The goal of this project is to study the function of four genes in rodent models of binge drinking and alcohol dependence. The genes include Lmo3 and Lmo4, which encode transcriptional regulators, Alk, which encodes a receptor tyrosine kinase, and Mdk, which encodes a ligand that regulates the Alk gene product. Preliminary work suggests that these four genes cooperate to regulate behaviors associated with excessive alcohol consumption. The work will provide basic insights into the role of a new signaling pathway in controlling behaviors that model human alcohol abuse. In addition, some of the genes in the pathway are protein kinases, which are regarded as excellent targets for drug development. This project will thus lay the groundwork for development of novel pharmacotherapies for alcohol abuse in humans.