ELECTROCONVULSIVE RESPONSES OF RATS TO CONVULSANT AND ANTICONVULSANT DRUGS DURING HIGHALTITUDE ACCLIMATIZATION

¹ Department of Physiology, University of California, Berkeley, California

Three groups of adult, male Long-Evans rats were studied. One group (the controls) was maintained at sea level on the Berkeley campus. The other two were taken to the Barcroft Laboratory of the White Mountain Research Station, at 12,470 feet (3,800 m), where they were kept for 3 and 42 days, respectively. Each group was further subdivided into several subgroups: rats of one subgroup did not receive any drug, and served as untreated controls; the animals of the other subgroups were injected subcutaneously with graded doses of convulsants (strychnine and pentylenetetrazol) and anticonvulsants (acetazoleamide and diphenylhydantoin). The drugs were administered in a single injection, with the exception of diphenylhydantoin which was administered once daily for 4 or 7 days. Durations of phases of maximal electroshock seizures and of postseizure depression, and ED50 for convulsant and anticonvulsant actions were compared before and after drug injections at sea level and at altitude.

A significant increase in convulsability, as quantified by shortened tonic flexion, increased incidence and duration of tonic extension and lowered ED50, for convulsants, and increased ED50 for one of the anticonvulsants (acetazoleamide), was observed in animals at altitude. The increased convulsability was accompanied by a longer postseizure depression in the altitude-acclimatized rats than in the sea-level controls.

Most physiological (sex, age, body weight) and environmental (temperature, nutrition, housing, etc.) variables were well controlled; therefore changes in convulsability and in CNS sensitivity to excitatory and depressant drugs at high altitude may be attributed to conditions of hypoxia and/or hypocapnia and emphasize the necessity of readjusting dosage under different environmental conditions. It is postulated that the increased convulsability at altitude can be related to depression of the inhibitory action of the higher CNS centers on the lower centers. Differences in the magnitude of convulsant and anticonvulsant effects at sea level and at altitude could also be ascribed to differences in circulating levels of the drugs due to changes in detoxifying and excretory rates.