Impairments of movement initiation and execution induced by a blockade of dopamine D1 or D2 receptors are reversed by a blockade of N-methyl-D-aspartate receptors

Abstract

The effects of a dopamine D1 or D2 receptor blockade on initiation and execution of movements were examined using a simple reaction time task for rats. The task demands stimulus-triggered rapid initiation of locomotion to get a food reward. Time and force parameters of the transition from stance to gait were recorded allowing a detailed and separate analysis of the initiation and initial execution of locomotor initiation. Systemic administration of the preferential dopamine D2 antagonist haloperidol (0.1; 0.15 mg/kg, i.p.) caused a delayed movement initiation, as indicated by an increase in reaction time. In addition, movement execution was slowed, as measured by an increase in movement time, a decrease in the rate of development and in the maximum of the accelerative force component. Systemic administration of the selective dopamine D1 antagonist 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390) (0.15 mg/kg, i.p.) induced a similar pattern of impairments as haloperidol. Dizocilpine, an antagonist of the N-methyl-D-aspartate subtype of glutamate receptors in a dose which was largely ineffective when given alone (0.08 mg/kg, i.p.) reversed impairments of movement initiation and execution that were induced by the high dose of dopamine D1 or D2 antagonists (0.15 mg/kg, i.p., respectively). It is concluded that dopamine D1 and D2 receptors are both involved in movement initiation and execution processes, which control the onset and speed of a conditioned movement, as shown here for locomotor initiation of rats. According to our results, the processes related to movement initiation and execution may be mediated by separate neuronal mechanisms, as there were no correlations between impairments of movement initiation and execution, regardless of the treatment animals received. The reversal of SCH 23390- and haloperidol-induced impairments by dizocilpine suggests a functionally antagonistic involvement of dopamine D1/D2 and N-methyl-D-aspartate receptors in the control of movement initiation and execution. The results further imply that neuroleptics blocking dopamine D1 receptors probably induce similar extrapyramidal side effects as classical neuroleptics blocking dopamine D2 receptors.