Amphetamine alters Ras-guanine nucleotide-releasing factor expression in the rat striatum in vivo

Nikhil K. Parelkar, Qian Jiang, Xiang Ping Chu, Ming Lei Guo, Li Min Mao, John Q. Wang

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Ras-guanine nucleotide-releasing factors (Ras-GRFs) are densely expressed in neurons of the mammalian brain. As a Ras-specific activator predominantly concentrated at synaptic sites, Ras-GRFs activate the Ras-mitogen-activated protein kinase (Ras-MAPK) cascade in response to changing synaptic inputs, thereby modifying a variety of cellular and synaptic activities. While the Ras-MAPK cascade in the limbic reward circuit is well-known to be sensitive to dopamine inputs, the sensitivity of its upstream activator (Ras-GRFs) to dopamine remains to be investigated. In this study, the response of Ras-GRFs in their protein expression to dopamine stimulation was evaluated in the rat striatum in vivo. A single systemic injection of the psychostimulant amphetamine produced 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. The reliable increase was seen 2.5 h after drug injection and returned to normal levels by 6 h. In contrast to Ras-GRF1, protein levels of Ras-GRF2 in the striatum were not altered by amphetamine. In addition to the striatum, the medial prefrontal cortex is another forebrain site where amphetamine induced a parallel increase in Ras-GRF1 but not Ras-GRF2. No significant change in Ras-GRF1/2 proteins was observed in the hippocampus. These data demonstrate that Ras-GRF1 is a susceptible and selective target of amphetamine in striatal and cortical neurons. Its protein expression is subject to the modulation by acute exposure of amphetamine.

Original languageEnglish (US)
Pages (from-to)50-56
Number of pages7
JournalEuropean Journal of Pharmacology
Volume619
Issue number1-3
DOIs
StatePublished - Oct 1 2009

Keywords

  • ERK (extracellular signal-regulated kinase)
  • GEF (guanine nucleotide exchange factor)
  • GRF (guanine nucleotide-releasing factor)
  • Hippocampus
  • Medial prefrontal cortex
  • Nucleus accumbens

ASJC Scopus subject areas

  • Pharmacology

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