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.

Future research plans

Future research is focused on understanding the neurobiological bases for altered motivational states associated with drug addiction at the neurocircuitry, cellular and molecular level and using these studies as a heuristic approach to the study of emotions. The ultimate goal is to understand how cellular and molecular changes produce changes in particular neurocircuits to convey negative emotional states that contribute to the motivation to seek drugs, but also contribute to other disorders of motivation in psychopathology. In addition, the laboratory will be exploring the relationship between pain and emotional systems in the context of the same neurocircuitry. The neurocircuitry under study involves specific elements of the basal forebrain involving the central nucleus of the amygdala, bed nucleus of the stria terminalis and elements of the ventral striatum including the shell and core of the nucleus accumbens. Neuropeptides of the brain stress systems outside of the hypothalamic-pituitary-adrenal system are hypothesized to have a key role in mediating changes in emotional state and include corticotropin releasing factor, dynorphin, vasopressin, substance P,  orexin and neuropeptide Y and nociceptin. Future studies will include identification of molecular factors that load such circuits and neurotransmitter system function, identification of cellular interactions between such brain stress systems and identification of the role of outputs such as the hypothalamus in expressing such negative emotional states. Such research will provide key information not only about the neurobiology of addiction, pain and stress but also key information about the neurobiology of motivational systems in general.