Initiation and modulation of the locomotor pattern in the adult chronic spinal cat by noradrenergic, serotonergic and dopaminergic drugs

Abstract

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.