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

Abstract

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 D 1 receptor antagonist SCH‐23390 but not by specific D 2 receptor antagonists. Apomorphine, a dopamine agonist that acts at both D 1 and D 2 receptors, and SKF‐38393, a specific D 1 receptor agonist, produce similar mRNA changes in rats pretreated with either 6‐hydroxydopamine or reserpine, whereas LY‐171,555, a specific D 2 receptor agonist, has no effect. Direct dopamine agonist effects on these immediate early gene mRNA levels are also blocked by D 1 but not by D 2 antagonists. We observed similar, although less robust, changes in c‐fos and fos‐B mRNA levels. These results demonstrate that striatal D 1 dopamine receptors are coupled to activation of multiple transcription factor genes, including zif268 and jun‐B as well as members of the fos family.