Sulpiride antagonizes the biphasic locomotor effects of quinpirole in weanling rats.

Low doses of dopamine (DA) agonists such as the D2 receptor subfamily agonist quinpirole are thought to stimulate DA autoreceptors selectively, thereby inhibiting locomotor activity. High doses of quinpirole initially suppress and later activate locomotion during a single test-session; the activation is presumably due to stimulation of postsynaptic receptors. The aim of this study was to investigate whether pretreatment with a selective DA D2 receptor antagonist, sulpiride, could block the putative autoreceptor-mediated inhibition at a lower dose than was required to block the postsynaptically mediated activation. Male and female 30-day-old rats were injected SC with one of eight doses of sulpiride (0.313-40 mg/kg) or the vehicle. Sixty minutes later, rats were injected SC with 0.2 mg/kg quinpirole or the vehicle. Five minutes after the second injection, rats were placed in automated activity monitors which recorded locomotor behavior for 60 min at 5-min intervals. Quinpirole at this dose first suppressed and later increased locomotor activity. Sulpiride pretreatment dose-dependently reversed both the early inhibition and later activation of quinpirole-induced locomotion. However, sulpiride did not block the quinpirole-induced early suppression at a lower dose than was required to block the later activation. Thus, there was no evidence that the locomotor suppression elicited by quinpirole is mediated by a more sensitive subset of DA receptors.