Comparison of the effect of intrathecal administration of clonidine and yohimbine on the locomotion of intact and spinal cats

Several studies have shown that noradrenergic mechanisms are important for locomotion. For instance, L-dihydroxyphenylalanine (L-DOPA) can initiate "f ictive" locomotion in immobilized acutely spinalized cats and alpha (2)-nor adrenergic agonists, such as 2,6,-dichloro-N-2-imidazolidinylid-enebenzenam ine (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 be cause the descending pathways are completely severed. This suggests that lo comotion, in intact and spinal conditions, is probably expressed and contro lled through different neurotransmitter mechanisms. To test this hypothesis , we compared the effect of the ct, agonist, clonidine, and the antagonist (16 alpha, 17 alpha)-17-hydroxy yohimbine-16-carboxylic acid methyl ester h ydrochloride (yohimbine), injected intrathecally at L-3-L-4 before and afte r spinalization in the same cats chronically implanted with electrodes to r ecord electromyograms (EMGs). In intact cats, clonidine (50-150 mug/100 mul ) modulated the locomotor pattern slightly causing a decrease in duration o f the step cycle accompanied with some variation of EMG burst amplitude and duration. In the spinal state, clonidine could trigger robust and sustaine d 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 s table 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 mug/100 mul) caused major walking difficulties characterized by as ymmetric stepping, stumbling with poor lateral stability, and, at smaller d oses (400 mug/100 mul), only had slight effects such as abduction of one of the hindlimbs and the turning of the hindquarters to one side. After spina lization, yohimbine had no effect even at the largest doses. These results indicate that, in the intact state, noradrenergic mechanisms probably play an important role in the control of locomotion since blocking the receptors results in a marked disruption of walking. In the spinal state, although t he receptors are still present and functional since they can be activated b y clonidine, they are seemingly not critical for the spontaneous expression of spinal locomotion since their blockade by yohimbine does not impair spi nal locomotion. It is postulated therefore that the expression of spinal-lo comotion must depend on the activation of other types of receptors, probabl y related to excitatory amino acids.