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.
Salmi
P
P
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Malmgren
K
K
Svensson
T H
TH
Ahlenius
S
S
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3; D012457:Salicylamides / Q000494:pharmacology*; D013268:Stimulation, Chemical
D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; C493595:Drd3 protein, rat; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; D020891:Raclopride; D006220:Haloperidol; D003913:Dextroamphetamine