Dopaminergic drugs differing in efficacy may have qualitatively different behavioral effects in monkeys that may reflect dissimilar therapeutic applications in clinical settings. The present studies were conducted to characterize such differences by comparing the effects of D1 and D2 antagonists (SCH 39166 and remoxipride), partial agonists (SKF 77434 and SDZ 208-911), and full agonists (dihydrexidine and (+)-PHNO) in squirrel monkeys trained to discriminate injections of methamphetamine from saline. Both the D1 and D2 full agonists generally substituted for methamphetamine whereas the partial D1 and D2 partial agonists generally failed to reproduce the effects of methamphetamine. Similar to the effects of D1 and D2 receptor antagonists, both the partial agonists SKF 77434 and SDZ 208-911 surmountably antagonized the discriminative-stimulus effects of methamphetamine. These results indicate that the interoceptive effects of methamphetamine can be mimicked by agonists that selectively stimulate either the D1 or D2 type of dopamine receptor. Furthermore, the behavioral effects of partial agonists at D1 and D2 receptors may be comparable to those of antagonists at those receptors. These latter findings suggest that dopamine partial agonists might be developed as medications to counteract the subjective effects of methamphetamine.
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