Amalric M, Koob G F
J Neurosci. 1987 Jul;7(7):2129-34. doi: 10.1523/JNEUROSCI.07-07-02129.1987.
Impairment of the dopaminergic system in the brain induced by dopamine-receptor antagonists or by specific neurotoxin terminal lesions results in motor disturbances in rats. In order to specify further the role of the different dopamine pathways in the brain on motor function, the performance of rats trained in an operant reaction-time task was examined after systemic administration of a dopamine-receptor antagonist, alpha-flupenthixol, and after specific destruction of dopamine neurons by 6-hydroxydopamine perfusion into the nucleus accumbens or caudate nucleus. Rats were trained to press a lever and release it as quickly as possible after a light-cue conditioned stimulus (CS). Reaction time was measured from the CS to the release of the lever for each trial. alpha-Flupenthixol (0.2 and 0.4 mg/kg) injected intraperitoneally impaired the reaction-time performance of the rats. While disruption of dopamine activity in the nucleus accumbens did not affect the performance of the rats, lesions of the dopamine terminals of the nigrostriatal pathway in the corpus striatum (59% decrease in posterior striatal dopamine) significantly impaired reaction-time performance. These results show that moderate decreases in dopamine function restricted to the corpus striatum can disrupt sensitive motor performance, and support the hypothesis that dopamine in the corpus striatum has a role in the initiation of complex goal-directed responses.
多巴胺受体拮抗剂或特定神经毒素终末损伤所诱发的大脑多巴胺能系统损伤会导致大鼠出现运动障碍。为了进一步明确大脑中不同多巴胺通路对运动功能的作用,在全身注射多巴胺受体拮抗剂阿立哌唑以及通过向伏隔核或尾状核灌注6-羟基多巴胺特异性破坏多巴胺神经元后,检测了在操作性反应时间任务中训练的大鼠的表现。训练大鼠在光信号条件刺激(CS)后尽快按下杠杆并松开。每次试验测量从CS到杠杆松开的反应时间。腹腔注射阿立哌唑(0.2和0.4毫克/千克)会损害大鼠的反应时间表现。虽然伏隔核中多巴胺活性的破坏并不影响大鼠的表现,但纹状体中黑质纹状体通路多巴胺终末的损伤(纹状体后部多巴胺减少59%)显著损害了反应时间表现。这些结果表明,仅局限于纹状体的多巴胺功能适度降低会破坏灵敏的运动表现,并支持纹状体中的多巴胺在启动复杂的目标导向反应中起作用这一假说。