The effect of thyroid hormone on serotonergic neurones: Depletion of serotonin in discrete brain areas of developing hypothyroid rats

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Abstract
A single intraperitoneal injection of 131I in a dose of 200 μCi in 1-day-old rats induced hypothyroidism and decreased the activity of tryptophan hydroxylase in mid-brain region. The levels of 5-hydroxytryptamine also were reduced in cerebellum, mid-brain and striatum by 22%, 29% and 31%, respectively. By contrast, the levels of its metabolite, 5-hydroxyindoleacetic acid, were significantly increased in cerebellum, mid-brain and striatal region. To ascertain whether changes induced by neonatal radiothyroidectomy were specific, the effect of replacement thyroid hormone therapy was studied on 5-hydroxytryptamine metabolism. Daily administration of l-triiodothyronine (10 μg/100 g s.c.) for 25 days beginning from five days after radio-iodine treatment enhanced tryptophan hydroxylase activity, tryptophan and 5-hydroxytryptamine levels to values seen in normal rats of the corresponding age group. The concentration of 5-hydroxyindoleacetic acid decreased following l-triiodothyronine treatment. Furthermore, when replacement therapy with l-triiodothyronine was postponed until adulthood, no significant effects could be seen on various parameters related to 5-hydroxytryptamine metabolism. Our data demonstrate that deficiency of thyroid hormone in early life disrupts the normal upsurge of 5-hydroxytryptamine metabolism in brain. A critical period exists in early life of rats during which thyroid hormone must be present for the optimal development of 5-hydroxytryptamine metabolizing systems in maturing brain.