Phyalology and Behavior, Vol. 6, pp. 627-628. Pergamon Press, 1971. Printed in Great Britain

BRIEF COMMUNICATION

Facilitation by Strychnine of Reflex Walking in Spinal Dogs'

B E N J A M I N L. H A R T

Department of Anatomy, University of California, Davis, California, U.S.A.

(Received 17 September 1970)

HART, B. L. Facilitation by strychnine of reflex walking in .spinal dogs. PHYSIOL. BEHAV. 6 (5) 627-628, 1971.--Results of previous studies have indicated that the spinal dog is incapable of reflex walking. In the present experiment sub- convulsive doses of strychnine sulfate were given to non-walking spinal dogs and within a few minutes these animals displayed reflex walking. Two spinal dogs capable of moderate reflex walking before strychnine administration greatly improved their walking performance following administration of the drug. Since strychnine is believed to suppress postsynaptic inhibition, these observations suggest that the facilitation of reflex walking is due to a reduction of tonic intraspinal inhibition which is otherwise strong enough to prevent the occurrence of reflex walking in most spinal dogs.

Strychnine Locomotor behavior Reflexes Spinal cord

AMONG the many complex spinal reflexes studied by Sherring- ton and his associates [1, 7, 8] in the chronic spinal dog were reflex standing and stepping. Evidently Sherrington [8] as well as more recent workers [3, 5] who have studied the reflex activity of the back legs of the spinal dog, believed this prepara- tion to be incapable of reflex walking. Ten Cate [11] in reviewing conflicting opinions regarding reflex walking expressed by French and German investigators, points to observations suggesting that the apparent walking activity shown by some spinal dogs was simply a reflection of the ability of the spinal animal to hold the posterior region horizontal, by using the front legs as a fulcrum and lowering the head as a counterweight. Shurrager and Dykman [9, 10] who studied the development of reflex walking in kittens and a puppy presented evidence suggesting a learning of reflex walking by the postnatal spinal cord. These investigators felt that this type of learning was difficult or impossible for the spinal cord of the adult.

In a series of previous investigations using chronic spinal dogs, the author has had occasion to observe and monitor somatic reflexes in these animals as long as 200 days after transection. Reflex walking was observed in two animals, but this activity was not normally displayed by the large majority of healthy chronic spinal dogs. On one occasion a subconvulsive dose (0.1 mg/kg) of strychnine sulfate was given intravenously to one of the non-walking spinal dogs and within a few minutes the animal exhibited strong reflex walking. Subsequently, as reported in this communication, systematic observations were made on the influence of strych- nine on reflex walking of eight spinal dogs transected in adulthood.

METHOD

Three adult male and five adult female beagles used in previous experiments for the study of sexual reflexes were employed. A spinal transection had been performed on all animals in the thoracic (Te-T10) region. The procedure for the spinal transection has been described elsewhere [4]. Somatic reflex activity was monitored at weekly intervals starting one week after transection. By 40-50 days after transection reflex function had stabilized.

During the 100-200 day postoperative period spinal re- flexes were tested before and after intravenous administration of a subconvulsive dose of strychnine sulfate at the rate of 0.1 mg/kg. Flexion, crossed extension, extensor thrust, scratch, and tendon jerk reflexes were tested with the animal in lateral recumbency. Reflex stepping was tested by grasping the animal around the chest region and allowing the back legs to hang freely. This generally evoked rhythmic stepping of the rear legs. Reflex walking was tested by taking the animals to a grassy field and allowing them to move about freely.

RESULTS AND DISCUSSION

Following strychnine administration there was the expected moderate facilitation of the flexion, crossed extension, extensor thrust, scratch, and tendon jerk reflexes resulting presumably from reduced background inhibition. Although reflex stepping was markedly facilitated by the drug, the most dramatic effect of strychnine was its facilitation of reflex walking. Before strychnine administration this response was absent in six of the eight animals. The six non-walkers

1Supported by Grant MHI2003 from the National Institute of Mental Health. Thanks are expressed to C. M. Haugen and V. T. Kuchar for technical assistance.

627

628 HART

moved about with their front legs and dragged their back legs behind them. Dragging of the back legs evoked weak alternate flexion and extension of the back legs. In the two walking animals the back legs extended, revealing a standing reflex (Fig. 1), and the animals were able to walk for short distances on all four legs (Fig. 2). These animals were frequently observed to stand without lowering the head as a counterweight. During walking the hind quarters often fell sideways or the back legs collapsed when the front legs travelled too fast.

The two animals that exhibited reflex walking prior to strychnine administration greatly improved their ability to walk following administration of the drug. Four of the other animals which were previously incapable of walking were, following strychnine administration, able to rise up on their back legs and take several steps before falling (Fig. 3). A type of rabbit hopping in which both back legs extended simultaneously was frequently observed. The remaining two previous non-walkers tended, under the influ- ence of strychnine, to move about with the front legs too rapidly for the back legs to obtain an upright position, but reflex walking could be observed by gently holding the animal's head and allowing it to walk slowly forward. In all animals the effect of strychnine administration was evident from ex- cessive extensor tone of the front legs, rapid breathing, and general excitability. After the effects of the strychnine had subsided, walking activity of the back legs reverted to that which was characteristic of the subject prior to the drug administration.

In order to rule out the possibility that the reflex walking occurred as a result of a functional regeneration of nerve tissue, or incomplete surgical transections, a second transec-

tion was performed on four of the animals, including the two which demonstrated reflex walking before strychnine ad- ministration. The transection was made in the area just posterior to the initial transection. When these animals were tested for reflexes 7-10 days following the second transection there was no change in the pattern of spinal reflexes and following administration of strychnine, there was the same marked facilitation of reflex walking that had been observed during the first series of tests prior to the second transection.

It is generally accepted that strychnine is a suppressor of postsynaptic inhibition [2]. The facilitation by strychnine of neural activities associated with reflex walking evidently reflects the reduction of tonic intraspinal postsynaptic inhibition which in most spinal dogs appears to be strong enough to prevent the occurrence of reflex walking.

There are other studies suggesting the existence of intraspinal tonic inhibitory systems. The Schiff-Sherrington phenomenon [6] has been explained on the basis of the surgical release of tonic inhibitory influences from lower spinal cord to neural dements controlling extensor muscles of the forelimbs. Recurrent facilitation of motor neurons has been shown to be due to disinhibition, a phenomenon requiring the existence of tonic inhibition [12, 13]. Evidence in the present study for the existence of tonic inhibition of reflex walking suggests that reflex walking in the intact animal may be integrated into a total locomotor pattern through the process of disinhibition. That is, reflex walking may be brought into function at the appropriate time by suprasegmental inhibition of the neural elements mediating the tonic inhibition at the segmental level. Were it not for the tonic inhibition, reflex walking might be too easily evoked and would interfere with the animal's locomotor coordination.

REFERENCES

1. Creed, R. S., D. Denny-Brown, J. C. Eccles, E. G. T. Liddell and C. S. Sherrington. Reflex Activity of the Spinal Cord, London: Oxford, 1932.

2. Curtis, D. R. The pharmacology of central and peripheral inhibition. Pharmac. Rev. 15: 333-364, 1963.

3. Freeman, L. W. Experimental observations upon axonal regeneration in the transeeted spinal cord of mammals. Clin. Neurosurg. VIII, Prec. Cong. Neurol. Surg. Baltimore: Williams & Wilkins, 1962, pp. 294--319.

4. Hart, B. L. Sexual reflexes and mating behavior in the male dog. J. comp. physioL PsychoL 64: 388-399, 1967.

5. Kellogg, W. N., J. Deese and W. N. Pronko. On the behavior of the lumbo-spinal dog. J. exp. PsychoL 36: 503-511, 1946.

6. Rueh, T. C. Evidence of the non-segmental character of spinal reflexes from an analysis of the cephalad effects of spinal transection (Shiff-Sherrington phenomenon). Am. J. Physiol. 144: 457--467, 1936.

7. Sherrington, C. S. The Integrative Action of the Nervous System. New Haven: Yale University Press, 1947.

8. Sherrington, C. S. Flexion-reflex of the limb, crossed extension- reflex, and reflex stepping and standing. J. PhysioL 40: 28-121, 1910.

9. Shurrager, P. S. Walking in spinal kittens and puppies. In: Regeneration in the Central Nervous System, edited by W. E. Windle. Springfield: Thomas, 1955, pp. 208-218.

10. Shurrager, P. S. and R. A. Dykman. Walking spinal carnivores. J. comp. physiol. Psychol. 44: 252-262, 1951.

11. Ten Cate, J. Quelques observations sur la locomotion des chiens dent la moeUe 6pini~re est sectionn6e transversalement. Archs nderl. Physiol. 24: 476-485, 1940.

12. Wilson, V. J. and P. R. Burgess. Disinhibition in the cat spinal cord. J. Neurophysiol. 25: 392-404, 1962.

13. Wilson, V. J., F. P. J. Diecke and W. H. Talbot. Action of tetanus toxin on conditioning of spinal motoneurons. J. NeurophysioL 23: 659-666, 1960.