EFFECT OF THYROXINE AND TRIIDOTHYRONINE ON BRAIN FUNCTION AND ELECTROLYTE DISTRIBUTION IN INTACT AND ADRENALECTOMIZED RATS

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

The effects of thyroxine and triiodothyronine on brain function and on water and electrolyte metabolism were studied in intact and adrenalectomized rats. The most important results can be listed as follows:

1. In intact rats, thyroxine and triiodothyronine increase brain excitability, as measured by the threshold for minimal electroshock seizures, enhance the capacity of brain to sustain maximal (tonic-clonic) electroshock seizures, and slightly accelerate the recovery from such maximal seizures. The relative stimulatony potency of thyroxine and triiodothyronine on brain function is approximately 1 to 5. For both hormones, the stimulatory effect on brain activity is directly related to dose and to duration of treatment.

2. Concomitantly with brain excitability variations, thyroxine and triiodothyronine produce alterations in brain electrolyte metabolism, the most important of which are those concerned with Na distribution (decreased extracellular Na, decreased ratio of extracellular to intracellular Na, increased Na space and increased Na intracellular concentration).

3. In adrenalectomized rats, stimulation of the central nervous system and alterations in brain electrolyte metabolism induced by thyroxine and triiodothyronine are less marked than in intact rats. This suggests that the thyroid hormones stimulate brain function and alter brain electrolyte distribution both by a direct action and through stimulation of the adrenals. There is some indication that, after adrenalectomy, triiodothyronine has a more marked direct effect on the central nervous system than does thyroxine.

4. Administration of adrenocortical extract to adrenalectomized animals receiving thyroxine and triiodothyronine restores to normal the increase in brain excitability and the alterations in electrolyte distribution produced by the two hormones. This is in agreement with previous investigations which show that adrenocortical extract has a "normalizing" effect on brain activity.

5. The effects of thyroxine and triiodothyronine on body weight and temperaturein intact and in adrenalectomized rats are reported and discussed in relation to the effects of the two hormones on brain function and to the role of the adrenal cortex in the response of the central nervous system to thyroid hormone.