Use of genetic analyses to refine phenotypes related to alcohol tolerance and dependence

Various explanations for the dependence on alcohol are attributed to the de velopment of tolerance to some of alcohol's effects, alterations in sensiti vity to its rewarding effects, and unknown pathologic consequences of repea ted exposure. All these aspects of dependence have been modeled in laborato ry rodents, and these studies have consistently shown a significant influen ce of genetics. Genetic mapping studies have identified the genomic locatio n of the specific genes for some of these contributing phenotypes. In addit ion, studies have shown that some genes in mice seem to affect both alcohol self-administration and alcohol withdrawal severity: genetic predispositio n to high levels of drinking covaries fifth genetic predisposition to low w ithdrawal severity, and vice versa. Finally, the role of genetic background on which genes are expressed is important, as are the specifics of the env ironment in which genetically defined animals are tested. Understanding dep endence will require disentangling the multiple interactions of many contri buting phenotypes, and genetic analyses are proving very helpful. However, rigorous understanding of both gene-gene and gene-environment interactions will be required to interpret genetic experiments clearly.