The dopamine D1 receptor agonist, but not the D2 receptor agonist, induces gene expression of Homer 1a in rat striatum and nucleus accumbens.
Stimulation of dopamine receptors may induce striatal Homer 1a, an immediate-early gene (IEG) that is involved in the molecular mechanism for the signaling pathway of the group I metabotropic glutamate receptors. This study examined the effects of the agonists for dopamine D(1)-like and D(2)-like receptors on gene expression of Homer 1a, in comparison with the IEG c-fos expression, in the discrete brain regions of rats. The D(1)-like agonist SKF38393 (20 mg/kg, s.c.) significantly increased the mRNA levels of Homer 1a in the striatum and nucleus accumbens, but not in the medial prefrontal cortex or hippocampus, 2 h after injection, whereas the D(2)-like agonist quinpirole (1 mg/kg, s.c.) had no significant effect on Homer 1a mRNA levels in any brain region examined. Co-administration of SKF38393 and quinpirole significantly increased Homer 1a mRNA levels in the striatum, nucleus accumbens and hippocampus, while this effect was not significantly greater than that of SKF38393 alone. Any treatment did not affect the mRNA levels of other splicing variants, Homer 1b or 1c. In contrast, combination of both dopamine agonists produced a greater increase than SKF38393 did in the mRNA levels of c-fos in the nucleus accumbens, striatum and substantia nigra. These results suggest that stimulation of D(1)-like receptors, but not D(2)-like receptors, may induce gene expression of Homer 1a in the striatum and nucleus accumbens. However, in contrast to c-fos expression, it is unlikely that co-activation of both D(1)-like and D(2)-like receptors exerts a synergic action on Homer 1a expression in these regions.
Yamada
Hidetaka
H
Department of Neuropsychiatry, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
Kuroki
Toshihide
T
Nakahara
Tatsuo
T
Hashimoto
Kijiro
K
Tsutsumi
Tetsuyuki
T
Hirano
Makoto
M
Maeda
Hisao
H
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D000072233:Homer Scaffolding Proteins; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011913:Rats, Inbred BB; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002352:Carrier Proteins; D018491:Dopamine Agonists; D000072233:Homer Scaffolding Proteins; D020033:Protein Isoforms; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine