Stimulation of forward locomotion by SCH-23390 and raclopride in d-amphetamine-treated rats

Abstract

In d-amphetamine-treated (4.0 mg kg^–1 s.c.) rats the selective dopamine D₁ and D_2/3 receptor antagonists SCH-23390 (2.5–20.0 µg kg^–1 s.c.) and raclopride (12.5–100.0 µg kg^–1 s.c.), respectively, produced a biphasic pattern of effects on forward locomotion, as observed in an open-field arena (≈0.5 m²). Thus, at the low doses of SCH-23390 (2.5–10.0 µg kg^–1) or raclopride (12.5–50.0 µg kg^–1), there was a statistically significant increase in forward locomotion, followed by suppression of the behavior at the higher doses. The SCH-23390-induced (5.0 µg kg^–1) stimulation of forward locomotion was partially antagonized by concomitant raclopride treatment (12.5–25.0 µg kg^–1) and the corresponding raclopride-induced (12.5 µg kg^–1) stimulation was fully antagonized by treatment with SCH-23390 (2.5–5.0 µg kg^–1). Furthermore, the SCH-23390- or raclopride-induced stimulation of forward locomotion was also antagonized by treatment with the α₁-adrenoceptor antagonist prazosin (1.0 mg kg^–1 s.c.). These observations suggest that under conditions of an increased general tone at brain dopamine receptors, there is a mutual inhibitory synergy between dopamine D₁ and D_2/3 receptors.