Differential behavioural effects of dopamine agonists in developing rats: a study of 3-PPP enantiomers

The effect of different dopamine (DA) agonists on spontaneous activity and d-amphetamine-induced hyperactivity was studied in 11, 20 and 30 day old rats. The proposed selective DA autoreceptor agonist 3-PPP induced biphasic hyperactivity at 11 and 20 days of age, whereas only hypoactivity was observed at 30 days of age, as shown previously for adult rats. The enantiomers of 3-PPP had differential effect: (+)-3-PPP increased activity in 11 and 20 day old rats, where (-)-3-PPP had no effect in similar doses but motility decreased at a higher dose. At 30 days of age (+)-3-PPP decreased motility at low doses and increased motility at a high dose, whereas (-)-3-PPP induced a monotonic decrease, as observed in adult rats. The reference DA agonists apomorphine and pergolide induced only hyperactivity at 11 and 20 days of age. At 30 days the usual sedative effect of low doses was seen. These results confirm that DA autoreceptors mediating sedation are developed later than postsynaptic DA receptors mediating hyperactivity and suggest that 3-PPP (by its (+)-enantiomer) stimulates postsynaptically. (-)-3-PPP had no detectable postsynaptic DA stimulating activity and may, in contrast, act as a postsynaptic antagonist at high doses. Racemic-and (-)-3-PPP antagonized the d-amphetamine-induced hyperactivity at all ages, whereas (+)-3-PPP had no effect and apomorphine was effective at 30 days of age only. These results suggest that the d-amphetamine antagonism by (-)-3-PPP cannot be explained solely by DA autoreceptor stimulation but that autoreceptor stimulation may contribute to the inhibitory effect in mature rats.