1. The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats.
- Author
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Yu D, Zhou H, Yang Y, Jiang Y, Wang T, Lv L, Zhou Q, Yang Y, Dong X, He J, Huang X, Chen J, Wu K, Xu L, and Mao R
- Subjects
- Animals, Brain metabolism, Brain-Derived Neurotrophic Factor metabolism, Hippocampus metabolism, Hyperthyroidism metabolism, Hyperthyroidism physiopathology, Hypothyroidism metabolism, Hypothyroidism physiopathology, Male, Rats, Rats, Sprague-Dawley, Serotonin metabolism, Thyroid Hormones blood, Anxiety blood, Anxiety physiopathology, Behavior, Animal physiology, Depression metabolism, Depression physiopathology, Hyperthyroidism psychology, Hypothyroidism psychology
- Abstract
Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using (131)iodine ((131)I) and hyperthyroidism using levothyroxine (LT4). Serum free thyroxine (FT4) and triiodothyronine (FT3) significantly decreased in the hypothyroid of rats with single injections of (131)I (5mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline-vehicle administered rats. LT4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT4 (15μg/kg) caused a greater than 10-fold increase in serum FT4 and FT3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15mg/kg) diminished serum FT4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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