The effect of 4-aminopyridine on the spinal locomotor rhythm induced by L-DOPA.

In high spinal curarized cats rhythmic motor output similar to locomotion ('fictive locomotion') of all 4 limbs was obtained after intravenous application of the noradrenergic precursor, L-DOPA, and nialamide combined with 4-aminopyridine (4-AP). The activity was recorded from muscle nerves. In the presence of 4-AP, which enhances transmission at various excitatory and inhibitory synapses, reduced amounts of DOPA were sufficient to evoke fictive locomotion. 4-AP alone did not elicit locomotion. The burst rate increased up to 6 Hz with the amount of 4-AP given (0.5-50 mg/kg). The cyclic frequency of high spinal cats exhibiting either fictive locomotion or walking on a treadmill was accelerated by 4-AP. After a supplementary transection of the spinal cord at the upper lumbar level both fore- and hindlimbs generally continued to show fictive locomotion with similar frequencies. In the presence of high doses of clonidine (alpha-receptor-activator, greater than 4 mg/kg), the locomotor pattern was replaced by regular (2 Hz) synchronous discharges in all flexors and extensors.