The D1 agonist SKF 38393 increases dopamine release in the developing rat striatum

Changes in extracellular levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) following systemic injection of the D1 agonist SKF 38393, 10 mg/kg, the D1 antagonist SCH 23390, 0.5 mg/kg, or the mixed D1/ /D2 agonist apomorphine, 0.05 mg/kg, were monitored in the striatum of developing rats implanted with a dialysis probe. There was a significant age-related increase in DA in perfusates from adult and 35-36-day-old rats injected with SKF 38393 compared to 10-11- and 21-22-day-old rats. Also, SKF 38393 significantly decreased DOPAC and HVA in perfusates from 10-11-day-old rats when compared to the older aged rats. Pretreatment with SCH 23390 completely blocked the SKF 38393-induced increase in DA but not the SKF 38393-induced decrease in DOPAC and HVA. In contrast, there were no significant differences between ages in the response to DA to SCH 23390. However, SCH 23390 did produce a small, but significant, decrease in DOPAC and HVA at 10-11 days of age compared to the other ages. Forty minutes after injecting apomorphine, DA levels were decreased by 45% and remained near this level for the duration of the experiment. These results indicate that stimulation of DA D1, receptors can increase striatal DA release and that this ability is acquired between 21 and 35 days of age. This finding is consistent with the idea of opposing roles for DA D1 and D2 receptor subtypes.