D₁ Dopamine Receptor Activation of Multiple Transcription Factor Genes in Rat Striatum

Abstract

Recent studies have shown that dopamine receptor agonists induce expression of Fos-like immunoreactivity in rat striatal neurons. The protooncogene c-fos belongs to a family of immediate early genes that are rapidly induced in fibroblasts by growth factors. In light of previous findings that several immediate early gene mRNAs that encode proven or putative transcription factors are differentially regulated by neuronal stimulation in vivo, we have examined the effect of dopaminergic agents on mRNA levels of several such genes using in situ hybridization and northern blot analysis. d-Amphetamine (2.5-10 mg/kg i.p.) causes a rapid but transient dose-dependent increase in zif268 and jun-B mRNA levels in striatum that was abolished by striatal 6-hydroxydopamine lesions or by pretreatment with the specific D1 receptor antagonist SCH-23390 but not by specific D2 receptor antagonists. Apomorphine, a dopamine agonist that acts at both D1 and D2 receptors, and SKF-38393, a specific D1 receptor agonist, produce similar mRNA changes in rats pretreated with either 6-hydroxydopamine or reserpine, whereas LY-171,555, a specific D2 receptor agonist, has no effect. Direct dopamine agonist effects on these immediate early gene mRNA levels are also blocked by D1 but not by D2 antagonists. We observed similar, although less robust, changes in c-fos and fos-B mRNA levels. These results demonstrate that striatal D1 dopamine receptors are coupled to activation of multiple transcription factor genes, including zif268 and jun-B as well as members of the fos family.

Motor-Skill Learning-Associated Gene Regulation in the Striatum: Effects of Cocaine

“…We did not determine which of these two pathways showed differential c-fos induction by the cocaine challenge after the running-wheel training. Psychostimulant-induced immediate-early gene expression is principally mediated by D1 receptors (Graybiel et al, 1990;Young et al, 1991;Cole et al, 1992;Steiner and Gerfen, 1995;Drago et al, 1996;Moratalla et al, 1996) in interaction with glutamate input (see Berke and Hyman, 2000). Moreover, double-labeling studies demonstrated that psychostimulants induce c-fos predominantly in direct Correlation coefficients (r) for correlations between increases in ambulation and c-fos (left) or substance P mRNA levels (right) in 26 striatal sectors are shown for rats that received a cocaine challenge (25 mg/kg) 24 h after the 1-, 2-or 8-day wheel training (RC/C and LC/C groups pooled).…”

Augmented D1 Dopamine Receptor Signaling and Immediate-Early Gene Induction in Adult Striatum After Prenatal Cocaine

“…Striatal dysfunction is implicated in a variety of neuropsychiatric disorders (37)(38)(39), including drug addiction (40,41). Genes induced in striatal neurons by systemic psychostimulant administration include c-fos (42,43), zif 268 (44) and homer 1a (45,46). Such gene induction is principally mediated by D 1 -like receptors; however, D 2 -like receptors additionally modulate such effects (47,48).…”

“…Such gene induction is principally mediated by D 1 -like receptors; however, D 2 -like receptors additionally modulate such effects (47,48). Notably, psychostimulantinduced gene regulation is abolished by D 1 receptor blockade (42,44,49,50), or by targeted deletion of D 1 receptors (51-54).…”

Striatal mRNA expression patterns underlying peak dose l-DOPA-induced dyskinesia in the 6-OHDA hemiparkinsonian rat

“…In L-DOPA treated animals (both dyskinetic and nondyskinetic) 42 genes were more highly expressed and 95 less highly expressed when compared with untreated parkinsonian controls (Figure 2 B and 2 C; total genes enclosed within both of the lowermost circles). A subset of genes was selected for further examination, based on their role as transcription factors and immediate early genes, known to be activated in response to dopamine receptor stimulation (Cole et al, 1992;Moratalla et al, 1992;Berke et al, 1998). Expression was examined in RNA from the individual rats in the RNA-seq experiment using RT-qPCR to verify patterns observed in the RNA-seq dataset and the results compared with the RNA-seq counts (Figure 3).…”

“…An adjusted p-value of 0.05 was used as the threshold for significance (Cameron et al, 2013). A subset of genes were selected for further examination, based on their role as transcription factors and genes known to be activated soon after dopamine receptor stimulation (Cole et al, 1992;Moratalla et al, 1992;Berke et al, 1998). These genes: Arc, Egr1, Fos, Junb, and Nr4a1, were examined using TaqMan gene expression probe sets (Life Technologies) to confirm gene expression patterns observed in the RNA-seq dataset.…”