Correlation Between Serotonin 2A Receptor Function And Hypothyroidism With Depression-like Behavior

Objective:To observe the behavioral changes of hypothyroid rats and analyze the expression of 5-HT_2A（serotonin type 2A）receptor in the prefrontal cortex and hippocampus of hypothyroid rats and to explore the correlation between the exp-ression of 5-HT_2Areceptor and the rats’depression-like behavior.Materials and Methods:Twenty healthy adult male SD（Sprague Dawley）rats（about 8 weeks of age）were randomly divided into two groups:the control group and the hypothyroid group,with 10 rats each.Animals were housed on a 12h/12h light/dark cycle,with lights on from 8AM to 8PM daily.All animals were acclimatizedto the experimental environment for 1 week before the test.During treatment period,rats in the hypothyroid group were given 0.05%PTU（Propylthiouracil）dissolved in water for 5 weeks,while rats in the control group were given the same am-ount of water,and all rats were randomly fed with laboratories’food.We measu-red the rats’body weightonce a week and evaluate the behaviors of rats through OFT（Open-field Test）,FST（Forced Swimming Test）and TST（Tail Suspen-sion Test）.The rats’serum TT₃（Total Triiodothyronine）and TT₄（Total thyroxine）concerntrations were measured by radioimmunoassay from the blood of anestheti zed rats through the angular vein in the end of the behavioral tests.Then the ra ts’brains were taken out by Cardiac-perfusion and the expression of 5-HT_2Arece-ptor in prefrontal cortex and hippocampus was measured by immunohistochemis-try and Western blot.The descriptive data of the two groups were compared with Paired t-test,Pearson’s correlation coefficient was used for the estimation of the correlation between the behavioral tests and the expression of 5-HT_2Arece-ptor in prefrontal cortex and hippocampus.Results:The serum TT₃and TT₄ concentrations（ng/ml）in the hypothyroid group were significantly lower than those in the control group（t=3.420,P=0.0076;t=8.981,P<0.0001）,and their body weight decreased significantly（t=8.341,P=0.0004）.There were no significant differences between the two groups（t=0.4432,P=0.8021;t=0.1301,P=1.666;t=1.939,P=0.0845）in any parameter in the OFT,while the immobility time of the hypothyroid rats during the FST（t=3.307,P=0.0091）and TST（t=5.522,P=0.0004）increased signifiacantly as compared with the control group.The expression of 5-HT_2Areceptor in the prefrontal cortex and hippocampus of the hypothyroid group was significantly lower than that of the control group（t=5.248,P=0.0005;t=5.536,P=0.0004）,and the expression of 5-HT_2Areceptor protein in the prefrontal cortex and hippocampus of hypothyroid rats revealed the same result（P=0.001;P=0.040）.The expression of 5-HT_2Areceptor in prefrontal cortex and hippocampus was negatively correlated with the immobility time of FST（r=-0.5162,P=0.0198;r=-0.6075,P=0.0045）and TST（r=0.7650,P<0.0001;r=-0.6739,P=0.0011）significantly.Conclusions:Hypothyroidism can cause weight loss and depression-like behavior in rats,which is mainly manifested by increased immobility time in FST and TST.The expression of 5-HT_2Areceptor in the prefrontal cortex and hippocampus was reduced in hypothyroid rats with depression-like behavior.And the expression of5-HT_2Areceptor protein also decreased in the same brain region.The expression of 5-HT_2Areceptor was correlated with the immobility time of rats in FST and TST.The depression-like behavior of hypothyroid rats may be closely related to the abnormal function of 5-HT_2Areceptor in prefrontal cortex and hippocampus.