Genetic factors are known to affect the reinforcing properties of nicotine. Thus, inbred Lewis rats have been reported to be more sensitive to nicotine compared to Fischer 344 rats in self-administration, conditioned place preference and drug discrimination paradigms. In order to clarify the mechanisms of these differences we investigated, by means of dual probe microdialysis, the effect of different doses of nicotine (0.05, 0.1, 0.2, 0.4 mg/kg s.c.) on dopamine transmission in the shell and in the core of nucleus accumbens. Behavior was monitored during microdialysis. While no differences were observed between strains in dopamine basal values, Lewis rats, compared to Fischer 344 ones, showed in general a larger increase of DA transmission following nicotine both in the shell and in the core of the nucleus accumbens. In regard to behavioral stimulation no differences were observed between strains at higher doses while at the lowest doses Lewis rats appeared more sensitive than Fischer 344 rats to the locomotor stimulating effects of nicotine. These results suggest that strain-related differences in the sensitivity of mesolimbic dopamine transmission to nicotine might be involved in the reported differences in the reinforcing effect of nicotine in Lewis and Fischer 344 rats.
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