The D2 autoreceptor agonists SND 919 and PD 128483 decrease stereotypy in developing rats

Although stereotyped behavior in adult rats is partly regulated by dopamine (DA) D2 autoreceptors, previous attempts to demonstrate D2 autoreceptor regulation of stereotypy in developing rats have been unsuccessful. In the present study, two highly selective D2 autoreceptor agonists were used to demonstrate D2 autoreceptor regulation of spontaneous stereotyped behavior in developing rats. Both SND 919 and PD 128483 produced significant dose-dependent decreases in the stereotypy counts of 21-day-old, 35-day-old, and adult rats. There was a 51% decrease in the stereotypy counts of 21-day-old rats injected with SND 919, 0.05 mg/kg, compared to a 36% decrease in the counts of rats pretreated with haloperidol. Similarly, PD 128483 significantly decreased the stereotypy counts of 21-, 35-day-old, and adult rats in a dose-dependent fashion. There was a 58% decrease in the stereotypy counts of 21-day-old rats injected with PD 128483, 0.1 mg/kg, compared to a 17% decrease in counts when the rats were first treated with haloperidol. The effect of haloperidol plus PD 128483 was significantly different from the effect of PD 128483 alone. Injection of SND 919 or PD 128483 had no significant effects on the stereotypy counts of 10-day-old rats. The results suggest that DA D2 autoreceptor-mediated regulation of spontaneous stereotyped behavior is functional at 21, but not 10, days of age.