LONG-TERM ETHANOL AND NICOTINE TREATMENT ELICIT TOLERANCE TO ETHANOL

Several previous studies have shown that 1 to 2 weeks of treatment wit h ethanol elicits tolerance to several effects produced by ethanol and cross-tolerance to nicotine-induced hypothermia. Similarly, short-ter m, high-dose nicotine treatment produces tolerance to nicotine and cro ss-tolerance to ethanol-induced hypothermia. In the studies reported h ere, C57BL/6 mice were force-fed ethanol, nicotine, or an ethanol/nico tine combination in the drinking water for 6 months. All of the chroni c drug-treated mice developed tolerance to ethanol as measured by open -field activity, body temperature, and deep-time tests. Ethanol tolera nce is due, in part, to enhanced metabolism and reduced CNS sensitivit y in the two ethanol-treated groups but only to reduced CNS sensitivit y in the nicotine-treated group, Similar levels of tolerance to nicoti ne developed in those two groups that were nicotine-treated, but no to lerance to nicotine was seen in those animals treated with ethanol alo ne. The tolerance to nicotine may be related to an upregulation of bra in (cortex, hippocampus, and hypothalamus) [H-3]-nicotine binding, but ethanol tolerance is not readily explained by changes in the number o f the brain high affinity nicotine binding sites.