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Current Research Projects MIDARP (funded by NIDA) The Minority Institutions' Drug Abuse Research Development Program (MIDARP)
at the Neuroscience Research Institute is focused on studies in the areas of
substance abuse. Previously the Old Westbury MIDARP discovered a novel
opiate receptor subtype, designated mu3, that is opiate alkaloid selective and
opioid peptide insensitive. The faculty have special interests in molecular and
cellular neuroimmunology related to the National Institute on Drug Abuse
priorities, e.g., endogenous morphine and opiate induced immune downregulation.
The major research projects incorporated into this program are: 1) Determining
the process of morphine biosynthesis, including the identification of morphine
precursors and enzymes; and 2) Determining the signal transduction pathway, gene
and protein expression of the mu3 opiate receptor in various conditions and how
it is related to drug addiction, and to clone, sequence, and study the function
of the new mu4 gene. MRISP (funded by NIMH) The Minority Research Infrastructure Support Program (MRISP) at the Neuroscience Research Institute is focused on studies in the areas of neuroscience that are of importance to the understanding of its molecular processes, particularly in the fields of morphine neurobiology, aside from substance abuse issues, and the subfield of neuroimmunology, e.g., AIDS and opiate induced alteration of neural processes. The major research projects incorporated into this program are: 1) Effects of endogenous morphine on neural processes, not related to substance abuse phenomena; and 2) Interaction of parasitic opioid peptides in the modulation of host behavior. The first project is designed to study alterations in neural processes as a result of opiate exposure. It has documented the presence of endogenous morphine in neural tissues as well as cloned a novel opiate alkaloid selective and opioid peptide insensitive receptor designated μ3. The second project gains insight from studying the ability of parasites to escape immune surveillance by synthesizing opiate/opioid signaling molecules. The projects use alternative animal models (i.e., invertebrate neural tissues), reducing animal care-costs and paying attention to concerns raised over the use of animals in research. This Program examines opiate processes that transcend pain and have the potential to influence an animal’s behavior. The OWNRI has previously made significant contributions to the understanding of how opiates and cannabinoid substances contribute to neural and immune processes. The Principal Investigator, Dr. George B. Stefano, the Co-Principal Investigator, Steve Pryor, and their students have conducted many NIMH related studies. Results from these studies demonstrate that: A) μ3 opioid receptors are present on human granulocytes and invertebrate immunocytes and it appears to be involved with chemotaxis; B) μ3 opiate receptor that is opiate alkaloid selective and opioid peptide insensitive is on human monocytes, granulocytes and endothelial cells as well as on invertebrate immunocytes, microglia and neural tissues; C) μ3 coupling to nitric oxide release in these same tissues leads to immunocyte down regulation, i.e., rounding, loss of adherence and inhibition of cytokine secretion; D) Anandamide receptors also are present on these tissues and are coupled to nitric oxide release; E) Invertebrates contain proenkephalin; F) Invertebrates contain prodynorphin; G) Invertebrates contain proopiomelanocortin; H) Invertebrates contain enkelytin that is part of the Unified Protective Neuroimmune Response; and I) Morphine regulation of neutral endopeptidase activity by coupling to nitric oxide. These studies have provided a new insight into the mechanisms of these substances formerly believed to have activities associated only with pain.
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