Acute amphetamine down-regulates RGS4 mRNA and protein expression in rat forebrain: distinct roles of D1 and D2 dopamine receptors.
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 alpha-subunit i- and/or q-coupled signaling pathways and favor mechanisms that counterbalance D(1) receptor stimulation.
Schwendt
Marek
M
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Gold
Stephen J
SJ
McGinty
Jacqueline F
JF
D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020710:RGS Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012457:Salicylamides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D001552:Benzazepines; D018492:Dopamine Antagonists; D020710:RGS Proteins; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C098799:RGS4 protein; D000661:Amphetamine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; C045989:eticlopride; D004298:Dopamine