Ginkgolide-Platinum(II) Complex GPt(II) Exhibits Therapeutic Effect on Depression in Mice via Upregulation of DA and 5-HT Neurotransmitters

BACKGROUND: Depression is the 5(th) most prevalent disorder adversely affecting the health of humans worldwide. The present study evaluated the antidepressant effect of ginkgolide-platinum(II) complex in vivo in a mice model of CMS-induced depression. MATERIAL/METHODS: Depression was induced in mice by social isolation followed by chronic mild stress. After stress, the mice were assigned randomly to a model group, a 3 mg/kg group, a 6 mg/kg group, and a 12 mg/kg group. The mice in the 3 treatment groups were intraperitoneally injected with a single dose of 3.0, 6.0, or 12.0 mg/kg GPt(II) on day 11 of stress. The behavioral changes in mice were analyzed on day 21 of GPt(II) treatment by suspension and open field tests. RESULTS: The GPt(II) treatment significantly increased the numbers of crossings and rearings in CMS mice. Treatment of mice with GPt(II) significantly elevated dopamine, BDNF, and serotonin levels in hippocampus tissues. The CMS-mediated reduction of neuropeptide production in the hippocampus tissues was significantly alleviated by GPt(II) treatment (P<0.05). The GPt(II) treatment suppressed the effect on CMS-induced elevated level of MAO-A in hippocampus tissues. Treatment with GPt(II) significantly repressed caspase-3 activation induced by CMS in the hippocampus tissues of mice. The GPt(II) treatment significantly (P<0.05) upregulated Hsp70 mRNA level in depression model mice. The levels of dopamine, serotonin, and BDNF were increased from 187.83±8.53, 289.65±10.76, and 7.98±1.87 ng/g, respectively, in the model group to 657.63±24.47, 720.54±28.09, and 22.56±3.11 ng/g, respectively, in the 12 mg/kg GPt(II) treatment group. CONCLUSIONS: GPt(II) treatment significantly relieved characteristics of depression in the mice through upregulation of neurotransmitter, neuropeptide, and Hsp70 expression. Moreover, GPt(II) downregulated monoamine oxidase-A levels in the mouse hippocampus tissues. Therefore, further research is warranted on the possible therapeutic effect of GPt(II) in the treatment of depression.