Barbeau H, Rossignol S
Département de Physiologie, Faculté de Médecine Université de Montréal, Qué., Canada.
Brain Res. 1991 Apr 19;546(2):250-60. doi: 10.1016/0006-8993(91)91489-n.
The effects of noradrenergic, serotonergic and dopaminergic drugs, and their interaction were studied in 8 adult spinal cats during the first week following spinalisation and up to 3 months, when the animals had reached a steady state in their locomotor pattern. During the first week, when no episodes of coordinated stepping were observed, injection of the serotonergic precursor (DL-5-HTP) or a dopaminergic agonist (apomorphine) failed to induce locomotion. In contrast, injection of either a noradrenaline precursor (L-DOPA) or an agonist (clonidine) induced locomotion when the hindlimbs were placed on a moving belt. The spinal animal demonstrated a bilateral foot placement on the plantar surface, as well as transient weight support of the hindquarters at a treadmill speed up to 0.80 m/s. The movement pattern and the electromyographic activity resemble those of the intact cat in many aspects. This locomotion-triggering effect of L-DOPA or clonidine was also observed when given after DL-5-HTP or apomorphine. At around 3 months following spinalisation, when the animal showed a stable and regular locomotor pattern, injection of clonidine increased the step cycle duration, resulting in a prolonged flexor and extensor burst duration as the EMG amplitude was unchanged or slightly increased. Injected in the same animal, quipazine, a serotonergic agonist, increased both the duration and the amplitude of flexor and extensor EMGs. In contrast to the serotonergic and the noradrenergic agonists, apomorphine and L-DOPA augmented mainly the flexor activity which could even lead to a sustained flexion when the dose was increased. When combining clonidine to a serotonergic drug, the characteristics of the modulation of the locomotor pattern resulting from each drug were retained. The present results demonstrate that (1) the noradrenergic system is probably the most important system for the initiation of locomotion; (2) the three monoaminergic descending systems (mimicked by the precursor and agonists) can modify rather specifically different aspects of the well established locomotor pattern in the same chronic spinal cat and (3) the effect of monoaminergic drugs are reproducible when given in similar time periods in different chronic spinal cats. The present study provides insight into the role of the noradrenergic, serotonergic and dopaminergic system in the initiation and in the modulation of the locomotion pattern following spinalisation. The above studies also provide a basis to investigate the effects of these drugs in spinal cord-injured patients.
在成年脊髓猫脊髓损伤后的第一周直至3个月期间（此时动物的运动模式已达到稳定状态），研究了去甲肾上腺素能、血清素能和多巴胺能药物的作用及其相互作用。在第一周，当未观察到协调性踏步发作时，注射血清素能前体（DL-5-羟色氨酸）或多巴胺能激动剂（阿扑吗啡）未能诱发运动。相反，当后肢置于移动带上时，注射去甲肾上腺素前体（左旋多巴）或激动剂（可乐定）可诱发运动。脊髓动物在跑步机速度高达0.80米/秒时，表现出双侧足部在足底表面的放置以及后躯的短暂承重。运动模式和肌电图活动在许多方面类似于完整猫的情况。在注射DL-5-羟色氨酸或阿扑吗啡后给予左旋多巴或可乐定，也观察到这种运动触发效应。在脊髓损伤后约3个月，当动物表现出稳定且规律的运动模式时，注射可乐定可增加步周期持续时间，导致屈肌和伸肌爆发持续时间延长，此时肌电图振幅未变或略有增加。在同一动物中注射血清素能激动剂喹哌嗪，可增加屈肌和伸肌肌电图的持续时间和振幅。与血清素能和去甲肾上腺素能激动剂不同，阿扑吗啡和左旋多巴主要增强屈肌活动，当剂量增加时甚至可导致持续屈曲。当将可乐定与血清素能药物联合使用时，每种药物对运动模式调节的特征得以保留。目前的结果表明：（1）去甲肾上腺素能系统可能是启动运动最重要的系统；（2）三个单胺能下行系统（由前体和激动剂模拟）可在同一慢性脊髓猫中相当特异性地改变已确立的运动模式的不同方面；（3）在不同慢性脊髓猫的相似时间段给予单胺能药物时，其效果是可重复的。本研究深入了解了去甲肾上腺素能、血清素能和多巴胺能系统在脊髓损伤后运动模式启动和调节中的作用。上述研究也为研究这些药物对脊髓损伤患者的影响提供了基础。
