Synergistic and persistent interaction between the D2 agonist, bromocriptine, and the D1 selective agonist, CY...

In mice pretreated with reserpine and alpha-methyl-DL-p-tyrosine (alpha MPT) to deplete central catecholamines, the D2 dopamine receptor-selective agonist, bromocriptine, at a dose of 10 mg/kg produced no locomotor activity. The D1-selective agonist, CY 208-243, generated a dose-dependent locomotor response in this animal model for Parkinson's disease; low doses elicited little or no effect while higher doses resulted in a short burst of locomotor activity (2 h). The combination of CY 208-243 and bromocriptine had a dramatic synergistic effect on locomotion. Most importantly, this combination of D1 and D2 agonists converted a brief (2 h) effect on locomotion to one which persisted for up to 6 h. These results suggest that the combination of D1 and D2 dopamine receptor agonists can affect both the intensity and the persistence of a locomotor response.