SCH 23390 may alter dopamine-mediated motor behaviour via striatal D-1 receptors.
SCH 23390 potently displaced the specific binding of 3H-piflutixol to D-1 sites in striatal membranes but haloperidol was only weakly effective. SCH 23390 weakly displaced specific 3H-spiperone binding to D-2 sites, but haloperidol was potent. SCH 23390 was more effective than haloperidol in inhibiting dopamine stimulated striatal adenylate cyclase activity. These results confirm the D-1 selectivity of SCH 23390. However, SCH 23390 inhibited apomorphine-induced stereotypy and climbing behaviour in rats with equal potency to haloperidol. Haloperidol dose-dependently increased striatal HVA and DOPAC concentrations without altering dopamine content. Low doses of SCH 23390 elevated striatal DOPAC concentrations but higher doses were without effect; striatal dopamine and HVA overall was unaffected by administration of SCH 23390. Haloperidol did not affect basal 3H-acetylcholine release from striatal slices but reversed the apomorphine-induced inhibition of 3H-acetylcholine release. SCH 23390 did not affect basal 3H-acetylcholine release nor did it reverse the apomorphine-induced inhibition of 3H-acetylcholine release. The ability of SCH 23390 to inhibit motor behaviour in the rat may be due to its action on D-1 receptors since the drug does not cause typical changes in parameters of striatal D-2 receptor function.
Boyce
S
S
Kelly
E
E
Davis
A
A
Fleminger
S
S
Jenner
P
P
Marsden
C D
CD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013892:Thioxanthenes / Q000378:metabolism
D001552:Benzazepines; D011954:Receptors, Dopamine; D013892:Thioxanthenes; D015102:3,4-Dihydroxyphenylacetic Acid; D013134:Spiperone; D000242:Cyclic AMP; C015448:piflutixol; D001058:Apomorphine; D000109:Acetylcholine; D004298:Dopamine