Discriminative stimulus (DS) properties of nicotine in the C57BL/6 mouse

Previous research conducted in this and other laboratories has examined the role of genetic factors in determining sensitivity to (-)-nicotine in a variety of behavioral and physiological measures in the rat. More recent research further indicates that genetic factors can also influence the level of sensitivity to (-)-nicotine when serving as a discriminative stimulus (DS) in different rat strains. However, there has been little work examining the influence of genotype on the discriminative stimulus (DS) properties of (-)-nicotine in mice, a species that has played a major role in understanding the relationship between genetics and (-)-nicotine pharmacological effects. To further our understanding of the role of genetics and the ability of (-)-nicotine to exert DS control of behavior in the mouse, a group of C57BL/6 mice was trained to discriminate 0.4 mg/kg (-)-nicotine from saline using a two-lever operant procedure. (-)-Nicotine's discriminative stimulus in C57BL/6 mice appears to be similar to that generated in the rat. Results from behavioral tests with other drugs indicated that d-amphetamine exhibited a partial generalization, while (+)-nicotine fully generalized with nicotine. Tests of antagonism with mecamylamine and scopolamine further showed the cholinergic specificity of the (-)-nicotine DS in the mouse; mecamylamine but not scopolamine completely antagonized the (-)-nicotine DS. This work lays the groundwork for future comparisons of different mouse strain's sensitivities to (-)-nicotine's discriminative stimulus as well as using this behavioral model to search for new nicotinic receptor agonists and antagonists.