The effect of selective D-1 and D-2
dopamine agonists on
catalepsy induced by various
dopamine antagonists was studied. A potent and selective D-2 antagonist, YM-09151 (YM-09151-2) at a dose of 1.2 mg/kg, SC and a selective D-1 antagonist,
SCH 23390 at 1.0 mg/kg, SC induced
catalepsy in rats. Mixed D-1/D-2 antagonists,
haloperidol (HPD) and cis-
flupentixol (FLU) also induced
catalepsy at doses of 2.0 and 0.8 mg/kg, SC, respectively. A mixed D-1/D-2 agonist,
apomorphine (1.0 mg/kg, SC), a selective D-2 agonist,
bromocriptine (10 mg/kg, IP) and a
muscarinic antagonist,
scopolamine (1.0 mg/kg, SC), prevented or markedly reduced the incidence of
catalepsy by the tested antagonists. In contrast, a selective D-1 agonist,
SKF 38393 (4.0 mg/kg, SC) did not reduce the cataleptogenic effects of HPD, FLU and
SCH 23390, but did reduce the effect of YM-09151. Moreover, co-administration of YM-09151 with
SCH 23390 produced a marked increase in the incidence of
catalepsy. The incidence seen after the combination of YM-09151 and
SCH 23390 at low doses was significantly different from that seen after each
drug alone at the doubled dose. Thus, D-1 and D-2 antagonists potentiated each other's effect in producing
catalepsy. These results suggest an important role of both D-1 and D-2 receptors in the
catalepsy and the existence of synergistic effects of D-1 and D-2 receptor blockade.