George Koob, PhD

Dr. Koob's early research interests were directed at the neurobiology of emotion, with a focus on the theoretical constructs of reward and stress. He has made contributions to our understanding of the anatomical connections of the emotional systems and the neurochemistry of emotional function. Dr. Koob has identified afferent and efferent connections of the basal forebrain in the region of the nucleus accumbens, bed nucleus of the stria terminalis, and central nucleus of the amygdala in motor activation, reinforcement mechanisms, behavioral responses to stress, drug self-administration, and the neuroadaptation associated with drug dependence. Dr. Koob's work with the neurobiology of stress includes the characterization of behavioral functions in the central nervous system for catecholamines, opioid peptides, and corticotropin-releasing factor. Corticotropin-releasing factor, in addition to its classical hormonal functions in the hypothalamic-pituitary-adrenal axis, is also located in extrahypothalamic brain structures and may have an important role in brain emotional function. Recent use of specific corticotropin-releasing factor antagonists suggests that endogenous brain corticotropin-releasing factor may be involved in specific behavioral responses to stress, the psychopathology of anxiety and affective disorders, and drug addiction. Dr. Koob also has characterized functional roles for other stress-related neurotransmitters/neuroregulators such as norepinephrine, vasopressin, hypocretin (orexin), neuropeptide Y, and neuroactive steroids.

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.