Brain biogenic amines and altered thyroid function.

Evidence has been presented that alterations in thyroidal status produce marked changes in the metabolism of several biogenic amines in developing brain. Neonatal hypothyroidism induced either by ¹³¹I or by an anti-thyroid agent, methimazole, markedly decreased the concentrations of norepinephrine, dopamine and 5-hydroxytryptamine and the activity of their rate-limiting enzymes, tyrosine hydroxylase and tryptophan hydroxylase. However, the levels of 5-hydroxyindoleacetic acid, the chief metabolite of 5-hydroxytryptamine were elevated in several regions of the brain. Whereas thyroid deficiency in early life produced no appreciable change in whole brain monoamine oxidase activity, it was increased in mid brain and decreased in the hypothalamus. Brain acetylcholine levels were significantly elevated and the activity of acetylcholinesterase remained unchanged in rats made hypothyroid at 1 day of age. Delaying thyroidectomy for 20 days after birth produced less appreciable changes in norepinephrine and 5-hydroxytryptamine metabolism. Thyroid deficiency suppressed the ontogenesis of behavioural arousal and spontaneous locomotor activity. The administration of L-triiodothyronine to hypothyroid animals in early life restored the metabolism of various neurohumors virtually to the normal limits. However, when the replacement therapy was postponed until adulthood, L-triiodothyronine failed to produce any restorative effects, suggesting that a critical period exists in early life during which thyroid hormone must be present to permit normal developmental pattern of central amines. Data also have been obtained demonstrating that neonatal hyperthyroidism induced by daily administration of L-triiodothyronine results in an increased turnover of norepinephrine and 5-hydroxytryptamine. These amine changes were accompanied by a marked rise in the spontaneous locomotor activity in hyperthyroid rats. Finally, chronic treatment with lithium, an antimanic drug, also known to suppress thyroid hormone production, significantly decreased not only the spontaneous locomotor activity, but also changes in the turnover of 5-hydroxytryptamine and norepinephrine in neonatally hyperthyroid rats.