Characterization & Cloning of the Response Psychostimulant Mutant Gridlock'd

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DESCRIPTION (provided by candidate): The number of genes that mediate the process of addiction is large numbering possibly in the hundreds. One of the purposes of research into addiction is to find novel components that mediate addiction and which may be targeted for therapy. We have taken an unbiased classical genetic approach to find genes that control one aspect of addiction, sensitization to the drug. Using forward genetic screen we have isolated several mutants that are hyper or hypo-sensitive to cocaine in a locomotor response assay. One of these mutants, Gridlock'd, has low response to cocaine and amphetamine. We have mapped the mutation to chromosome 8. I propose to fine map this mutation on chromosome 8 (Objective 1), clone the mutation (Objective2) and behaviorally characterize the mutation (Objective 3). The cloning of Gridlock'd could reveal a new component of the incentive motivational reward pathway that leads to addiction. The knowledge of this new component could lead to therapies designed to target this pathway.