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

Abstract

PURPOSE: We investigated the effects of hypothyroidism on serotonin 1A receptors in the rat brain in vivo. METHODS: 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 120 min. 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. RESULTS: 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. CONCLUSION: Our results demonstrate that hypothyroidism elevates serotonin 1A receptor binding in the limbic system.