Effects of Intrathecal Glutamatergic Drugs on Locomotion I. NMDA in Short-Term Spinal Cats

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Abstract
Excitatory amino acids (EAA) have been reported to induce fictive locomotion in different in vitro and in vivo preparations in a variety of species through their actions on both N-methyl-d-aspartate (NMDA), and non-NMDA receptors. NMDA-induced intrinsic membrane properties such as intrinsic motoneuronal membrane oscillations and plateau potentials have been suggested to play a role in the generation of locomotion. There is, however, no information on the ability of NMDA in triggering spinal locomotion in awake behaving animals. Because most of the previous work on the induction of locomotion has concentrated on monoaminergic drugs, mainly noradrenergic drugs, the aim of this study is to examine the potential of NMDA in initiating locomotion in chronic spinal cats within the first week after spinalization. Five cats chronically implanted with an intrathecal cannula and electromyographic (EMG) electrodes were used. EMG activity synchronized to video images of the hindlimbs were recorded. The results show that during the early posttransection period (within the 1st week postspinalization), NMDA did not trigger robust locomotion as did noradrenergic drugs. The predominant effects of NMDA were a general hyperexcitability reflected by fast tremor, toe fanning, and an increase in small alternating hindlimb movements with no foot placement nor weight support. During the intermediate phase posttransection (6–8 days), when the cats were able to make some rudimentary steps with foot placement, NMDA significantly enhanced the locomotor performance, which lasted for 24–72 h postinjection. NMDA was also found to increase the excitability of the cutaneous reflex transmission only in early spinal cats. One possible hypothesis for the ineffectiveness of NMDA in triggering locomotion in early spinal cats could be attributed to the widespread activation of NMDA receptors on various neuronal elements involved in the transmission of afferent pathways that in turn may interfere with the expression of locomotion. The marked effects of NMDA in intermediate-spinal cats suggest that NMDA receptors play an important role in locomotion perhaps through its role on intrinsic membrane properties of neurons in shaping and amplifying spinal neuronal transmission or by augmenting the sensory afferent inputs. The long-term effects mediated by NMDA receptors have been reported in the literature and may involve mechanisms such as induction of long-term potentiation or interactions with neuropeptides. The effects of NMDA injection in intact cats and long-term chronic spinal cats will be addressed in a forthcoming companion paper.