INBRED MOUSE STRAINS VARY IN ORAL SELF-SELECTION OF NICOTINE

Inbred mouse strains differ in sensitivity to a first dose of nicotine and in the development of tolerance to nicotine. The experiments repo rted here used six inbred mouse strains (A, BUB, C3H, C57BL/6, DBA/2, ST/b) that differ in sensitivity to an acute challenge dose of nicotin e to determine whether differences in oral self-selection of nicotine exist. Animals were presented with solutions containing nicotine or ve hicle (water or 0.2% saccharin) and their daily intake of the two flui ds was measured for 4 days starting with a 10 mu g/ml nicotine solutio n. This was followed by sequential 4-day testing with 20, 35, 50, 65, 80, 100, 125, 160, and 200 mu g/ml nicotine solutions. The strains dif fered dramatically in their self-selection of nicotine and in maximal daily dose (mg/kg); the rank order of the strains was C57BL/6> DBA>BUB >A greater than or equal to C3H greater than or equal to ST/b for both the tap water and 0.2% saccharin choice experiments. Correlations be tween nicotine consumption and sensitivity to nicotine, as measured by a battery of behavioral and physiological responses, were also calcul ated. Strain differences in nicotine intake were highly correlated wit h sensitivity to nicotine-induced seizures. As sensitivity to nicotine -induced seizures increases, oral self-selection of nicotine decreases . This finding may suggest that this toxic action of nicotine serves t o limit intake.