title: Amphetamine alters Ras-guanine nucleotide-releasing factor expression in the rat striatum in vivo.
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 2.5h after drug injection and returned to normal levels by 6h. 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, Missouri 64108, USA.
authors.forename: Nikhil K
authors.initials: NK
authors.lastname: Parelkar
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Chu
authors.forename: Ming-Lei
authors.initials: ML
authors.lastname: Guo
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Mao
authors.forename: John Q
authors.initials: JQ
authors.lastname: Wang
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D020663:ras Guanine Nucleotide Exchange Factors / Q000378:metabolism; D020666:ras-GRF1 / Q000378:metabolism*
chemical_list: C504492:Rasgrf2 protein, rat; D020663:ras Guanine Nucleotide Exchange Factors; D020666:ras-GRF1; D000661:Amphetamine; D004298:Dopamine
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