Jose Moron-Concepcion, Ph.D.
Assistant Professor
Affiliations: Scientist, Center for Addiction Research
Phone: 409-772-9641 Fax: 409-772-9642 Email: jomoronc@utmb.eduResearch Interests
Morphine dependence leads to relatively stable changes in gene expression, producing changes in neurotransmission and even in the structure of target neurons. Although opiate addiction has been studied for many years, the molecular mechanisms and pathways underlying this behavior are still poorly understood. Administration of morphine leads to the activation of μ-opioid receptors, inhibition of adenylyl cyclase by the activation of Gα i/o and activation of Gγβ-dependent cascades at the postsynaptic level. Recent studies using proteomics have identified ~200 postsynaptic proteins, among them proteins involved in the modulation and maintenance of synaptic structure, trafficking and signal transduction. Some of these proteins are thought to play a role in morphine-mediated complex behaviors, such as tolerance and dependence. Using a combination of classical biochemical techniques with a modern proteomic approach we observed a number of differences in the protein expression profile in the brain of animals that acquired morphine-dependent memory. Furthermore, quantitative mass spectrometry analysis showed that repeated morphine administration induced changes in the expression of selective proteins located in the postsynaptic fraction. These studies show that proteomics can serve as a valuable tool to globally explore proteins underlying the mechanisms of morphine addiction. Understanding the molecular basis of addiction will be extremely useful for developing novel pharmacologic tools for the treatment of drug addiction.
Selected Publications
J.A. Morón and L.A. Devi. “Use of proteomics for the identification of novel drug targets in brain diseases”. J Neurochem. In press.
J.A. Morón, Abul-Husn NS, Rozenfeld R, Dolios G, Wang R, Devi LA. “Morphine administration alters the profile of hippocampal postsynaptic density-associated proteins: A proteomic study focusing on endocytic proteins”. Mol Cell Proteomics (2007) 6: 29-42.
V. Chefer, T. Czyzyk, E. Bolan, J. Morón, J. Pintar, T. Shippenberg. “Endogenous kappa opioid receptor systems regulate mesoaccumbal dopamine dynamics and vulnerability to cocaine”. Journal of Neuroscience (2005) 25: 5029-5037.
B. Garcia, Y. Wei, J.A. Morón, R. Lin, J.A. Javitch, A. Galli. “AKT is essential for insulin modulation of amphetamine-induced human dopamine transporter cell surface redistribution”. Molecular Pharmacology (2005) 68: 102-109.
J.A. Morón, I. Zakharova, J. Ferrer, G. Mirrel, B. Hope, E. Lafer, Z. Lin, J. Wang, J. Javitch, A. Galli and T. Shippenberg. “Mitogen-Activated Protein Kinase regulates dopamine transporter surface expression and dopamine transport capacity”. Journal of Neuroscience (2003) 23: 8480-8488.
J.A. Morón, A. Brockington, R. Wise, B. Rocha and B. Hope. “ Dopamine uptake through the NET in brain regions with low levels of the DAT: Evidence from knockout mouse lines”. Journal of Neuroscience (2002) 22(2):389-395
J.A. Morón, L. Carvelli, K. Kahlig, J. Ferrer, N. Sen, J. Lechleiter, L. Leeb-Lundberg, G. Merril, E. Lafer, L. Ballou, T. Shippenberg, J. Javitch, R. Lin and A. Galli. “PI 3-kinase regulation of dopamine uptake”. Journal of Neurochemistry (2002) 81: 859-869.
L. Daws, P. Callaghan, J.A. Morón, K. Kahlig, T. Shippenberg, J. Javitch and A. Galli. “Cocaine increases dopamine uptake and cell surface expression of dopamine transporters”. Biochemical and Biophysical Research Communications (2002) 290: 1545-1550.
V. Chefer, J.A. Morón, B. Hope, W. Rea and T. S. Shippenberg. “Kappa opioid receptor activation prevents alterations in mesocortical dopamine neurotransmission that occur during abstinence from cocaine”. Neuroscience (2000) 101(3):619-627.