Abstract

The proposed studies will explore biochemical, behavioral, and genetic interactions between ethanol and cholinergic drugs, most notably nicotine and oxotremorine. These studies will attempt to test the hypothesis that some of ethanol's acute and chronic effects are mediated via effects on nicotinic and muscarinic receptors. The experiments will assess the effects of acute and chronic ethanol treatment on nicotinic and muscarinic receptors as well as the effect of altering these receptors on acute response to ethanol, tolerance to ethanol, and the ethanol withdrawal syndrome. A battery of tests has been developed to measure acute responses to ethanol, nicotine, and oxotremorine as well as tolerance to ethanol and the ethanol withdrawal syndrom. Nicotine, scopolamine, or oxotremorine will be infused into LS and SS mice, two selected lines of mice that differ in acute response to ethanol, and the influence of the resultant receptor changes on ethanol response will be measured. In addition, the effects of ethanol, in vitro and in vivo, on cholinergic receptors will be measured. Finally, the genetic control of ethanol/nicotine and ethanol/oxotremorine interactions will be estimated. These studies should provide added insight into the reasons for simultaneous use and abuse of alcohol and nicotine.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA006391-02
Application #
3109553
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1985-06-01
Project End
1988-05-31
Budget Start
1986-06-01
Budget End
1987-05-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Colorado at Boulder
Department
Type
Graduate Schools
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309

  Publications

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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