The objective of the proposed work is to explain the mechanisms underlying the variation in ethanol preference observed in rats of the same strain, between different strains of rats and in different lines of rats which were selectively bred for differences in ethanol preference. The long term goal is to thus determine possible biomedical interventions to decrease ethanol consumption in humans. Differences in ethanol preference among various individuals may be related to differences in their response to the behavioral activating (and possible euphoric) effects of ethanol, and/or their ability to develop acute tolerance to the depressant (and possible aversive) effects of ethanol. A low rate of ethanol absorption might affect ethanol preference by facilitating the development of acute tolerance to the depressant effects and thereby unmasking the stimulant effects of ethanol. The proposed work aims to examine the roles of 1) acute tolerance, 2) response to the stimulant effect of ethanol and 3) the rate of ethanol absorption in ethanol preference. Three different experimental strategies will be employed to address this questions: 1) a comparative examination of these three factors in rats (intra-strain, between strains and between rats lines) which display differences in ethanol preference, 2) an examination into how behavioral manipulations such as stress and food deprivation, which have been shown to enhance ethanol consumption, might affect these three factors, and 3) an examination of the effects of such agents as opiate agonists an antagonists, and serotonin uptake inhibitors, which have been shown to modify ethanol preference, on these three factors.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Biochemistry, Physiology and Medicine Subcommittee (ALCB)
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Centre for Addiction and Mental Health
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Le, A D; Israel, Y (1994) A simple technique for quantifying intoxication-induced by low doses of ethanol. Pharmacol Biochem Behav 48:229-34
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Le, A D; Mana, M; Quan, B et al. (1992) Differential development of acute tolerance to the motor impairment and anticonvulsant effects of ethanol. Psychopharmacology (Berl) 109:107-11