The focus of this review is primarily on recent developments in bidirectional translational research on the addictions, within the Laboratory of the Biology of Addictive Diseases at The Rockefeller University. This review is subdivided into major interacting aspects, including: a) Investigation of neurobiological and molecular adaptations (e.g., in genes for the opioid receptors or endogenous neuropeptides) in response to cocaine or opiates, administered under laboratory conditions modeling chronic patterns of human self-exposure (e.g., chronic escalating "binge"). b) The impact of such drug exposure on the hypothalamic-pituitary-adrenal (HPA) axis and interacting neuropeptidergic systems (e.g., opioid, orexin and vasopressin). c) Molecular genetic association studies using candidate gene and whole genome approaches, to define particular systems involved in vulnerability to develop specific addictions, and response to pharmacotherapy. d) Neuroendocrine challenge studies in normal volunteers and current addictive disease patients along with former addicts in treatment, to investigate differential pharmacodynamics and responsiveness of molecular targets, in particular those also investigated in the experimental and molecular genetic approaches described above.
KeywordsCocaine; heroin; methadone; opioid; dynorphin; beta-endorphin; addiction; mu-opioid; kappaopioid; molecular genetics; HPA axis As the Laboratory of the Biology of Addictive Diseases at The Rockefeller University, and as an NIH-NIDA P60 Research Center, we are honored and delighted to join in the celebration of the 35 th Anniversary of NIDA. Our report herein will focus on some accomplishments of our scientists over the last five years, since we were privileged also to write a scientific tribute to the 30th Anniversary of NIDA . Selected topics only will be covered herein, primarily ones of interest both from the standpoint of basic science findings, with potential implications not only for the addictive diseases, but also for the molecular neurobiological mechanisms underlying many other human disorders, including Parkinsonism, Alzheimer's and Huntington's disease, as well as many which further elucidate normal physiology. In addition, our studies, of course, have significant implications for specific addictive diseases.