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Change of depression-like behavior in chronic alcoholism and withdrawal model,and co-mechanism of depression and chronic alcoholism in mice
Authors:JIANG Xi  TIAN Fu-rong  ZHAO Ying-zheng
Institution:1. Pharmaceutical Preparation Section of Ningbo Mingzhou Hospital, Ningbo 315100, China; 2. Wenzhou Medical University, Wenzhou 325035, China
Abstract:AIM: To investigate the behavior of depression in chronic alcoholism and withdrawal model of mice, and to explore the co-mechanism of alcoholism and depression. METHODS: A novel model of chronic alcoholism was constructed in this study. The animals were divided into normal control group, and alcohol 7 d, 14 d, 21 d and 28 d groups. The mice were given alcohol preference test on the 6th, 13th, 20th and 27th days. After the test, alcohol were withdrawn for 1 d, then the next day the mice were given behavior test of depression. After the test, the mice were sacrificed. The contents of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) were detected by HPLC. The expression of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) was detected by Western blot. RESULTS: The mice showed an obvious drinking phenomenon, and the immobility time of forced swimming test and tail suspension test was significantly increased, with increasing drinking days and withdrawal times. 5-HT level in 7 d group mice only increased in frontal cortex (P < 0.05). However, compared with control group, 5-HT levels in hippocampus and cortex were decreased on the 21th and 28th days (P < 0.01). NE levels in 21 d and 28 d groups were decreased in hippocampus and frontal cortex (P < 0.05), and no significant change was observed in 7 d and 14 d groups. The protein levels of p-CREB and BDNF were significantly decreased in hippocampus and frontal cortex of 12 d and 28 d groups (P < 0.05), and no significant change was observed in 7 d group and 14 d group. CONCLUSION: The co-mechanism of alcoholism, withdrawal and depression is related to 5-HT. 5-HT-cAMP-CREB-BDNF signaling pathway may be a common mechanism for alcoholism and depression.
Keywords:Alcoholism  Depression  5-hydroxytryptamine  cAMP response element-binding protein  Brain-derived neurotrophic factor  
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