THE EFFECTS OF CONVULSANT AGENTS ON PARTIALLY ISOLATED REGIONS OF THE CENTRAL NERVOUS SYSTEM

The effects of removal of one motor cortex, a frontal lobe, or a complete cerebral hemisphere on the action of various convulsant agents were studied in chronic cats and in spinal preparations. In both sets of experiments, previously decentralized neurons responded to smaller quantities of convulsant drugs than did the intact ones, and pentylenetetrazol, camphor, and picrotoxin, as well as strychnine and acetylcholine, evoked greater and more prolonged responses from these neurons when sufficient time was allowed for sensitization due to partial isolation to take place (in the majority of experiments two to eight months).This was ascertained in myographic recordings and in studies of the electrical activity of the anterior horn cells in high spinal cats and white rats, as well as in photographic and statistical analyses of convulsions induced in chronic animals. The latter study revealed that the convulsions were asymmetrical in the operated cats, the muscular contractions being exaggerated and prolonged contralaterally to the cerebral ablation. The median convulsant dose (CD50) of pentylenetetrazol for the control cats was 7.8 mgm./kgm. (95% confidence limits 7.4–8.1) while that for the operated group was 6.8 mgm./kgm. (95% confidence limits 6.3–7.2). The latent period following the injection of pentylenetetrazol was significantly shorter for the operated group than for the control one, and the convulsions lasted longer in the operated cats than in intact animals. The longer duration of convulsions in the operated group depended on a significantly longer tonic and terminal clonic phase of the convulsion. Two patterns of convulsions could be elicited—a clonic and a more severe clonic–tonic–clonic (CTC) one. In the control group clonic convulsions were more frequent at low dosages of pentylenetetrazol while CTC convulsions pre-dominated at high dosages. In the operated group CTC convulsions were prevalent throughout the range of doses used and occurred in a greater percentage of animals than in the control group. Chemically induced convulsions play a prominent part in the study of epilepsy and in the treatment of some mental derangements, and it is felt that this investigation may contribute to the understanding of the mechanism of action of convulsant agents on the nervous system in which abnormal conditions prevail.

THE EFFECTS OF CONVULSANT AGENTS ON PARTIALLY ISOLATED REGIONS OF THE CENTRAL NERVOUS SYSTEM

The effects of removal of one motor cortex, a frontal lobe, or a complete cerebral hemisphere on the action of various convulsant agents were studied in chronic cats and in spinal preparations. In both sets of experiments, previously decentralized neurons responded to smaller quantities of convulsant drugs than did the intact ones, and pentylenetetrazol, camphor, and picrotoxin, as well as strychnine and acetylcholine, evoked greater and more prolonged responses from these neurons when sufficient time was allowed for sensitization due to partial isolation to take place (in the majority of experiments two to eight months).This was ascertained in myographic recordings and in studies of the electrical activity of the anterior horn cells in high spinal cats and white rats, as well as in photographic and statistical analyses of convulsions induced in chronic animals. The latter study revealed that the convulsions were asymmetrical in the operated cats, the muscular contractions being exaggerated and prolonged contralaterally to the cerebral ablation. The median convulsant dose (CD50) of pentylenetetrazol for the control cats was 7.8 mgm./kgm. (95% confidence limits 7.4–8.1) while that for the operated group was 6.8 mgm./kgm. (95% confidence limits 6.3–7.2). The latent period following the injection of pentylenetetrazol was significantly shorter for the operated group than for the control one, and the convulsions lasted longer in the operated cats than in intact animals. The longer duration of convulsions in the operated group depended on a significantly longer tonic and terminal clonic phase of the convulsion. Two patterns of convulsions could be elicited—a clonic and a more severe clonic–tonic–clonic (CTC) one. In the control group clonic convulsions were more frequent at low dosages of pentylenetetrazol while CTC convulsions pre-dominated at high dosages. In the operated group CTC convulsions were prevalent throughout the range of doses used and occurred in a greater percentage of animals than in the control group. Chemically induced convulsions play a prominent part in the study of epilepsy and in the treatment of some mental derangements, and it is felt that this investigation may contribute to the understanding of the mechanism of action of convulsant agents on the nervous system in which abnormal conditions prevail.

Effects of Carbon Dioxide and Oxygen on Properties of Experimental Seizures in Mice

The influence of various concentrations of carbon dioxide and oxygen on the pattern of maximal electroshock seizures (MES), on pentylenetetrazol (Metrazol)-induced seizures, and on recovery time (RT50) from MES has been studied in mice. The major results are summarized as follows: Increasing the concentration of carbon dioxide in 20% oxygen resulted in marked changes in the MES pattern. The duration of the tonic flexor component was increased, and the duration of the tonic extensor component and of the entire tonic phase was decreased; the ratio of flexion to extension was increased markedly. These changes indicate an anticonvulsant effect of carbon dioxide. Carbon dioxide in a concentration of 15.6% protected 50% of mice against a 97% convulsant dose (CD97) of Metrazol. Hypoxia, induced by inhalation of 15 or 10% oxygen, decreased the duration of the tonic flexor component and increased the duration of the tonic extensor component of the MES; the duration of the entire tonic phase was increased; the ratio of flexion to extension was slightly decreased. These changes indicate an excitatory effect of low oxygen concentrations on the brain, under the stated conditions. Hyperoxia, induced by inhalation of 50, 75 or 90% oxygen, in contrast to hypoxia, resulted in effects on MES similar to those produced by inhalation of carbon dioxide. The RT50 was slightly, but not significantly, decreased by hypoxia (15% oxygen), unchanged by hyperoxia (50% oxygen), and markedly increased by an increase in carbon dioxide concentration. Carbon dioxide (5 and 10%) combined with hypoxia (10% oxygen) produced effects on MES pattern and RT50 similar to those produced by carbon dioxide in 20% oxygen.