Bulbospinal serotonergic activity during changes in thyroid status

A three-part study explored the basis for an interaction between changes in thyroid status and bulbospinal serotonin (5HT) metabolism. In experiment 1, three well-characterized models of primary hypothyroidism were all accompanied by significant increases in 5HT metabolism. In experiment 2, circulating thyroid hormone levels were experimentally varied from very low methimazole (Meth) treatment to very high (T3 implants: 2.5, 5.0, or 7.5 mg triiodothyronine). As in experiment 1, Meth led to elevated 5HT. Hyperthyroidism was accompanied by significant reductions in 5HT, while urinary norepinephrine excretion paralleled 5HT. In experiment 3, rats were subjected to Meth either 2 weeks before or after induction of diabetes with streptozotocin (Stz). Meth prevented Stz-associated reductions in 5HT and attenuated development of hyperphagia. Meth could not reverse established Stz-associated reduction in 5HT or hyperphagia, although both were slightly attenuated. Thus, although the first two experiments argue for a simple inverse relationship between circulating thyroid hormone levels and 5HT in the brain, experiment 3 demonstrated that Stz-associated decrements in 5HT could not be reversed by subsequent lowering of circulating thyroid hormone. Nor did accompanying measurements indicate that glycemic status or circulating levels of leptin were important predictors of 5HT. Thus the interaction between thyroid hormones and 5HT is both more subtle and more complex than previously thought.