The proposed research is to determine if stress (electrical, thermal) can modify communication involving opioid neuropeptides between the immune and nervous system. The study will attempt to monitor cellular conformational changes of invertebrate immunocytes and human leukocytes, by way of image analysis, for their responsiveness to opioid challenge. Additionally, high affinity opioid binding analysis will be performed on both cell populations to correlate binding efficacies with the conformational changes to determine opioid receptor subtype. This analysis will provide detailed knowledge that at present is lacking concerning this communication. Once this base line information is obtained, it will be analyzed for its significance in how Mytilus (Bivalvia) handle thermal and physical stress by way of the endogenous opioid-immune system. Previous work demonstrates that this opioid-immune-stress relationship in Mytilus is quite similar to that which is found in mammals. Lastly, """"""""stress-activated"""""""" cells will be transplanted into non-stressed animals to determine if this state of alertness can be transferred, indicating a chemical messenger (opioid). Both physiological and behavioral parameters (presynaptic dopamine release and ciliary activation) will be monitored to determine if the """"""""activated hemolymph and/or cells may modify ciliary regulation, thus, behavior. This bidirectional communication mechanism may partially account for cognitive and noncognitive influences on behavior. To date, little work has been performed on the cellular and molecular level in determining the mechanisms whereby stress can modify the functioning of these systems and in turn behavior. Indeed, if stress can modify immune function which is then transmitted to the CNS we may be developing a model of some mental disorders based on the sensing ability of the immune system. Furthermore, the detailed analysis of the opioid effects on the immune system has biomedical significance in the treatment of substance abuse since the sensing as well as the immune system may be compromised. The study will utilize undergraduate minority students as research assistants.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Resource-Related Research Projects (R24)
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Special Emphasis Panel (ZDA1 (17))
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Thadani, Pushpa
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College at Old Westbury
Schools of Arts and Sciences
Old Westbury
United States
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Fricchione, Gregory; Zhu, Wei; Cadet, Patrick et al. (2008) Identification of endogenous morphine and a mu3-like opiate alkaloid receptor in human brain tissue taken from a patient with intractable complex partial epilepsy. Med Sci Monit 14:CS45-49
Stefano, George B; Kream, Richard M; Mantione, Kirk J et al. (2008) Endogenous morphine/nitric oxide-coupled regulation of cellular physiology and gene expression: implications for cancer biology. Semin Cancer Biol 18:199-210
Stefano, George B; Kream, Richard M (2007) Endogenous morphine synthetic pathway preceded and gave rise to catecholamine synthesis in evolution (Review). Int J Mol Med 20:837-41
Cadet, Patrick; Mantione, Kirk J; Zhu, Wei et al. (2007) A functionally coupled mu3-like opiate receptor/nitric oxide regulatory pathway in human multi-lineage progenitor cells. J Immunol 179:5839-44
Cheng, Jeanette; Zhang, Chen; Han, Ji-Sheng et al. (2007) TENS stimulates constitutive nitric oxide release via opiate signaling in invertebrate neural tissues. Med Sci Monit 13:BR163-7
Stefano, George B; Bianchi, Enrica; Guarna, Massimo et al. (2007) Nicotine, alcohol and cocaine coupling to reward processes via endogenous morphine signaling: the dopamine-morphine hypothesis. Med Sci Monit 13:RA91-102
Esch, Tobias; Kim, Jae Won; Stefano, George B (2006) Neurobiological implications of eating healthy. Neuro Endocrinol Lett 27:21-33
Kream, Richard M; Stefano, George B (2006) De novo biosynthesis of morphine in animal cells: an evidence-based model. Med Sci Monit 12:RA207-19
Stefano, George B; Fricchione, Gregory L; Esch, Tobias (2006) Relaxation: molecular and physiological significance. Med Sci Monit 12:HY21-31
Zhu, Wei; Mantione, Kirk J; Casares, Federico M et al. (2006) Cholinergic regulation of endogenous morphine release from lobster nerve cord. Med Sci Monit 12:BR295-301

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