Specific D1 and D2 dopamine agonists have synergistic effects in the 6-hydroxydopamine circling model in the rat

The effects of SK&F 38393, RU 24213 and quinpirole alone and the synergistic effects of a combination of both subtypes of dopamine agonist on circling behavior were studied in rats with a unilateral lesion of the nigro-striatal pathway. The ability of SCH 23390 and sulpiride to antagonize the synergistic effects induced by SK&F 38393 and RU 24213 in combination were also studied. Finally, the ability of these specific D1 and D2 dopamine antagonists to block the circling induced by two nonspecific dopamine agonists (apomorphine and amphetamine) was investigated. Some animals responded to only one of the selective dopamine agonists but all responded to apomorphine and to the combination of SK&F 38393 plus Ru 24213 or SK&F 38393 plus quinpirole. A powerful synergistic effect was able to antagonize these synergistic effects. The blocking capacity of SCH 23390 and sulpiride was highly diminished in the apomorphine-induced circling model, compared to the amphetamine-induced circling model where normosensitive dopamine receptors are involved. These data suggest an heterogeneous responsiveness to D1, D2D1 plus D2 and mixed D1/D2 dopamine agonists and a strong synergistic effect of the combination of SK&F 38393 plus RU 24213, or SK&F 38393 plus quinpirole. Denervation also induced some changes in the ability of specific dopamine antagonists to block the behavioral response after the administration of non-specific dopamine agonists.