Effects of hypothyroidism on serotonin 1A receptors in the rat brain.

Abstract

We investigated the effects of hypothyroidism on serotonin 1A receptors in the rat brain in vivo. Five surgically thyroidectomized male Sprague-Dawley (SD) rats and five hypophysectomized SD rats were used as animal models of hypothyroidism; the same number of sham-operated SD rats served as age-matched controls. After hypothyroidism was confirmed by thyroid function tests, serotonin positron emission tomography (PET) was performed for 120min. All PET data were spatially normalized to T2-weighted magnetic resonance imaging templates; then, time-activity curves of the hippocampus, septum, and cerebellum were extracted using predefined volume-of-interest templates. Non-displaceable binding values in the hippocampus and septum were calculated using a multilinear reference tissue model and parametric maps were constructed. Both volume-of-interest and voxel-based analyses showed higher brain uptake in the thyroidectomized and hypophysectomized rats compared to the respective sham-operated rats. Time-activity curves showed that the brain uptake values for the thyroidectomized and hypophysectomized groups were 21-52% higher than were those in the respective control groups. In the thyroidectomized group, the binding potential values for the hippocampus and septum were 20-26% higher than were those in the sham-thyroidectomized group. In the hypophysectomized group, the binding value for the hippocampus was 23% higher than was that in the sham-hypophysectomized group, whereas the septal binding was not significantly different from that in the sham-hypophysectomized group. Parametric maps for the hypothyroidism also showed significantly higher binding values than did those for the controls. Our results demonstrate that hypothyroidism elevates serotonin 1A receptor binding in the limbic system.