Competitive NMDA antagonists enhance the catalepsy induced by delta 9-tetrahydrocannabinol in mice

Competitive N-methyl-D-aspartate (NMDA) receptor antagonists, such as CPP and AP-7, dose-dependently enhanced the catalepsy induced by delta 9-tetrahydrocannabinol (THC; 5 mg/kg) in mice, but CPP failed to enhance haloperidol-induced catalepsy. The enhancing effect of CPP on THC-induced catalepsy was dose-dependently blocked by a muscarinic receptor antagonist, scopolamine, and by dopamine D1 and D2 receptor agonists such as apomorphine, SKF 38393 and quinpirole. The effect of CPP was quite opposite to that of the noncompetitive NMDA receptor antagonist MK-801. Therefore, the THC-induced catalepsy model may be useful for distinguishing between both classes of NMDA receptor antagonists.