Dopamine D₁ autoreceptor function: possible expression in developing rat prefrontal cortex and striatum

Synthesis-modulating dopamine (DA) autoreceptor function was studied in vivo using γ-butyrolactone (GBL) to block propagation along DA axons. DA synthesis was measured by the accumulation of l-3,4-dihydroxyphenylalanine (l-DOPA) after inhibition of aromatic l-amino acid decarboxylase. GBL treatment markedly increased DOPA accumulation in both the striatum and prefrontal cortex of developing rats. The selective DA partial D₁ agonist SKF-38393 inhibited this GBL-induced rise in DA synthesis in both the striatum and prefrontal cortex of 15- and 22-day-old rats, but not in adults. The effects of SKF-38393 in developing rats were mimicked by the non-catechol D₁ partial agonist CY-208-243, and were blocked by the D₁ antagonist SCH-23390, suggesting receptor mediation. The mixed D₂/D₃ agonist quinpirole attenuated DA synthesis in striatum of both two-week-old and adult rats, but failed to inhibit the GBL-induced increase in DA synthesis in the developing prefrontal cortex. These findings suggest that synthesis-modulating D₁-like receptor function may emerge transiently in the developing mammalian forebrain. In the adult striatum these functions appear to be subsumed by D₂-like receptors, whereas all synthesis-modulating DA receptor function in prefrontal cortex appears to be essentially lost with maturation.