Baunez C, Nieoullon A, Amalric M
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, C.N.R.S. 31, Marseille, France.
Neuroscience. 1995 Mar;65(2):375-84. doi: 10.1016/0306-4522(94)00498-t.
Rats were trained to depress a lever and wait for the onset of a light stimulus, occurring after four equiprobable and variable intervals. At the stimulus onset, they had to release the lever within a reaction time limit for food reinforcement. This paradigm required time estimation of the various intervals and high attentional load for correct performance. Following activation of the dopaminergic transmission after systemic injection of d-amphetamine (0.6 and 0.8 mg/kg) or intrastriatal injection of dopamine (2.5 microgram/microliters), the rat's performance was impaired. Compared with control animals, the performance deficits were expressed as an increased number of premature lever releases before the conditional stimulus onset ("premature responses") and decreased reaction times. Indeed, the reaction times distribution was shifted to the left towards shortened reaction times. Although the number of premature responses was increased, the time estimation of the four different equiprobable intervals was not disturbed after stimulation of dopaminergic activity. A delay-dependent shortening of reaction times as a result of the conditional probability of the stimulus occurrence (i.e. reaction times are shorter as the duration of the delay increases) was found in control and drug sessions, indicating that the animals were still able to prepare their motor response (lever release) even after overstimulation of the dopaminergic transmission. In contrast, blocking dopamine receptors with the selective D2 antagonist raclopride was found to induce opposite effects on the reaction time performance. The number of delayed responses (i.e. occurring with a latency > 600 ms) was found to be significantly enhanced. Furthermore, the reaction times distribution showed a shift of the values to the right revealing a general tendency to lengthened reaction times. These results indicate that a "critical level" of dopamine activity (neither too low nor too high) in the striatum is necessary for a correct execution of the movement in a conditioned motor task with temporal constraint. Moreover, while delayed responses might reflect a motor impairment, anticipatory responses might reflect a "motor facilitation" revealed by a higher level of motor readiness, without disturbing time estimation nor attentional processes.
训练大鼠按压杠杆并等待光刺激出现，光刺激在四个等概率且可变的间隔后发生。在刺激开始时，它们必须在反应时间限制内松开杠杆以获得食物强化。这种范式需要对各种间隔进行时间估计，并具有较高的注意力负荷才能正确执行。在全身注射d-苯丙胺（0.6和0.8毫克/千克）或纹状体内注射多巴胺（2.5微克/微升）后激活多巴胺能传递后，大鼠的表现受损。与对照动物相比，表现缺陷表现为在条件刺激开始前过早松开杠杆的次数增加（“过早反应”）和反应时间缩短。实际上，反应时间分布向左移动，趋向于缩短的反应时间。尽管过早反应的次数增加了，但在刺激多巴胺能活性后，对四个不同等概率间隔的时间估计并未受到干扰。在对照和药物实验中均发现，由于刺激发生的条件概率，反应时间会出现延迟依赖性缩短（即随着延迟持续时间增加，反应时间会缩短），这表明即使在多巴胺能传递过度刺激后，动物仍能够准备好其运动反应（松开杠杆）。相反，发现用选择性D2拮抗剂雷氯必利阻断多巴胺受体会对反应时间表现产生相反的影响。发现延迟反应（即潜伏期>600毫秒时发生的反应）的次数显著增加。此外，反应时间分布显示值向右移动，表明反应时间总体上有延长的趋势。这些结果表明，在有时间限制的条件性运动任务中，纹状体内多巴胺活性的“临界水平”（既不太低也不太高）对于正确执行运动是必要的。此外，虽然延迟反应可能反映运动障碍，但预期反应可能反映由于更高水平的运动准备而揭示的“运动促进”，而不会干扰时间估计或注意力过程。
