Hauber W
University of Stuttgart, Department of Animal Physiology, Germany.
Neuroscience. 1996 Jul;73(1):121-30. doi: 10.1016/0306-4522(96)00036-x.
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.
使用大鼠简单反应时任务，研究了多巴胺D1或D2受体阻断对运动起始和执行的影响。该任务要求对刺激做出反应，快速启动运动以获取食物奖励。记录从站立到步态转变的时间和力参数，以便对运动起始的起始和初始执行进行详细且单独的分析。全身给予优先多巴胺D2拮抗剂氟哌啶醇（0.1；0.15mg/kg，腹腔注射）导致运动起始延迟，反应时增加表明了这一点。此外，运动执行减慢，这通过运动时间增加、发育速率降低以及加速力分量最大值降低来衡量。全身给予选择性多巴胺D1拮抗剂盐酸7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓（SCH-23390）（0.15mg/kg，腹腔注射）诱导出与氟哌啶醇类似的损伤模式。单独给予时基本无效的剂量（0.08mg/kg，腹腔注射）的N-甲基-D-天冬氨酸亚型谷氨酸受体拮抗剂地佐环平，可逆转高剂量多巴胺D1或D2拮抗剂（分别为0.15mg/kg，腹腔注射）诱导的运动起始和执行损伤。结论是，多巴胺D1和D2受体均参与运动起始和执行过程，这些过程控制条件性运动的起始和速度，如本研究中大鼠运动起始所示。根据我们的结果，与运动起始和执行相关的过程可能由不同的神经元机制介导 , 因为无论动物接受何种处理，运动起始和执行的损伤之间均无相关性。地佐环平对SCH 23390和氟哌啶醇诱导的损伤的逆转表明，多巴胺D1/D2和N-甲基-D-天冬氨酸受体在运动起始和执行的控制中存在功能拮抗作用。结果还进一步表明，阻断多巴胺D1受体的抗精神病药物可能诱发与阻断多巴胺D2受体的经典抗精神病药物类似的锥体外系副作用。
