Generating Gene Knockout Mice for Studying Mechanisms Underlying Drug Addiction

Drug addiction is a chronic relapsing disease with psychological and social factors (1 ). Compulsive drug-taking is a central feature of drug addiction (2 –4 ). A major goal of drug abuse research is to understand the cellular and molecular mechanisms underlying the development of the loss of control over drug-taking (2 –4 ). Because the neurobiological mechanisms underlying the development of uncontrolled drug-taking behaviors are associated with the brain dopaminergic and glutamatergic systems (5 –8 ), animal models are obviously needed for the various investigations. With the development of the gene targeting approach (9 –13 ), genetically engineered mouse models have become increasingly useful for studying molecular mechanisms underlying drug addiction. Gene targeting allows a direct assessment of the contribution of individual genes to specific behaviors in mice. This technology provides a very useful alternative as opposed to pharmacological approach to dissect complex biological mechanisms, including how the dopamine (DA) receptors and the DA transporter function in vivo (14 –21 ).