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.