The central research goal of this new program project application is to determine the extent of genetic correlation of sensitivity, tolerance, and withdrawal for several effects of ethanol (EtOH) in mice. Several responses reflecting EtOH's hedonic, sedative, endocrine, and withdrawal effects will be analyzed using behavioral, neuropharmacologically specified mice after acute EtOH to determine the genetic bases for initial sensitivity to EtOH. They will also be studied after repeated administrations of EtOH using different responses and patterns of exposure. The rates of onset and maximal degree of tolerance or sensitization achieved will be estimated. Two methods will be employed to estimate the presence of genetic correlations. First, all component projects will study acute and/or chronic EtOH effects in a battery of 20 Recombinant Inbred (RI) strains, derived from the parental inbred strains C57BL/6J (C57) and DBA/2J (DBA). Common use of this panel of RI strains by all projects will offer several advantages. All projects will be contributing to a central data base which will offer much more information than if similar studies were carried out independently. It will also be possible to detect any potential single gene difference in this data set, and existing indications of single gene differences in the BXD RI panel described above may be followed up in the proposed research. The second method to be employed to estimate genetic correlations will be to study the divergence of selectively bred mouse lines for the presence of correlated responses. Lines selected for three different responses to EtOH (WSP/WSR, HOT/COLD, FAST/SLOW) will be studied. Individual projects will assess one or more of these selected lines to provide convergent validity of any genetic correlations assessed in the BXD RI panel.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Program Projects (P01)
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Special Emphasis Panel (SRCA (70))
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Oregon Health and Science University
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Crabbe, John C; Metten, Pamela; Gallaher, Edward J et al. (2002) Genetic determinants of sensitivity to pentobarbital in inbred mice. Psychopharmacology (Berl) 161:408-16
Mason, J N; Eshleman, A J; Belknap, J K et al. (2001) NMDA receptor subunit mRNA and protein expression in ethanol-withdrawal seizure-prone and -resistant mice. Alcohol Clin Exp Res 25:651-60
Risinger, F O; Cunningham, C L (1998) Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice. Alcohol Clin Exp Res 22:1234-44
Chester, J A; Cunningham, C L (1998) Modulation of corticosterone does not affect the acquisition or expression of ethanol-induced conditioned place preference in DBA/2J mice. Pharmacol Biochem Behav 59:67-75
Crabbe, J C; Gallaher, E J; Cross, S J et al. (1998) Genetic determinants of sensitivity to diazepam in inbred mice. Behav Neurosci 112:668-77
Shen, E H; Dorow, J; Harland, R et al. (1998) Seizure sensitivity and GABAergic modulation of ethanol sensitivity in selectively bred FAST and SLOW mouse lines. J Pharmacol Exp Ther 287:606-15
Lessov, C N; Phillips, T J (1998) Duration of sensitization to the locomotor stimulant effects of ethanol in mice. Psychopharmacology (Berl) 135:374-82
Belknap, J K; Richards, S P; O'Toole, L A et al. (1997) Short-term selective breeding as a tool for QTL mapping: ethanol preference drinking in mice. Behav Genet 27:55-66
Phillips, T J; Wenger, C D; Dorow, J D (1997) Naltrexone effects on ethanol drinking acquisition and on established ethanol consumption in C57BL/6J mice. Alcohol Clin Exp Res 21:691-702
Finn, D A; Crabbe, J C (1997) Exploring alcohol withdrawal syndrome. Alcohol Health Res World 21:149-56

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