Department of Pharmacology Faculty
Burt M. Sharp, M.D.
Van Vleet Professor
Room 115 Crowe Research Building
- 1971 B.A. State University of New York-Stony Brook
- 1975 M.D. University of Cincinnati, College of Medicine
My research program has dual foci involving (1) the basic neurochemistry and molecular neurobiology of nicotine and (2) cellular and biochemical approaches to understand the action of opioid peptides on the immune system.
The nicotine research uses in vivo microdialysis coupled with measurements of biogenic amines and excitatory amino acids to understand both the neurochemical basis for addiction to nicotine and the beneficial therapeutic effects of nicotinic agonists on hypothalamic and hippocampal function. In many of these studies, nicotine is delivered acutely through intra-jugular catheters and cannulae that are chronically implanted in specific CNS sites. Animals also learn to self-administer nicotine through operant conditioning that mimics human smoking. In vivo microdialysis in these self-administering animals permits analysis of changes in brain neurochemistry and direct correlation of these with drug-dependent behavior. Using RT-PCR, analyses are made of specific gene expression in micropunched areas of brain. Similarly, in situ hybridization analyses are used to characterize the effects of nicotine self-administration on short and longterm changes in CNS gene expression.
My research on opioid immunobiology seeks to understand the cellular and molecular basis for the modulatory effects of opiates and opioid peptides on lymphocytes, specifically T-cells. Using fluorescence flow cytometry and RT-PCR, we are characterizing the expression of delta opioid receptors on specific subsets of T lymphocytes. Biochemical and immunological approaches (e.g.immunoprecipitation, Western immunoblotting, receptor binding) are used to elucidate the signal transduction pathways that mediate the anti-proliferative actions of delta opioid receptors on T-cells. Our current focus is on the role of mitogen-activated protein kinases (MAPKs) in opioid signaling, as this pertains to the effects of opioids on MAPK-dependent interleukin-2 production.