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 va riety of behavioral and physiological measures in the rat. More recent rese arch 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 th e influence of genotype on the discriminative stimulus (DS) properties of ( -)-nicotine in mice, a species that has played a major role in understandin g the relationship between genetics and (-)-nicotine pharmacological effect s. 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 C5 7BL/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 b ut not scopolamine completely antagonized the (-)-nicotine DS. This work la ys the groundwork for future comparisons of different mouse strain's sensit ivities to (-)-nicotine's discriminative stimulus as well as using this beh avioral model to search for new nicotinic receptor agonists and antagonists . (C) 1999 Elsevier Science Inc.