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

In d-amphetamine-treated (4.0 mg kg(-1) s.c.) rats the selective dopamine D1 and D2/3 receptor antagonists SCH-23390 (2.5-20.0 microg kg(-1) s.c.) and raclopride (12.5-100.0 microg kg(-1) s.c.), respectively, produced a biphasic pattern of effects on forward locomotion, as observed in an open-field arena (approximately 0.5 m2). Thus, at the low doses of SCH-23390 (2.5-10.0 microg kg(-1)) or raclopride (12.5-50.0 microg 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 microg kg(-1)) stimulation of forward locomotion was partially antagonized by concomitant raclopride treatment (12.5-25.0 microg kg(-1)) and the corresponding raclopride-induced (12.5 microg kg(-1)) stimulation was fully antagonized by treatment with SCH-23390 (2.5-5.0 microg kg(-1)). Furthermore, the SCH-23390- or raclopride-induced stimulation of forward locomotion was also antagonized by treatment with the alpha1-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 D2/3 receptors.