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Journal of Neuroscience, Vol 13, 990-1000, Copyright © 1993 by Society for Neuroscience
The effects of intrathecal administration of excitatory amino acid agonists and antagonists on the initiation of locomotion in the adult cat
JR Douglas, BR Noga, X Dai and LM Jordan
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Development of pharmacological strategies for the control of locomotion in
patients with spinal cord injury or disease requires an understanding of
the neuroactive substances involved in the activation of the spinal cord
neural systems for the control of locomotion. Studies using the in vitro
preparations of the lamprey, frog embryo, and newborn rat indicate that
excitatory amino acids (EAAs) are involved in the initiation of locomotion.
The present study determines whether spinal EAA receptors play a role in
locomotion in an in vivo, adult mammalian preparation. Experiments were
performed on precollicular, postmammillary decerebrate cats, some of which
were spinalized at the 13th thoracic segment. Cannulas for drug infusions
were positioned intrathecally in the lumbar region of the spinal cord. A
ligature around the spinal cord at the level of the 13th thoracic segment
prevented rostral diffusion of the drugs. Locomotion was monitored with
electromyograms in treadmill locomotion experiments and electroneurograms
in fictive locomotion experiments. Intrathecal infusion of either the NMDA
receptor antagonist 2-amino-5- phosphonovaleric acid or the non-NMDA
receptor antagonist 6-cyano-7- nitroquinoxaline-2,3-dione blocked hindlimb
treadmill and fictive locomotion induced by electrical stimulation of the
mesencephalic locomotor region (MLR) of the midbrain. Intrathecal
administration of NMDA elicited hindlimb fictive locomotion in resting
animals similar to that evoked by electrical stimulation of the MLR. At
lower concentrations, NMDA evoked either independent bursting activity in
the various nerves or loosely organized rhythmicity showing little
reciprocity between antagonists. In contrast, administration of the EAA
uptake blocker dihydrokainic acid (DHK) evoked intermittent periods of
bursting activity characterized by a variable duration and a high degree of
reciprocity between flexors and extensors. Given together at low
concentrations, NMDA and DHK produced a well-coordinated locomotor pattern.
Kainate and quisqualate were ineffective in producing fictive locomotion.
These results are consistent with the suggestion that EAAs play a role in
the initiation of mammalian locomotion. Furthermore, the results are
consistent with those obtained from the neonatal rat in vitro preparations.
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