Dr. Koob also is one of the world’s authorities on the neurobiology of drug addiction. He has contributed to our understanding of the neurocircuitry associated with the acute reinforcing effects of drugs of abuse and more recently on the neuroadaptations of these reward circuits associated with the transition to dependence. He has validated key animal models for dependence associated with drugs of abuse and has begun to explore a key role of anti-reward systems in the development of dependence. The identification of specific neurochemical systems within the basal forebrain system of the extended amygdala involved in motivation has significant theoretical and heuristic impact. From a theoretical perspective, identification of a role for dopaminergic, opioidergic, GABAergic, glutamatergic and corticotropin-releasing factor systems in the excessive drug taking provides a neuropharmacologic basis for the allostatic changes hypothesized to drive the process of pathology associated with addiction, anxiety, and depression. From a heuristic perspective, these findings provide a framework for further molecular, cellular and neurocircuit research that will identify the basis for individual differences in vulnerability to pathology.