Cocaine increases Ras-guanine nucleotide-releasing factor 1 protein expression in the rat striatum in vivo

  • Zhang G
  • Hoffmann J
  • Parelkar N
 et al. 
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Abstract

Psychostimulants activate the Ras-mitogen-activated protein kinase (Ras-MAPK) cascade in the limbic reward circuit and thereby trigger a transcription-dependent mechanism underlying enduring synaptic plasticity related to addictive properties of drugs of abuse. The Ras-specific activator, Ras-guanine nucleotide-releasing factor (Ras-GRF), is predominantly expressed at synapses and is thought to actively regulate Ras-MAPK responses to changing synaptic signals. In this study, a possible influence of cocaine on Ras-GRF gene expression at the protein level in the rat striatum was investigated in vivo. A single systemic injection of cocaine induced an increase in Ras-GRF1 protein levels in both the dorsal (caudoputamen) and ventral (nucleus accumbens) striatum. The increase in Ras-GRF1 proteins was dose-dependent and was a delayed and transient event. In contrast to Ras-GRF1, a closely related Ras-GRF2 showed no change in its protein abundance following cocaine administration. These data identify the Ras activator, Ras-GRF1, although not Ras-GRF2, as a susceptible target to cocaine stimulation in striatal neurons. © 2007 Elsevier Ireland Ltd. All rights reserved.

Author-supplied keywords

  • CDC25
  • Caudate
  • ERK
  • GEF
  • MAPK
  • Nucleus accumbens
  • Ras-GRF2
  • Stimulant

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Authors

  • Guo Chi Zhang

  • Jason Hoffmann

  • Nikhil K. Parelkar

  • Xian Yu Liu

  • Li Min Mao

  • Eugene E. Fibuch

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