Long-term ethanol and nicotine treatment elicit tolerance to ethanol.
Several previous studies have shown that 1 to 2 weeks of treatment with ethanol elicits tolerance to several effects produced by ethanol and cross-tolerance to nicotine-induced hypothermia. Similarly, short-term, high-dose nicotine treatment produces tolerance to nicotine and cross-tolerance to ethanol-induced hypothermia. In the studies reported here, C57BL/6 mice were force-fed ethanol, nicotine, or an ethanol/nicotine combination in the drinking water for 6 months. All of the chronic drug-treated mice developed tolerance to ethanol as measured by open-field activity, body temperature, and sleep-time tests. Ethanol tolerance is due, in part, to enhanced metabolism and reduced CNS sensitivity in the two ethanol-treated groups but only to reduced CNS sensitivity in the nicotine-treated group. Similar levels of tolerance to nicotine developed in those two groups that were nicotine-treated, but no tolerance to nicotine was seen in those animals treated with ethanol alone. The tolerance to nicotine may be related to an upregulation of brain (cortex, hippocampus, and hypothalamus) [3H]-nicotine binding, but ethanol tolerance is not readily explained by changes in the number of the brain high affinity nicotine binding sites.
Collins
A C
AC
Institute for Behavioral Genetics, University of Colorado, Boulder 80309-0447, USA.
Wilkins
L H
LH
Slobe
B S
BS
Cao
J Z
JZ
Bullock
A E
AE
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D004361:Drug Tolerance; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects; D012890:Sleep / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D011978:Receptors, Nicotinic; D000431:Ethanol; D009538:Nicotine