This project proposes to continue the selective breeding program to develop high (HAS) and low (]LAS) alcohol sensitive rats. The animals have proven useful in elucidating the mechanism by which alcohol depresses the central nervous system. The project has replicated the classic selection for alcohol sensitivity in mice, the short- and long-sleep mice (SS and LS) with a much more closely controlled genetic protocol including replicate and control lines. Rats, originating from a large genetically heterogeneous base population, are selected to have either prolonged or shortened """"""""sleep times (i.e., duration of loss of the righting response) following a standard intraperitoneal dose of alcohol. Six lines, with two replicates in each direction, are maintained, two high sensitivity (HAS), two low sensitivity (LAS) and two control (CAS) lines. The relative effects of ethanol metabolism are assessed by measurement of blood alcohol levels upon recovery of the righting response. Within family selection is used and a minimum of ten families per line are maintained. Proposed new studies include back selection to check completeness of the selection, development of recombinant inbred animals, testing of correlated responses relating to acute tolerance, preference, reinforcement, activity, temperature, neurotensin functions, ganglioside levels, and response to other hypnotic agents.

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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University of Colorado Denver
Schools of Medicine
United States
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Draski, L J; Bice, P J; Deitrich, R A (2001) Developmental alterations of ethanol sensitivity in selectively bred high and low alcohol sensitive rats. Pharmacol Biochem Behav 70:387-96
Draski, L J; Deitrich, R A; Menez, J F (1997) Phenobarbital sensitivity in HAS and LAS rats before and after chronic administration of ethanol. Pharmacol Biochem Behav 57:651-7
Kiefer, S W; Badia-Elder, N E (1997) Taste reactivity in high-alcohol-sensitive and low-alcohol-sensitive rats. Alcohol 14:225-9
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Erwin, V G; Draski, L J; Deitrich, R A (1996) Neurotensin levels and receptors in HAS and LAS rat brains: effects of ethanol. Pharmacol Biochem Behav 54:525-32
Zimatkin, S M; Deitrich, R A (1995) Aldehyde dehydrogenase activities in the brains of rats and mice genetically selected for different sensitivity to alcohol. Alcohol Clin Exp Res 19:1300-6
Liu, Y; Fay, T; Deitrich, R A (1995) Behavioral effects and pharmacokinetics of propofol in rats selected for differential ethanol sensitivity. Alcohol Clin Exp Res 19:874-8
Deitrich, R A; Draski, L J; Baker, R C (1994) Effect of pentobarbital and gaseous anesthetics on rats selectively bred for ethanol sensitivity. Pharmacol Biochem Behav 47:721-5
Deitrich, R A (1993) Selective breeding for initial sensitivity to ethanol. Behav Genet 23:153-62
Menez, J F; Machu, T K; Song, B J et al. (1993) Phosphorylation of cytochrome P4502E1 (CYP2E1) by calmodulin dependent protein kinase, protein kinase C and cAMP dependent protein kinase. Alcohol Alcohol 28:445-51

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