This project aims to identify molecular changes that accompany chronic self-administration of cocaine. The specific aim is to use proteomic procedures to identify and quantify protein changes that might underlie the use and abuse of cocaine in reward relevant sites of the brain. The primary objective is to identify novel targets for therapeutic drug development. To this end, tissue from the brains of rats that have self-administered cocaine will be analyzed using quantitative two-dimensional electrophoresis and mass spectrometry to identify proteins whose expression or post-translational modification is altered during addiction. Regions of the brain that have been implicated in responses to cocaine will be examined. Attention will be given to synaptic plasma membrane proteins, including the dopamine transporter, that have putative roles in responses to cocaine. Approximately 1000-2000 proteins will be examined and the results will be analyzed to show addiction related change in regions of the brain that have been implicated in addictive behavior. The long term goal is to examine the potential of these proteins as novel targets for therapeutic interventions that may be used in treatment of addiction including relapse that is common in cocaine abusers.