Development of striatal dopaminergic function. II: Dopaminergic regulation of transcription of the immediate early gene zif268 and of D1 (D1a) and D2 (D2a) receptors during pre- and postnatal development.

摘要

We investigated cocaine- and apomorphine-mediated induction of the zinc finger immediate early gene (IEG), zif268, during striatal ontogeny. Acute cocaine or apomorphine treatment increased striatal zif268 mRNA on embryonic day 20 (E20), postnatal day 5 (P5), and in adults, but not on E15, with developmentally distinct anatomical profiles. SCH23390 pretreatment completely attenuated zif268 gene expression at all ages, but eticlopride treatment of E20 and P5 rats prior to cocaine enhanced zif268 expression beyond that observed with cocaine alone. In adults, eticlopride pretreatment partially attenuated the cocaine-mediated increase in zif268 expression. E20 and P5 D2 receptors appear to be negatively coupled to zif268 expression; whereas the adult D2 receptor, like the D1 receptor, appears to stimulate zif268 expression. Acute cocaine increased D1 but not D2 receptor mRNA levels within 24 h but had no effect on D1 or D2 receptor binding. By late embryonic development, some striatal neurons possess DA receptors coupled to IEG (zif268) activation. Postnatally, D1 receptor activation consistently increases zif268 transcription, but the coupling of D2 receptors to zif268 changes from decidedly negative at an early postnatal age to slightly positive in adults. These results are consistent with a role for DA in regulating striatal neuronal differentiation and development.