Although AMPA receptors are known to be widely involved in excitatory synaptic neurotransmission at the spinal level, very little is known about their role in modulating motor activity in mammals. In curarized decerebrate or spinalized rabbit preparations, fictive locomotion was monitored on hindlimb nerves after either activation or blockade of AMPA receptors. In decerebrate preparations, the administration of the antagonist, NBQX (3.5 mg/kg i.p.) or the agonist, AMPA (0.5 mg/kg i.v.) produced, in both cases, a depression of locomotor activities induced by stimulation of cutaneous afferents (evoked locomotor activity). This potent effect was transient with AMPA (recovery after 20 min) and followed by the occurrence of spontaneous locomotor sequences, while no recovery was observed with NBQX treatment. In spinal preparations where a continuous 'spontaneous' locomotor activity resulted from the pharmacological activation of noradrenergic descending pathways (nialamide-DOPA pretreatment), the same drugs injected at higher doses (5 mg/kg NBQX i.p. and 1 mg/kg AMPA i.v.) only weakly affected the frequency of 'spontaneous' and evoked locomotor bursts while they exerted inhibitory and facilitatory effects on the burst amplitude respectively. The results suggest that AMPA receptors are involved at spinal level: 1) in direct mediation of cutaneous afferent excitatory effects on the posterior locomotor generators (pLG); 2) in indirect mediation of a supraspinal descending inhibition controlling, likely presynaptically, the cutaneous afferent activation; and 3) in transmission to motoneurons of the output signals from the pLG. Finally, tight spinal interactions between potent descending noradrenergic pathways and spinal AMPA neurotransmission were disclosed.