Neuromodulation of the locomotor network by dopamine in the isolated spinal cord of newborn rat

We have analysed the action of the neuromodulatory catecholamine, dopamine (DA), on the lumbar locomotor network using an isolated in vitro newborn rat spinal cord preparation. We have also attempted to determine the respective contribution of the D1- and D2-like receptors on the dopamine-mediated effects. Bath application of DA-induced slow locomotor-like rhythmic activity (cycle-period 20-30 s) in ventral motor roots. Bursts were alternating between segmental right and left side and between ipsilateral flexor and extensor units. This rhythm was blocked by D1 (SCH-23390) and D2 (raclopride, sulpiride) receptor antagonists, but was unaffected by the dopamine-beta-hydroxylase blocker, fusaric acid, thereby ruling out indirect noradrenaline-mediated effects. The D1 agonist, SKF-81297 induced prolonged slow rhythmic bursting, while the selective D2 agonists, quinpirole and quinelorane, had no effect. DA and the D1 agonist, SKF-81297 also increased the period and burst amplitude of N-methyl-d-l-aspartate-induced locomotor activity. The effects of dopamine and SKF-81297 on the N-methyl-d-l-aspartate-induced rhythm were long-lasting; persisting for 1 hour after washout. The DA action was blocked by MDL-12 330 A, an inhibitor of adenylate cyclase, suggesting the involvement of cAMP. Together these results indicate that dopamine can exert neuromodulatory actions on mammalian motor networks via short-lasting permissive influences and a newly reported, long-lasting modulation of motor network activity.