Effect of dizocilpine (MK-801) on the catalepsy induced by delta 9-tetrahydrocannabinol in mice

Mice treated with delta 9-tetrahydrocannabinol (THC; 5 and 10 mg/kg i.v.) showed the catalepsy in high bar test, and median descent latencies of catalepsy were about 150 sec. Dizocilpine (MK-801, 0.05 and 0.1 mg/kg), non-competitive N-methyl-D-aspartate (NMDA) antagonist, significantly attenuated THC-induced catalepsy. Furthermore, the anticataleptic effect of MK-801 on THC-induced catalepsy was blocked by acetylcholine agonist oxotremorine (0.005 mg/kg) and dopamine antagonist haloperidol (0.01 mg/kg), but not by NMDA. Oxotremorine, haloperidol, and NMDA themselves did not affect THC-induced catalepsy at the doses used. These results suggest that the anticataleptic effect of MK-801 on THC-induced catalepsy may be developed through dopaminergic and acetylcholinergic neuronal systems.