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Charles Chavkin, Ph.D.,

Lab Website
Course Websites
  phcol534  phcol562
Box 357280
HSC D425

Office: 206.543.4266
Lab: 206.616.4954
Fax: 206.685.3822







We study different aspects of opioid peptide functioning in the nervous system. Endogenous opioids are released during stress to regulate nociception (pain), emotional state (euphoria, dysphoria, depression), and craving for addictive drugs (cocaine, opiates). We are asking how these complex behavioral effects are encoded by molecular, cellular and systems level events. At the molecular level, we study signal transduction events following opioid receptor activation using protein phosphorylation assays, specific antagonists and agonists, and transgenic mice having specific gene deletions and over-expressions. At the cellular level, we use confocal microscopy and electrophysiological assays to define the mechanisms of opioid effects on excitability. At the systems level, we use immunohistochemical analysis of changes in regional morphology, gene expression and protein phosphorylation to define the responsive neural circuits. At the behavioral level, we measure changes caused by opioid peptide release that mediate the stress response and potentiate the addictive properties of cocaine and opiates.

An example of the kind of results recently obtained include studies showing that chronic stress (repeated forced swim, repeated social defeat, chronic neuropathic pain, acute footshock) induces the release of endogenous dynorphin opioids that activate kappa opioid receptors and MAPK pathways which potentiate rewarding effects of cocaine and that induce relapse of drug seeking behavior. We are defining the sites in the brain where these effects occur, the intracellular signaling mechanisms responsible, and the electrophysiological effects in the local neuronal circuit underlying the behavioral responses. Our simple hypothesis is that dynorphin encodes the dysphoric effects of stressful experience that increase the motivation for euphoric/addictive drugs. Understanding the molecular and cellular mechanisms of these actions has therapeutic implications for the treatment of addiction.


Recent Publications 

Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system. - ABSTRACT

Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes. - ABSTRACT

Sciatic nerve ligation-induced proliferation of spinal cord astrocytes is mediated by kappa opioid activation of p38 mitogen-activated protein kinase. - ABSTRACT

Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating C-jun N-terminal kinase. - ABSTRACT

View all recent publications