Developmental differences in dopamine synthesis inhibition by (±)-7-OH-DPAT

Abstract

Dopamine synthesis modulation by the D₂-family agonist (±)-7-OH-DPAT was explored in striatum, accumbens, and prefrontal cortex of 10–40 day old rats using the gamma-butyrolactone (GBL) autoreceptor model. GBL produced an age-dependent increase in dopamine synthesis that was inhibited by (±) 7-OH-DPAT (0.1–13.5 mg/kg) at all ages and antagonized by eticlopride in the nucleus accumbens and striatum. The ID₅₀ of (±) 7-OH-DPAT increased with age, suggesting decreased autoreceptor sensitivity with maturation. In prefrontal cortex, (±) 7-OH-DPAT inhibited synthesis between 10–30 days, with no evidence of autoreceptor function at 40 days. Dopamine synthesis was also inhibited with the D₃/D₂ agonist quinpirole at 15 days of age in vivo and yielded similar results to those obtained with (±) 7-OH-DPAT. Finally, under conditions that result in low D₂ receptor affinity, D₃ specificity was examined in vitro at 15 days with (±) 7-OH-DPAT, which produced comparable (yet more potent) effects to those observed in vivo. These findings illustrate D₃ autoreceptor-like activity in ascending dopamine regions and provide further support for transient prefrontal cortex autoreceptor-like function that recedes by puberty.