The Animal Production Core (APC) will continue to supply selectively bred P/NP (alcohol-preferring and -nonpreferring) and HAD1-2/LAD1-2 (replicate high and low alcohol drinking) rats for research. For this competing renewal, the APC will also supply for the purpose of research selectively bred replicate HAP/LAP (high and low alcohol-preferring) and cHAP (crossed HAP produced by HAP1 x HAP2 cross) mice. These rodents will be provided to on-campus investigators supported by or affiliated with our Indiana ARC and other on-campus PIs who are funded by NIAAA with R01s, U01s, F31s, and our T32 Institutional Training Grant. The P and HAD1-2 rats are excellent animal models of the human disorder, alcoholism. The P/NP rats, and to a lesser degree, the HAD/LAD and HAP/LAP replicate lines of rodents have been extensively characterized from behavioral, neurochemical, neuropharmacological, and QTL perspectives. The P rats also constitute an excellent model to study """"""""binge"""""""" drinking, the alcohol-deprivation effect (ADE, the equivalent of """"""""relapse"""""""" drinking or """"""""craving"""""""") and adolescent alcohol abuse. Furthermore, the P rat is an excellent animal model to better define the neurocircuitry of the reward action of ethanol and the relationship of CREB (cAMP-responsive-element binding) and neuropeptide Y gene expression to the anxiolytic effect of alcohol.
The Specific Aims are: 1) To continue to maintain our nucleus colonies of selectively bred P/NP rats. 2) To produce for on-campus researchers sufficient number of selectively bred P/NP and HAD1-2/LAD1-2 rats. 3) To continue to selectively breed the replicate HAP/LAP mouse lines and the cHAP mouse line and to produce sufficient animals for on-campus research. 4) To maintain a colony of N/Nih rats (the foundation stock for the selective breeding of the HAD/LAD and HAS/LAS replicate lines) because this heterogeneous stock is not kept at NIH and it is a relevant control line in studies that compare the HAD1-2 lines with their contrasting LAD1-2 lines. 5) To continue to assist in the creation of reciprocal congenic lines from inbred P/NP strains in order to further narrow the critical region of Chr 4 for alcohol preference in the QTL with a LOD score of 9.2. The success of the APC and our IARC will provide important advances in the understanding of the genetic determinants and neurocircuitry of alcoholism. These scientific advances in turn will pave the way for medication development to treat various aspects of alcoholism.
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