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Jose A. Moron-Concepcion"Proteomic analysis of morphine effects on hippocampal postsynaptic proteins"

Abstract :


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

Chefer VI, Czyzyk T, Bolan EA, Moron-Concepcion JA, Pintar JE, Shippenberg TS.
Endogenous kappa-opioid receptor systems regulate mesoaccumbal dopamine dynamics and vulnerability to cocaine.
J Neurosci 2005 May 18; 25(20):5029-37.

Garcia BG, Wei Y, Moron-Concepcion JA, Lin RZ, Javitch JA, Galli A.
Akt is essential for insulin modulation of amphetamine-induced human dopamine transporter cell-surface redistribution.
Mol Pharmacol 2005 Jul; 68(1):102-9.

Antoine de Daruvar