Genetic variation and brain gene expression in rodent models of alcoholism implications for medication development.
Much research on experimental animals that is aimed to decipher genetic factors involved in alcoholism has been devoted to either models of innate alcohol-related phenotypes or responses after acute alcohol challenge. Such focus has, however, limitations when it comes to the pathogenetic mechanism underlying alcohol addiction, because the progression into the disorder takes years and genetic as well as environmental factors may exert different influences along this trajectory. Animal models of the neuroadaptations involved in the development of dependence exist, but have been difficult to implement for genetic and genomics analysis. Consequently, currently available data have been difficult to reconcile with the human condition and could be misleading in predicting targets for medication development. This review will illustrate strengths and pitfalls of genomic approaches in rodent models of alcoholism and emphasize the need for convergent lines of evidence to improve the predictive value of such studies. Examples of a convergent research approach include validation studies for Agt, Arrb2, Crhr1, Grin3a, and Npy.
Björk
Karl
K
Translational Neuropharmacology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Hansson
Anita C
AC
Sommer
Wolfgang H
WH
D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D012307:Risk Factors; D012377:Rodentia / Q000235:genetics