EFFECT OF HALOPERIDOL AND (-)-SULPIRIDE ON DOPAMINE AGONIST-INDUCED HYPOACTIVITY

High doses of dopamine D-2 receptor agonists produce hyperactivity in rodents whereas low doses suppress activity. In this study, low doses of a range of dopamine agonists were examined for their effects on loc omotor activity in rats. All agonists caused a dose-related hypolocomo tor effect with a rank order of potency of quinelorane > (-)-quinpirol e > 7-OHDPAT > PBTO. (-)-Sulpiride (1.6-160 mu mol/kg), a neuroleptic with atypical properties caused a dose-related reversal of the hypoloc omotor effect produced by all four agonists whereas the typical neurol eptic haloperidol (0.005-0.16 mu mol/kg) did not reverse hypolocomotio n. Neither sulpiride (5-160 mu mol/kg) nor haloperidol (0.005-0.16 mu mol/kg) affected locomotor activity per se, although haloperidol (1.6- 5 mu mol/kg) did reduce locomotor activity. The different behavioural profiles shown by (-)-sulpiride and haloperidol in these tests may ref lect some of the clinical characteristics of these neuroleptics. The q uestion of whether these effects can be ascribed to differential actio ns at dopamine receptor subtypes will only be answered when more selec tive dopamine receptor antagonists are developed.