Activation of c-Jun N-terminal kinase is required for the regulation of endoplasmic reticulum stress response in the rat dorsal striatum following repeated cocaine administration

Neuropharmacology. 2010 Jul-Aug;59(1-2):100-6. doi: 10.1016/j.neuropharm.2010.04.009. Epub 2010 Apr 22.

Abstract

Repeated exposure to cocaine upregulates endoplasmic reticulum (ER) stress response and c-Jun N-terminal kinase (JNK) phosphorylation is associated with the ER stress response in neurons. In this study, we investigated the involvement of JNK in the regulation of the ER stress response following repeated cocaine administration in the dorsal striatum in vivo. The results showed that systemic injections of cocaine (20 mg/kg) for seven consecutive days increased the induction of p46 JNK (JNK) phosphorylation, immunoglobulin heavy chain binding protein (BiP), the ER stress-associated protein caspase-12, and behavioral locomotor activity. This enhancement of BiP and caspase-12 expression and locomotor response was reduced by inhibiting JNK. Similar reduction of elevated JNK phosphorylation was induced by blocking dopamine D1 receptors, N-methyl-D-aspartate (NMDA) receptors, and group I metabotropic glutamate receptors (mGluRs). These data suggest that JNK activation following repeated cocaine administration is required for the regulation of the ER stress protein expression and behavioral alteration in the dorsal striatum. Stimulation of dopamine D1 receptors, NMDA receptors or group I mGluRs participates in the regulation of JNK activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 12 / metabolism
  • Cocaine / toxicity*
  • Corpus Striatum / drug effects*
  • Corpus Striatum / enzymology
  • Corpus Striatum / physiopathology
  • Dopamine Uptake Inhibitors / toxicity*
  • Endoplasmic Reticulum / drug effects*
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / physiology
  • Endoplasmic Reticulum Chaperone BiP
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Heat-Shock Proteins / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Male
  • Motor Activity / drug effects
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / physiology
  • Phosphorylation / drug effects
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Stress, Physiological / drug effects*
  • Stress, Physiological / physiology

Substances

  • Dopamine Uptake Inhibitors
  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins
  • Receptors, Dopamine D1
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • metabotropic glutamate receptor type 1
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Casp12 protein, mouse
  • Caspase 12
  • Cocaine