Downregulation of stereotyped behavior and production of latent locomotor behaviors in mice treated continuously with quinpirole.
D1 and D2 dopamine receptors mediate different behavioral effects in animals. We have attempted to selectively modulate dopamine-mediated behaviors by continuously administering D2 agonists to mice. Acute administration of the D2 agonist quinpirole caused dose-related stereotyped effects; no locomotor or grooming behavior was apparent. Continuously infusing quinpirole with implanted Alzet minipumps initially produced stereotyped behavior, but this stereotypy decreased by 2 hours, and was completely absent from 3 hours to 6 days of infusion. Within 1 day after implanting quinpirole, there appeared a significant locomotor behavior that continued for the 6 days of infusion. Acute challenge doses of quinpirole given either 6 days after infusing quinpirole or 12 hours after removing the quinpirole implant failed to elicit any stereotyped behavior and did not alter the locomotor behavior. By contrast, acute challenge injections with the D1 agonist SKF 38393 administered 12 hours after removing the quinpirole implant produced a characteristic grooming response. In an attempt to learn the mechanism of the behavioral effects induced by the continuous administration of quinpirole, the actions of relatively selective D1 and D2 antagonists were examined. The D2 antagonist sulpiride inhibited the stereotypy but not the locomotion induced by quinpirole. By contrast, the D1 antagonist Sch 23390 blocked the locomotion but not the stereotypy induced by quinpirole. These results indicate that chronic administration of quinpirole causes two separate behavioral effects: (1) a downregulation of stereotypy, perhaps by downregulating D2 receptors; and (2) the development of locomotion, which appears to involve both the downregulation of D2 receptors and an activation of D1 dopaminergic mechanisms.
Zhou
L W
LW
Department of Pharmacology, Medical College of Pennsylvania/EPPI, Philadelphia 19129.
Qin
Z H
ZH
Weiss
B
B
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004343:Drug Implants; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012016:Reference Values; D013239:Stereotyped Behavior / Q000187:drug effects*
D001552:Benzazepines; D015259:Dopamine Agents; D004343:Drug Implants; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine