THE EFFECT OF HYPERTONIC UREA SOLUTION ON ELECTROSHOCK SEIZURE THRESHOLD AND ELECTROLYTE DISTRIBUTION IN RATS

¹ Department of Pharmacology, University of Utah College of Medicine, Salt Lake City, Utah

The effect of i.p. hypertonic urea solution on brain excitability, as measured by the electroshock seizure threshold (EST), and water and electrolyte content of brain and muscle was investigated in mature rats.

The EST was measured at periods from 15 minutes to 8 hours after treatment with urea or isotonic NaCl solution. The treatment was repeated at weekly intervals for as long as 5 weeks. Following the administration of urea or NaCl in the 6th week, the animals were sacrificed and Na, K, Cl, and water content of brain, skeletal muscle, and plasma were determined.

Hypertonic urea solution produced a prompt fall in water content in brain and muscle, a fall in Na and Cl and a rise in K in muscle, and a rise in Na, Cl, and K in brain. The change in brain electrolytes and water content was maximal in 15 to 30 minutes and the values returned to control levels in 2 hours. EST, which increased about 10%, was maximal at 2 hours and required 4 to 6 hours to return to control values. Water, practically free of electrolyte, was lost from the brain and there was a loss of water accompanied by Na and Cl from muscle. It is suggested that the change in EST is due to a shift in electrolytes and or water between the intracellular and extracellular compartments of the brain, rather than to brain dehydration per se. The relation of these results to the use of hypertonic urea solution in the treatment of status epilepticus in man is briefly discussed.