PMID- 25623236 OWN - NLM STAT- MEDLINE DCOM- 20150824 LR - 20220316 IS - 1095-6867 (Electronic) IS - 0018-506X (Linking) VI - 69 DP - 2015 Mar TI - The bidirectional effects of hypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats. PG - 106-15 LID - S0018-506X(15)00004-5 [pii] LID - 10.1016/j.yhbeh.2015.01.003 [doi] AB - 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 (15mug/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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Yu, Dafu AU - Yu D AD - School of Life Sciences, Yunnan University, Kunming 650091, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China; Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China. FAU - Zhou, Heng AU - Zhou H AD - School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China. FAU - Yang, Yuan AU - Yang Y AD - School of Life Sciences, Yunnan University, Kunming 650091, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China; Physiological Department, Kunming Medical University, Kunming 650500, China. FAU - Jiang, Yong AU - Jiang Y AD - Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China. FAU - Wang, Tianchao AU - Wang T AD - Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China. FAU - Lv, Liang AU - Lv L AD - Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China. FAU - Zhou, Qixin AU - Zhou Q AD - Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China. FAU - Yang, Yuexiong AU - Yang Y AD - Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China. FAU - Dong, Xuexian AU - Dong X AD - Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China. FAU - He, Jianfeng AU - He J AD - Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China. FAU - Huang, Xiaoyan AU - Huang X AD - State Key Laboratory of Phytochemistry and Plant Resources in Southwest China, and Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201, China. FAU - Chen, Jijun AU - Chen J AD - State Key Laboratory of Phytochemistry and Plant Resources in Southwest China, and Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201, China. FAU - Wu, Kunhua AU - Wu K AD - Department of Nuclear Medicine, First People's Hospital of Yunnan Province, and Key Laboratory of Medical Imaging, Medical Faculty, Kunming University of Science and Technology, Kunming 650032, China. FAU - Xu, Lin AU - Xu L AD - School of Life Sciences, Yunnan University, Kunming 650091, China; School of Life Sciences, University of Science and Technology of China, Hefei, 230026, China; Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China. Electronic address: lxu@vip.163.com. FAU - Mao, Rongrong AU - Mao R AD - Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming 650223, China. Electronic address: talktomaomao@163.com. LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150123 PL - United States TA - Horm Behav JT - Hormones and behavior JID - 0217764 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Thyroid Hormones) RN - 333DO1RDJY (Serotonin) SB - IM MH - Animals MH - *Anxiety/blood/physiopathology MH - Behavior, Animal/*physiology MH - Brain/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - *Depression/metabolism/physiopathology MH - Hippocampus/metabolism MH - Hyperthyroidism/metabolism/physiopathology/*psychology MH - Hypothyroidism/metabolism/physiopathology/*psychology MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Serotonin/metabolism MH - Thyroid Hormones/blood OTO - NOTNLM OT - Anxiety OT - Brain-derived neurotrophic factor OT - Depression OT - Hyperthyroidism OT - Hypothyroidism EDAT- 2015/01/28 06:00 MHDA- 2015/08/25 06:00 CRDT- 2015/01/28 06:00 PHST- 2014/09/03 00:00 [received] PHST- 2014/12/24 00:00 [revised] PHST- 2015/01/16 00:00 [accepted] PHST- 2015/01/28 06:00 [entrez] PHST- 2015/01/28 06:00 [pubmed] PHST- 2015/08/25 06:00 [medline] AID - S0018-506X(15)00004-5 [pii] AID - 10.1016/j.yhbeh.2015.01.003 [doi] PST - ppublish SO - Horm Behav. 2015 Mar;69:106-15. doi: 10.1016/j.yhbeh.2015.01.003. Epub 2015 Jan 23.