Noradrenergic agonists and locomotor training affect locomotor recovery after cord transection in adult cats

Abstract

In one series of experiments, the effects of noradrenergic, serotonergic and dopaminergic precursors and agonists on the initiation of locomotion were investigated within the first week after complete spinalization at +13 in five adult cats. In addition, the effects of clonidine and daily locomotor training were investigated during the first week after transection in another cat. The electromyographic (EMG) activity of vastus lateralis (VL) and semitendinosus (St) was recorded bilaterally through percutaneously implanted copper wires in all cats. The movement of the hindlimbs on the treadmill was also simultaneously videorecorded before and after the injection of drugs. Without drug injection, strong and sustained perineal or abdominal stimulation did not induce any prolonged episodes of coordinated stepping on the treadmill during the first week after spinalization. St often had sustained activity, in contrast to VL, in which minimal or no activity was present. Injection of apomorphine (0.3 to 0.5 mg/kg, n = 3), a dopaminergic agonist, or DL-5-HTP (50 mg/kg, n = 2), a serotonergic precursor, failed to induce locomotion at such an early stage after spinalization. In contrast, injection of either L-dopa (50–60 mg/kg, n = 2), a noradrenergic precursor, or clonidine ( 150 Mg/kg, n = 2), a noradrenergic agonist, induced locomotion on the treadmill. The animal demonstrated bilateral foot placement on the soles and complete weight support of the hindquarters. The spinal cat could follow the treadmill speed up to 0.80 ms −1. However, these effects disappeared when the NA drugs were tapered off. When the spinal cat was trained daily under the effect of clonidine, a stable locomotor pattern was established within 1 week post-transection, which was retained afterwards even without clonidine injection. This locomotor pattern is similar, in many aspects, to that observed in the chronic stage after an intensive program of locomotor training, 2 to 3 months posttransection, without clonidine injection (1). The present results confirm previous studies showing that locomotion cannot be elicited spontaneously in the first week after spinalization. We further demonstrate that L-dopa and clonidine, but not apomorphine or 5-HTP, are each capable of inducing locomotion in the first week after spinalization. These results also support that the combination of clonidine and locomotor training can accelerate the recovery of locomotion, since a well-developed locomotor pattern could be observed in as early as the first week post-transection.