Behavioral effects of D1 and D2 dopamine receptor antagonists in squirrel monkeys

The behavioral effects of dopamine antagonists differing in affinity and selectivity at D1 and D2 dopamine receptors were compared in squirrel monkeys responding under a fixed-interval schedule of stimulus-shock termination. D1-selective antagonists included (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol, SCH 23390; its enantiomer (S)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol, SCH 23388; [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H - benzo(d)naphtho-(2,1-b)azepine], SCH 39166; (R)-7-bromo-8-hydroxyl-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pine, R-SKF 83566; (R)-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol, R-SKF 83692; 2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol, RS-SKF 83692. D2-selective antagonists included cis-N-(1-benzyl-2-methylpyrrolidine-3-yl)-5-chloro-2-methoxy-4- methylaminobenzamide, YM-09151-2, eticlopride, raclopride, haloperidol, risperidone, remoxipride, S-sulpiride and R-sulpiride; nonselective dopamine antagonists were S-butaclamol and chlorpromazine. Regardless of selectivity for D1 or D2 receptors, all drugs produced dose-related decreases in fixed-interval responding. A high degree of stereoselectivity was evident for both D1 antagonists (SCH 23390 and R-SKF 83692 more potent than, respectively, SCH 23388 and RS-SKF 83692) and D2 antagonists (S-sulpiride more potent than R-sulpiride). High doses of the D1 and D2 antagonists also reduced motor activity and impaired coordination in monkeys in the home cage after test sessions.(ABSTRACT TRUNCATED AT 250 WORDS)