Synergy between a selective D1 antagonist and a selective D2 antagonist in the induction of catalepsy

The cataleptogenic effects of the selective D1 dopamine receptor antagonist, SCH 23390, and the selective D2 dopamine receptor antagonist, raclopride, when administered alone or in combination were studied in rats using the vertical grid and horizontal bar methods. In either model both agents, given alone, produced dose-dependent catalepsy. When administered together, there was a marked synergy between the two drugs. Thus, a low dose of SCH 23390 resulted in a 10-fold shift to the left of the raclopride dose-effect curve. When the same low dose of SCH 23390 was administered together with a subcataleptogenic dose of raclopride, marked catalepsy was produced. The finding of synergy between selective D1 and D2 dopamine antagonists in the induction of catalepsy suggests that mixed antagonists may possess greater antipsychotic activity than neuroleptics acting mainly on one receptor subtype.