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Acute amphetamine down‐regulates RGS4 mRNA and protein expression in rat forebrain: distinct roles of D 1 and D 2 dopamine receptors
Author(s) -
Schwendt Marek,
Gold Stephen J.,
McGinty Jacqueline F.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03669.x
Subject(s) - forebrain , amphetamine , dopamine , receptor , dopamine receptor , messenger rna , neuroscience , biology , dopamine receptor d1 , endocrinology , microbiology and biotechnology , medicine , central nervous system , gene , biochemistry
Administration of psychostimulants modulates mRNA of several regulators of guanine nucleotide‐binding protein signaling (RGSs) proteins in the brain. In the present study, the regulation of amphetamine‐induced decrease of RGS4 expression in the rat forebrain was evaluated. RGS4 mRNA was reduced by amphetamine in an inverse, dose‐dependent manner. The lowest dose (2.5 mg/kg) decreased RGS4 mRNA in caudate putamen for up to 6 h after injection whereas the decrease in several frontal cortical areas was detected at 3 h only. Analysis of RGS4 immunoreactivity by western blotting revealed a decrease 3 h after amphetamine solely in the caudate putamen. Systemic administration of D 1 (SCH23390) or D 2 (eticlopride) receptor antagonists blocked amphetamine‐induced locomotion but amphetamine augmented both the SCH23390‐induced increase and the eticlopride‐induced decrease in RGS4 mRNA in the caudate putamen. Further, the down‐regulation of RGS4 immunoreactivity by eticlopride was robust whereas the effect of SCH23390 was blunted as compared with its effect on mRNA. These data suggest that, by decreasing RGS4 expression in the caudate putamen via D 1 receptors, acute amphetamine could disinhibit RGS4‐sensitive guanine nucleotide‐binding protein α‐subunit i‐ and/or q‐coupled signaling pathways and favor mechanisms that counterbalance D 1 receptor stimulation.