Locomotor activity and motor disturbances induced by the competitive NMDA receptor antagonist CGP 37849

The study compares the effects of the competitive NMDA receptor antagonist, CGP 37849, on the locomotor activity and motor disturbances after local, unilateral microinjection into nucleus accumbens and caudateputamen or peripheral ip administration. Independently on the route of administration, the compound induced dose-dependent increase in the locomotor activity as well as the symptoms of motor disturbances. In all cases the symptoms of motor disturbances appeared earlier and lasted longer than increase in locomotor activity induced by the same dose of the drug. The long-lasting observation indicated, that CGP 37849 administered in a dose of 20 mg/kg ip increased the locomotor activity of the rats for about 2 h while motor disturbances persisted for about 6 h. Administration of the lowest dose of CGP 37849, i.e. 0.05 microgram into the nucleus accumbens, or 10 mg/kg ip-while without any effect on the locomotor activity-induced the symptoms of motor disturbances. Pretreatment with SKF-525-A (proadifen, an agent inhibiting the metabolism of the drugs), fully antagonized the locomotor hyperactivity induced by CGP 37849 given in a dose of 20 mg/kg, and-in the same time-diminished the degree of motor disturbance symptoms. On the other hand, in the case of the dose of 10 mg/kg of CGP 37849, SKF-525-A did not affect the locomotor activity, but enhanced the motor disturbance symptoms induced by this dose of CGP 37849. In conclusion, the obtained results indicate that CGP 37849 administered peripherally or locally to the brain regions cited above induces motor disturbances at doses lower (or at least similar) than these which stimulate the locomotor activity.