EFFECT OF VARIATIONS IN EXTRACELLULAR SODIUM CONCENTRATION ON THE SUSCEPTIBILITY OF MICE TO PENTYLENETETRAZOLE (METRAZOL)-INDUCED SEIZURES

¹ Departments of Pharmacology, University of Utah College of Pharmacy and College of Medicine, Salt Lake City, Utah

The convulsant dose (CD₅₀) of intravenously administered pentylenetetrazole (Metrazol) for maximal (tonic-clonic) seizures and of subcutaneously administered Metrazol for minimal (clonic) seizures was determined in normal, acutely hyponatremic, and acutely hypernatremic mice. In addition, the CD₅₀ of intravenously administered Metrazol for minimal seizures and the convulsant current (CC₅₀) for minimal electroshock seizures were determined in normal, acutely hyponatremic, and acutely and chronically hypernatremic mice; the concentration of plasma sodium was also determined in these experiments. The results obtained were analyzed for the influence of the concentration of extracellular sodium on the susceptibility of mice to the convulsant effects of Metrazol and electroshock. The results obtained may be summarized as follows:

1. Acute hyponatremia, induced by the intraperitoneal injection of isosmolar glucose solution, and acute hypernatremia, induced by the intravenous injection of 20 per cent sodium chloride solution, had no significant effect either on the intravenous Metrazol CD₅₀ for maximal seizures or on the subcutaneous Metrazol CD₅₀ for minimal seizures.

2. Acute hyponairemia (plasma sodium reduced by 11.8 per cent) decreased the CC₅₀ for minimal electroshock seizures by 37.0 per cent and decreased the intravenous Metrazol CD₅₀ for minimal seizures by 32.0 per cent. Thus, hypollatrelflia increases the susceptibility of mice to Metrazol-induced seizures approximately to the same extent as to electroshock-induced seizures. Reasons are presented for the inability to demonstrate the hyponatremia-induced increase in susceptibility to Metrazol unless appropriate testing methods are employed.

3. Acute hypernatremia (plasma sodium increased by 3.3 to 9.2 per cent) increased the CC₅₀ for minimal electroshock seizures by approximately 28 per cent. In contrast., this procedure decreased the intravenous Metrazol CD₅₀ for minimal seizures by approximately 12 per cent, but the decrease was not statistically significant. Thus, acute hypernatremia decreases susceptibility of mice to electroshock-induced seizures and tends to increase susceptibility to Metrazolinduced seizures.

4. Chronic hypernatremia (plasma sodium increased by 10.5 per cent), induced by 8 days of treatment with desoxycorticosterone acetate, increased the CC₅₀ for minimal electroshock seizures by 30 per cent. In marked contrast, this procedure decreased the intravenous Metrazol CD,₅₀ for minimal seizures by 21 per cent. Thus, chronic hypernatremia significantly decreases susceptibility to electroshock-induced seizures and significantly increases susceptibility to Metrazol.

It is concluded that hyponatremia in mice increases susceptibility to both electroshock and Metrazol seizures, and that hypernatremia decreases susceptibility to electroshock seizures but enhances susceptibility to Metrazol seizures. The suggestion is made that the hypernatremia-induced increase in susceptibility to Metrazol may be due to an effect of the convulsant drug on the "sodium pump" mechanism of brain cells, thereby to lower the brain Na ratio.