A comparison of the effects of chronic nicotine infusion on tolerance to nicotine and cross-tolerance to ethanol in long- and shortsleep mice

Several recent studies suggest that common genes regulate sensitivity to an acute dose of ethanol and nicotine. The studies reported here attempted to determine whether common genes regulate the development of cross-tolerance between these drugs. Long-sleep (LS) and short-sleep (SS) mice, which were selectively bred fro differential sensitivity to ethanol as measured by duration of ethanol-induced anesthesia (sleep time), were used in this study. The mice were infused i.v. with saline (control) or one of several doses of nicotine (0.5-4.0 mg kg1 hr1) for 10 days. The LS mice were more sensitive to the acute actions of nicotine than were the SS and they developed more tolerance to nicotine. LS mice were tolerant to nicotine as measured by all four of the behavioral and physiological tests used but this tolerance was readily seen only after treatment with the highest infusion dose. The SS mice developed some tolerance to nicotin