Synergistic activation of the central pattern generator for locomotion by l-beta-3,4-dihydroxyphenylalanine and quipazine in adult paraplegic mice

Abstract

l-beta-3,4-Dihydroxyphenylalanine ( l-DOPA) and quipazine, respectively dopamine/noradrenaline precursor and serotonergic (5-HT 2) receptor agonist, were injected intraperitoneally in low-thoracic spinal mice at 7 days post-spinalization. In mice pre-treated with decarboxylase and monoamine oxydase inhibitors, l-DOPA (30–100 mg/kg) was found not to induce air-stepping. On the other hand, l-DOPA (40 mg/kg) consistently triggered locomotor-like movements if combined with low doses of quipazine (0.4–0.7 mg/kg) or if mice were placed on a motor-driven treadmill running at low speed. However, twitches, spasms, and other non-locomotor movements were also induced, especially on the treadmill. These results suggest that (1) spinal catecholaminergic and serotonergic receptors interact synergistically to generate locomotor-like movements in chronic spinal mice, and that (2) hindlimb afferent inputs associated with the treadmill conditions contribute to the genesis of locomotor-like and non-locomotor movements induced by these drugs.