Rats and mice as models for human disease have made invaluable contributions to almost every field of human medicine - alcoholism included. Recently, scientists have published nearly the entire genome of the common rat, making it possible to compare it to the genetic maps of mice and humans, and to improve the efficiency of candidate gene identification. This major advance is expected to yield important clues into the genetics and neurobiology of alcohol abuse and alcoholism. We have raised by selective breeding the P/NP and HAD/LAD (replicate) rat lines and the HAP/LAP (replicate) mouse lines that exhibit divergent alcohol preference. We have also raised inbred strains of P/NP, HAD1/LAD1 and HAD2/LAD2 which will be useful for performing genetic crosses and intercrosses. These selected rat and mouse lines and inbreeds constitute a unique, already established, research resource. The P rats fulfill all of the criteria of an animal model of alcoholism. By contrast, due to incomplete characterization, the HAD rats and the HAP mice at this time only satisfy some of the criteria. The P and HAD rats are also excellent animal models to study alcohol relapse or craving (they display the alcohol deprivation effect, ADE), to study adolescent alcohol abuse, and for medicinal development in the treatment of alcoholism. The overall goal of this application is to establish an Alcohol Research Resource Center so that these selectively bred and inbred lines/strains can be widely shared by alcohol researchers at both Indiana University and with many off-campus investigators in external research and academic institutions. The budgetary charge for these rats will be reduced from the current charge structure established by our Indiana Alcohol Research Center.
The specific aims of this application includes: (1) to continue selective breeding of the replicate HAD/LAD lines of rats. (2) To produce and export to off-campus researchers selectively bred or inbred P/NP, HAD1/LAD1 and HAD2/LAD2 rats. And (3) to produce and export to external institutions selectively bred HAP1/LAP1 and HAP2/LAP2 mice.
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