Differential effect of chronic nicotine treatment on nicotinic receptor numbers in various brain regions of mice.

Studies of smoking behavior in human twin pairs indicate that genetic factors may influence whether people do, or do not, smoke. Because the ability to develop tolerance to behavioral and physiological effects of nicotine may regulate nicotine intake, studies of potential genetic influences on tolerance development were carried out using inbred mouse strains that differ in initial (first dose) sensitivity to nicotine. Nicotine-sensitive strains such as the C57BL and DBA strains develop tolerance to nicotine following chronic intravenous infusion of lower doses of nicotine than are required to elicit tolerance to nicotine in the nicotine-resistant strains such as C3H and BUB. Chronic nicotine infusion results in a dose-related increase in binding of [3H]-nicotine to brain membranes in all strains. Differences in this effect were seen among brain regions as well as between the strains. A quantitative autoradiographic analysis of the effects of chronic nicotine infusion on DBA/2 mice, which develop marked tolerance to nicotine, clearly indicates that nicotine binding is affected to various degrees in various brain nuclei. These results are discussed in terms of genetic influences on tolerance development.