Different effects of dopamine antagonists on spontaneous and NMDA-induced motor activity in mice

The spontaneous motor activity of mice exposed to a new environment is characterized by an initial hyperactivity (exploratory period) followed by low levels of motor activity (habituation period). High doses of the dopamine D1 receptor antagonist SCH 23390 (1 mg/kg SC) and the dopamine D2 receptor antagonist raclopride (1 mg/kg SC) partially decreased motor activity during the exploratory period and did not modify motor activity during the habituation period or after reserpinization (5 mg/kg SC 20 h before motor activity recording). The systemic administration of a subconvulsant dose of N-methyl-D-aspartate (NMDA) (75 mg/kg IP) decreased motor activity during the exploratory period and increased motor activity during the habituation period. Both SCH 23390 and raclopride partially counteracted the NMDA-induced motor activation. Neither SCH 23390 nor raclopride counteracted the NMDA-induced motor activation in reserpinized mice. On the contrary, raclopride was found to potentiate the NMDA-induced motor activation in reserpinized animals. The present results suggest the existence of dopamine-dependent and dopamine-independent mechanisms involved in the motor activating effects of NMDA.