Cocaine increases Ras-guanine nucleotide-releasing factor 1 protein expression in the rat striatum in vivo.
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.
Zhang
Guo-Chi
GC
Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA.
Hoffmann
Jason
J
Parelkar
Nikhil K
NK
Liu
Xian-Yu
XY
Mao
Li-Min
LM
Fibuch
Eugene E
EE
Wang
John Q
JQ
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020663:ras Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D020666:ras-GRF1 / Q000378:metabolism*
D018765:Dopamine Uptake Inhibitors; C525926:Rasgrf1 protein, rat; C504492:Rasgrf2 protein, rat; D020663:ras Guanine Nucleotide Exchange Factors; D020666:ras-GRF1; D003042:Cocaine