Comparison of the Effect of Intrathecal Administration of Clonidine and Yohimbine on the Locomotion of Intact and Spinal Cats

Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Faculté de Médecine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada Giroux, Nathalie, Tomás A. Reader, and Serge Rossignol. Comparison of the Effect of Intrathecal Administration of Clonidine and Yohimbine on the Locomotion of Intact and Spinal Cats. J. Neurophysiol. 85: 2516-2536, 2001. Several studies have shown that noradrenergic mechanisms are important for locomotion. For instance, L-dihydroxyphenylalanine (L-DOPA) can initiate "fictive" locomotion in immobilized acutely spinalized cats and 2 -noradrenergic agonists, such as 2,6,-dichloro- N -2-imidazolidinylid-enebenzenamine (clonidine), can induce treadmill locomotion soon after spinalization. However, the activation of noradrenergic receptors may be not essential for the basic locomotor rhythmicity because chronic spinal cats can walk with the hindlimbs on a treadmill in the absence of noradrenergic stimulation because the descending pathways are completely severed. This suggests that locomotion, in intact and spinal conditions, is probably expressed and controlled through different neurotransmitter mechanisms. To test this hypothesis, we compared the effect of the 2 agonist, clonidine, and the antagonist (16 , 17 )-17-hydroxy yohimbine-16-carboxylic acid methyl ester hydrochloride (yohimbine), injected intrathecally at L 3 -L 4 before and after spinalization in the same cats chronically implanted with electrodes to record electromyograms (EMGs). In intact cats, clonidine (50-150 µg/100 µl) modulated the locomotor pattern slightly causing a decrease in duration of the step cycle accompanied with some variation of EMG burst amplitude and duration. In the spinal state, clonidine could trigger robust and sustained hind limb locomotion in the first week after the spinalization at a time when the cats were paraplegic. Later, after the spontaneous recovery of a stable locomotor pattern, clonidine prolonged the cycle duration, increased the amplitude and duration of flexor and extensor bursts, and augmented the foot drag at the onset of swing. In intact cats, yohimbine at high doses (800-1600 µg/100 µl) caused major walking difficulties characterized by asymmetric stepping, stumbling with poor lateral stability, and, at smaller doses (400 µg/100 µl), only had slight effects such as abduction of one of the hindlimbs and the turning of the hindquarters to one side. After spinalization, yohimbine had no effect even at the la