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The Journal of Neurophysiology Vol. 81 No. 4 April 1999, pp. 1513-1530
Copyright ©1999 by the American Physiological Society
Centre de recherche en Sciences Neurologiques, Faculté de Médecine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada
Brustein, Edna and
Serge Rossignol.
Recovery of locomotion after ventral and ventrolateral spinal
lesions in the cat. II. Effects of noradrenergic and serotoninergic drugs. The effects of serotoninergic and noradrenergic drugs
(applied intrathecally) on treadmill locomotion were evaluated in two
adult cats subjected to a ventral and ventrolateral spinal lesion
(T13). Despite the extensive spinal lesion, severely
damaging important descending pathways such as the reticulo- and
vestibulospinal tracts, both cats recovered quadrupedal voluntary
locomotion. As detailed in a previous paper, the locomotor recovery
occurred in three stages defined as early period, when the
animal could not walk with its hindlimbs, recovery period,
when progressive improvement occurred, and plateau period,
when a more stable locomotor performance was observed. At this latter
stage, the cats suffered from postural and locomotor deficits, such as
poor lateral stability, irregular stepping of the hindlimbs, and
inconsistent homolateral fore- and hindlimb coupling. The present study
aimed at evaluating the potential of serotoninergic and/or
noradrenergic drugs to improve the locomotor abilities in the early and
late stages. Both cats were implanted chronically with an intrathecal
cannula and electromyographic (EMG) electrodes, which allowed
determination, under similar recording conditions, of the locomotor
performance pre- and postlesion and comparisons of the effects of
different drugs. EMG and kinematic analyses showed that
norepinephrine (NE) injected in early and plateau periods
improved the regularity of the hindlimb stepping and stabilized the
interlimb coupling, permitting to maintain constant locomotion for
longer periods of time. Methoxamine, the
1-agonist (tested only at the plateau period), had
similar effects. In contrast, the 2-agonist,
clonidine, deteriorated walking. Serotoninergic drugs, such
as the neurotransmitter itself, serotonin (5HT), the
precursor 5-hydroxytryptophan (5HTP), and the agonist
quipazine improved the locomotion by increasing regularity
of the hindlimb stepping and by increasing the step cycle duration. In
contrast, the 5HT1A agonist 8-hydroxy-dipropylaminotetralin (DPAT) caused foot drag in one of the cats,
resulting in frequent stumbling. Injection of combination of
methoxamine and quipazine resulted in maintained, regular stepping with
smooth movements and good lateral stability. Our results show that the
effects of drugs can be integrated to the residual voluntary locomotion and improve some of its postural aspects. However, this work shows clearly that the effects of drugs (such as clonidine) may depend on
whether or not the spinal lesion is complete. In a clinical context,
this may suggest that different classes of drugs could be used in
patients with different types of spinal cord injuries. Possible
mechanisms underlying the effect of noradrenergic and serotoninergic
drugs on the locomotion after partial spinal lesions are discussed.
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