Alcoholics are very frequently heavy users of tobacco products. In general, as the consumption of ethanol increases, so does tobacco use. During the last few years we have demonstrated that mice that have been selectively bred for differential sensitivity to ethanol, as measured by duration of ethanol-induced sleep-time, also differ in sensitivity to several of the behavioral and physiological effects elicited by a challenge dose of nicotine. These mice, the LS and SS mice, also differ in the development of tachyphylaxis, or behavioral desensitization, to nicotine and they differ in the effects of ethanol on this process. In all cases, the LS are more responsive. Similarly, the LS develop tolerance to nicotine and cross tolerance to ethanol whereas the SS do not, or do so less readily. The proposed studies will further explore the genetic regulation of ethanol and nicotine acute sensitivity, behavioral desensitization and tolerance and cross-tolerance development using the recombinant inbred starins (RI) that have been developed from the LS-SS mice. Rat strains that are being selectively bred for differential sleep-time will also be studied. Biochemical explanations for ethanol-nicotine interactions will be sought. Specifically, brain nicotinic receptors will be measured using autoradiograhpy; the kinetics of desensitization will be studied using in vitro binding methods, and the effects of ethanol on (14C)-2-deoxyglucose uptake will be measured. These studies should prove to be of value in understanding ethanol/nicotine interactions at brain nicotinic receptors as well as identifying brain regions that are affected similarly by these two drugs. The data obtained should prove useful in understanding the interactions between the two substances that are most frequently used by man.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA006391-07
Application #
3109557
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1985-06-01
Project End
1993-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Type
Other Domestic Higher Education
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
Wilson, W R; Collins, A C (1996) Different levels of [3H]MK-801 binding in long-sleep and short-sleep lines of mice. Alcohol 13:315-20
Luo, Y; Marks, M J; Collins, A C (1994) Genotype regulates the development of tolerance to ethanol and cross-tolerance to nicotine. Alcohol 11:167-76
Grady, S R; Marks, M J; Collins, A C (1994) Desensitization of nicotine-stimulated [3H]dopamine release from mouse striatal synaptosomes. J Neurochem 62:1390-8
de Fiebre, N C; de Fiebre, C M; Booker, T K et al. (1994) Bioavailability of ethanol is reduced in several commonly used liquid diets. Alcohol 11:329-35
de Fiebre, C M; Collins, A C (1993) A comparison of the development of tolerance to ethanol and cross-tolerance to nicotine after chronic ethanol treatment in long- and short-sleep mice. J Pharmacol Exp Ther 266:1398-406
Marks, M J; Farnham, D A; Grady, S R et al. (1993) Nicotinic receptor function determined by stimulation of rubidium efflux from mouse brain synaptosomes. J Pharmacol Exp Ther 264:542-52
Collins, A C; Wehner, J M; Wilson, W R (1993) Animal models of alcoholism: genetic strategies and neurochemical mechanisms. Biochem Soc Symp 59:173-91
Cao, W; Burkholder, T; Wilkins, L et al. (1993) A genetic comparison of behavioral actions of ethanol and nicotine in the mirrored chamber. Pharmacol Biochem Behav 45:803-9
Cao, W; Collins, A C (1993) Ethanol effects on 2-deoxyglucose uptake into tissues obtained from LS and SS mice. Alcohol 10:521-7
Collins, A C; Romm, E; Selvaag, S et al. (1993) A comparison of the effects of chronic nicotine infusion on tolerance to nicotine and cross-tolerance to ethanol in long- and short-sleep mice. J Pharmacol Exp Ther 266:1390-7

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