of the study was to investigate the importance of the interaction between central dopaminergic and cholinergic mechanisms for ethanol reinforcement. This was done by comparing the effects of nicotine on locomotor activity and release of dopamine in the nucleus accumbens of the alcohol-preferring Alko Alcohol (AA) and alcohol-avoiding alko non-alcohol (ANA) rats. Nicotine was administered acutely (0.25, 0.50 or 0.75 mg/kg, s.c.) or repeatedly once daily (0.5 mg/kg, s.c.) for 8 days. An acute dose of nicotine increased locomotor activity and the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) measured with in vivo microdialysis suggesting stimulation of dopamine release by nicotine. No difference in the stimulation of locomotor activity or in the increase in the extracellular concentrations of dopamine or its metabolites by nicotine was found between the rat lines. The concentrations of nicotine in the plasma were also identical. The rats treated repeatedly with nicotine showed a progressive increase in locomotion. On the challenge day, 1 week after termination of nicotine or saline injections, rats previously treated with nicotine were activated more by nicotine than saline-treated rats. This behavioral sensitization was not accompanied by an increase in the amplitude of the neurochemical response to nicotine, but the duration of the increase in the levels of DOPAC was longer in the nicotine than saline-treated animals. The increases in locomotor activity and metabolite levels were, however, similar in both rat lines. These data suggest that differences in the interaction of central dopaminergic and cholinergic mechanisms probably do not contribute to the difference in ethanol self-administration between the AA and ANA rat lines.