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Drug addiction is a serious mental illness involving severe motivational disturbances and loss of behavioral control leading to personal devastation. The disease afflicts millions of people with enormous social and economic costs to society. The Self Laboratory investigates the underlying neurobiological cause of drug addiction by first identifying neurobiological changes in the brain that develop as a consequence of chronic drug self-administration using rodent models. The role of these changes in key behavioral features of addiction, such as marked escalation in drug consumption and profound increases in drug craving, are determined by integrating modern pharmacological and molecular genetic approaches in animals with complex behavioral measures of motivation. The goal of our research is to better understand the biological basis of the disease and to identify major biological targets for potential therapeutic intervention to promote abstinence.