1. The effect of the age at which thyroidectomy is performed and replacement therapy begun has been studied in the rat using the Hebb-Williams closed field test to measure cerebral capacity.
2. Rats thyroidectomized at birth, either by giving 131I or by the chronic administration of methyl thiouracil, made significantly more errors than did normal litter-mates. The degree of impairment was progressively reduced when thyroidectomy was delayed, and the behaviour of rats thyroidectomized on the 25th day of age proved indistinguishable from that of the euthyroid individual.
3. Replacement therapy with triiodothyronine was completely successful in neonatally thyroidectomized rats when begun by the 10th day of age, but unsuccessful if delayed until the 24th day.
4. Qualitative changes in behaviour were observed as a result of thyroidectomy at birth but tended to disappear when thyroidectomy was delayed or when therapy was started early. These included a more rapid rate of habituation and an increased tendency to perseverate. There was also some evidence of a difference between normal and thyroidectomized animals in the mode of solution of the several problems presented.
5. The reported experimental findings reinforce the view that thyroid hormone is a potent factor regulating cerebral development during a critical period of life, and that in its absence developmental abnormalities arise which are as yet ill-defined but cannot be reversed by subsequent replacement therapy.
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