A comparison of the effects of chronic nicotine infusion on tolerance to nicotine and cross-tolerance to ethanol in long- and short-sleep 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 for 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 kg-1 hr-1) 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 nicotine but this effect was less than that seen in the LS, was restricted to two of the tests (Y-maze crosses and body temperature) and was seen only after treatment with the 4.0-mg kg-1 hr-1 dose of nicotine. The LS mice developed cross-tolerance to ethanol as measured by the Y-maze crosses and the heart rate and body temperature tests. Cross-tolerance to ethanol was not seen in the LS mice for the Y-maze rears and sleep-time tests. Almost no evidence for cross-tolerance to ethanol was seen in nicotine-infused SS mice.(ABSTRACT TRUNCATED AT 250 WORDS)