CONDITIONAL COUPLING OF STRIATAL DOPAMINE D1 RECEPTOR TO TRANSCRIPTION FACTORS - ONTOGENIC AND REGIONAL DIFFERENCES IN CREB ACTIVATION

The coupling of striatal dopamine D1 receptors to c-fos transcription exhibit all-or-none regional and ontogenic differences: the D1 agonist SKF 38393 fails to induce c-fos expression in the striatum, except du ring the early postnatal period in the striosomes, or in the caudal ex tremity of the striatum in adult animals. In an attempt to better deli neate the mechanism responsible for interrupting or enabling this cond itional coupling of D1 receptors to c-Sos transcription we have examin ed, through immunocytochemistry and gel shift assay, the activation of the cyclic AMP-response element binding protein (CREB) transcription factor in response to the D1 agonist in the murine striatum. Phosphory lated-CREB (P-CREB) immunoreactivity in response to the dopamine D1 ag onist (+/-)SKF 38393 (15 mg/kg, i.p.) was prominent in the caudal extr emity of the striatum in adult animals (P90). In neonatal (P5) mice, P -CREB immunoreactive neurons were observed both in the caudal and in t he rostral parts of the striatum, without obvious patchy distribution. Gel shift assays performed on nuclear protein extracts from either th e rostral or the caudal part of striatal tissue of neonatal (P5) or ad ult (P90) mice provided quantitative assessment, showing differences b oth in the amplitude and in the time course of the response, since P-C REB binding in adults culminated 45 min after (+/-)SKF 38393 (15 mg/kg , i.p.) injection, whereas the peak value appeared as soon as 10 min a fter injection in P5 mouse pups, suggesting the involvement of partly distinct transduction pathways. (C) 1998 Elsevier Science B.V. All rig hts reserved.