Different Effects of Dopamine Antagonists on Spontaneous and NMDA-Induced Motor Activity in Mice

Abstract

The spontaneous motor activity of mice exposed to a new environment is characterized by an initial hyperactivity (explorarory period) followed by low levels of motor activity (habituation period). High doses of the dopamine D 1 receptor antagonist SCH 23390 (1 mg/kg SC) and the dopamine D 2 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.