GENOTYPE REGULATES THE DEVELOPMENT OF TOLERANCE TO ETHANOL AND CROSS-TOLERANCE TO NICOTINE

The long-sleep (LS) and short-sleep (SS) mouse lines were selectively bred for differential sensitivity to the anesthetic actions of ethanol , but they also differ in sensitivity to nicotine. A recent study sugg ested that the LS mice develop more tolerance to ethanol and cross-tol erance to nicotine than do the SS following chronic ethanol treatment. The studies reported here expand on these previous studies by assessi ng potential tolerance to ethanol and cross-tolerance to nicotine usin g additional behavioral and physiological measures. In addition, the e ffects of chronic ethanol treatment on ethanol and nicotine metabolism were measured. The LS mice developed tolerance to ethanol as measured by effects on open-field activity, body temperature, and sleep time, whereas the SS mice did not develop consistent tolerance to ethanol's effects on any of these measures. Cross-tolerance to nicotine's effect s on open-field activity and body temperature developed, but only in t he LS mice. The ethanol tolerance is likely due to changes in CNS sens itivity to ethanol, but altered elimination of nicotine may explain mu ch of the cross-tolerance to nicotine seen in chronic ethanol-treated LS mice.