title: Cocaine increases Ras-guanine nucleotide-releasing factor 1 protein expression in the rat striatum in vivo.
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.
authors.affiliation: Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA.
authors.forename: Guo-Chi
authors.initials: GC
authors.lastname: Zhang
authors.forename: Jason
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Nikhil K
authors.initials: NK
authors.lastname: Parelkar
authors.forename: Xian-Yu
authors.initials: XY
authors.lastname: Liu
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Mao
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Fibuch
authors.forename: John Q
authors.initials: JQ
authors.lastname: Wang
mesh_terms: 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*
chemical_list: D018765:Dopamine Uptake Inhibitors; C525926:Rasgrf1 protein, rat; C504492:Rasgrf2 protein, rat; D020663:ras Guanine Nucleotide Exchange Factors; D020666:ras-GRF1; D003042:Cocaine