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J Affect Disord. 2016 Jun;197:100-6. doi: 10.1016/j.jad.2016.03.017. Epub 2016 Mar 9.

Zinc and imipramine reverse the depression-like behavior in mice induced by chronic restraint stress.

Author information

1
Department of Naval Hygiene, Second Military Medical University, Shanghai, China.
2
Department of Naval Hygiene, Second Military Medical University, Shanghai, China. Electronic address: huangjlsmmu@126.com.
3
Department of Naval Hygiene, Second Military Medical University, Shanghai, China. Electronic address: shenhuicn@126.com.

Abstract

Depression is a common psychopathological disorders. Studies of depression have indicated that zinc play a role in the depression pathophysiology and treatment. In present study, we examined the effects of zinc and imipramine supplement alone or combination of zinc and imipramine in mice induced by chronic restraint stress (CRS). Moreover, the possible roles of zinc receptor (G protein-coupled receptor 39, GPR39)-related pathway was investigated. Decreased weight and increased corticosterone (CORT) were observed after 3 weeks CRS exposure. It was shown that CRS induced lower serum zinc, higher hippocampal zinc, increased immobility time in tail suspension test and decreased movement distance in spontaneous activity test, which could be normalized by zinc (30 mg/kg) and imipramine (20 mg/kg) supplement alone and combination of zinc (15 mg/kg) and imipramine (5 mg/kg) for 3 weeks after CRS exposure. Moreover, the changes in mRNA expressions of GPR39, cAMP-response element binding protein (CREB), brain-derived neurotropic factor (BDNF) and n-methytl-d-aspartate receptors (NMDAR) could be reversed by the same treatment mentioned above. These results suggested that zinc dyshomeostasis in serum and hippocampus and depression-like behavior in CRS exposure animals observed in present study could be normalized by zinc and imipramine. The combination of zinc and imipramine in low dose has synergetic effects. The possible mechanism might be correlated to GPR39 receptor-related pathway.

KEYWORDS:

Chronic restraint stress; Depression; GPR39; Imipramine; Zinc

PMID:
26985741
DOI:
10.1016/j.jad.2016.03.017
[Indexed for MEDLINE]

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