DOPAMINERGIC CONTROL OF GENE-TRANSCRIPTION DURING STRIATAL ONTOGENY -C-FOS INDUCTION BY D1 RECEPTOR ACTIVATION IN THE DEVELOPING STRIOSOMES

During striatal development, dopamine afferents initially reach the st riosomal compartment, and this early dopamine innervation is thought t o influence, through the D1 receptors first expressed in the developin g patches, the phenotype of target striatal cells. Dopaminergic contro l of gene expression during ontogeny could be mediated by transcriptio n factors such as c-fos, whose expression is regulated by synaptic sig nals. However, in the striatum of intact adult animals, D1 dopamine ag onists fail to induce c-fos expression. The c-fos response to D1 recep tor activation in adults requires a previous sensitization of dopamine rgic receptors by chronic treatment with reserpine or by lesion of the nigro-striatal pathway. In this work, we investigated through in situ hybridization the ability of striatal cells to express c-fos messenge r RNA (mRNA) in response to the D1 agonist SKF 38393 (4 to 8 mg/kg) in developing mice. During a transient postnatal period, c-fos expressio n in a patchy distribution was induced by D1 receptor activation: only a faint response was detected on postnatal day 1, but islands of stro ng hybridization signals for c-fos mRNA in response to the D1 agonist were observed at postnatal day 3, with a progressive decrease in inten sity from day 6 to day 15. The distribution of this transient c-fos re sponse corresponded to the early striosomal compartment since it match ed with the regions of intense mu-opioid and dopamine-D1 receptor bind ing, as assessed by autoradiography performed on adjacent sections. By day 21, as in adult animals, no more c-fos response to D1 agonists wa s observed, except in the most caudal division of the striatum. Strong expression, which persisted into adulthood, was detected in this regi on from the third postnatal day. This induction of striatal c-fos expr ession by D1 agonists during early postnatal development is indicative of an enhanced sensitivity of D1 receptors or of D1-associated transd uction pathways compared to the adult pattern, and suggests a possible role for dopamine-controlled c-fos gene expression in the development of target striatal neurons during this critical period.