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 intrathecall y) on treadmill locomotion were evaluated in two adult cats subjected to a ventral and ventrolateral spinal lesion (T-13). Despite the extensive spina l lesion, severely damaging important descending pathways such as the retic ulo- 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 wi th its hindlimbs, recovery period, when progressive improvement occurred, a nd 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 in consistent 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 we re implanted chronically with an intrathecal cannula and electromyographic (EMG) electrodes, which allowed determination, under similar recording cond itions, of the locomotor performance pre- and postlesion and comparisons of the effects of different drugs. EMG and kinematic analyses showed that nor epinephrine (NE) injected in early and plateau periods improved the regular ity of the hindlimb stepping and stabilized the interlimb coupling, permitt ing to maintain constant locomotion for longer periods of rime. Methoxamine , the alpha(1)-agonist (tested only at the plateau period), had similar eff ects. In contrast, the alpha(2)-agonist, clonidine, deteriorated walking. S erotoninergic drugs, such as the neurotransmitter itself, serotonin (5HT)I the precursor 5-hydroxytryptophan (5HTP), and the agonist quipazine improve d the locomotion by increasing regularity of thee hindlimb stepping and by increasing the step cycle duration. In contrast, the 5HT(1A) agonist 8-hydr oxy-dipropylaminotetralin (DPAT) caused foot drag in one of the cats, resul ting in frequent stumbling. Injection of combination of methoxamine and qui pazine resulted in maintained, regular stepping with smooth movements and g ood lateral stability. Our results show that the effects of drugs can be in tegrated to the residual voluntary locomotion and improve some of its postu ral aspects. However, this work shows clearly that the effects of drugs (su ch 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 c ould be used in patients with different types of spinal cord injuries. Poss ible mechanisms underlying the effect of noradrenergic and serotoninergic d rugs on the locomotion after partial spinal lesions are discussed.