By Gerald E. McClearn (auth.), John C. Crabbe Jr., R. Adron Harris (eds.)

HISTORICAL heritage using genetic animal types in neuroscience and biomedical examine is exhibiting dramatic development. The earliest software of those versions to analyze on drug mechanisms used to be within the quarter of alcohol examine. Mardones (1951) stated profitable selective breeding of rats who prefer and never who prefer to drink alcohol less than quite a few stipulations of nutritional deficiency, suggesting genetic keep an eye on of alcohol ingesting. McClearn and Rodgers (1959, 1961) defined alterations between inbred mouse lines in choice for 10Ofo ethanol ideas as opposed to faucet water. energetic exploration of this phenomenon endured till the early Seventies, ultimately spawning the complete diversity of alcohol genetic study reviewed in Chapters 2 and three of this quantity. significantly, oral alcohol self-administration has served because the foundation for the advance of numerous rat traces bred for choice or aversion, and those traces are very actively being investigated. The pioneering learn of Dr. McClearn and others used to be very large­ ranging in its conceptual scope and a minimum of touched on all matters presently lower than severe research. the elemental strategy used to be to spot low and high preferrers between inbred lines of mice and to look for choice correlates in different features. One significant thrust of early learn was once to aim to give an explanation for pressure variations in choice as a functionality of underlying alterations in styles of caloric usage. experiences of those reviews concluded that dietary components couldn't thoroughly clarify choice ameliorations (Rod­ gers, 1966; McClearn, 1968).

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1984) estimated low but significant heritabilities for most of the tests used to measure physical dependence. No maternal effects were detected, but there was a sexby-genotype interaction not attributable to sex linkage. , 1982) may not have taken full advantage of the available additive genetic variance in female mice, although it did in male mice (Corley and Allen, 1988). , 1983b). However, as the authors indicated, withdrawal severity assessments differed widely. , 1989a, for review) has led to its discontinuation, suggesting that this composite selection index, or perhaps use of the oral route to produce alcohol dependence, may not be the most appropriate means of obtaining a good animal model for assessing ethanol dependence.

219-233. Weir, B. , Eisen, E. , Goodman, M. , and Namkoong, G. ), 1988, Proceedings of the Second International Conference on Quantitative Genetics, Sinauer Associates, Sunderland, MA. Wilson, J. , Erwin, V. , DeFries, J. , Petersen, D. , 1984, Ethanol dependence in mice: Direct and correlated responses to ten generations of selective breeding, Behav. Genet. 14:235-256. 2 Behavioral Studies of Genetic Differences in Alcohol Action TAMARA J. PHILLIPS AND JOHN C. CRABBE, JR. Many investigations of alcohol (ethanol) sensitivity have addressed the question of genetic determination using genetically defined animal populations, particularly mouse and rat stocks.

By use of interval mapping, these investigators 19 THE TOOLS OF PHARMACOGENETICS generated QTL (quantitative trait loci) likelihood maps for loci affecting three quantitative traits: fruit mass, soluble solids concentration, and pH. The QTLs were found for fruit mass on six of the 12 chromosomes, for soluble solids concentration on four, and for pH on five. These QTLs "account for" 58, 44, and 400/0, respectively, of the phenotypic variance. , in press). Consider Fig. 7, which rearranges the distribution of Fig.

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