Synergetic effects of quetiapine and venlafaxine in preventing the chronic restraint stress-induced decrease in cell proliferation and BDNF expression in rat hippocampus

Authors

  • Haiyun Xu,

    1. Neuropsychiatry Research Unit, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Canada
    2. Laboratory of Neuropharmacology, School of Pharmaceutical Science, Wenzhou Medical College, Zhenjiang, China
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  • Zhong Chen,

    1. Neuropsychiatry Research Unit, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Canada
    2. Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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  • Jue He,

    1. Neuropsychiatry Research Unit, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Canada
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  • Samson Haimanot,

    1. Neuropsychiatry Research Unit, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Canada
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  • Xiaokun Li,

    1. Laboratory of Neuropharmacology, School of Pharmaceutical Science, Wenzhou Medical College, Zhenjiang, China
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  • Lillian Dyck,

    1. Neuropsychiatry Research Unit, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Canada
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  • Xin-Min Li

    Corresponding author
    1. Neuropsychiatry Research Unit, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Canada
    2. Laboratory of Neuropharmacology, School of Pharmaceutical Science, Wenzhou Medical College, Zhenjiang, China
    • Neuropsychiatry Research Unit, 103 Wiggins Road, Saskatoon, S7N 5E4 Canada
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Abstract

Clinical studies show better response rates of patients with depression and schizophrenia to combinations of atypical antipsychotics and antidepressants, compared to responses to either type of drugs alone. Animal studies demonstrate that some antipsychotics and antidepressants increase neurogenesis and BDNF expression in the hippocampus, which is reduced in volume in patients with depression or schizophrenia. We hypothesized that the better therapeutic effects of combined treatment seen in schizophrenia and depression patients are related to the additive or synergistic effects of combined treatment on hippocampal neurogenesis and BDNF expression. To test this hypothesis, we investigated the effects of chronic administration of quetiapine, venlafaxine, and their combination, on hippocampal cell proliferation and BDNF expression in rats, when subjected to chronic restraint stress (CRS) during the last 2 weeks of a 3-week drug administration period. We found (1) CRS decreased hippocampal cell proliferation and BDNF expression; (2) chronic administration of quetiapine or venlafaxine dose-dependently prevented these decreases in hippocampal cell proliferation and BDNF expression caused by CRS (6 h/day for 14days); (3) the combination of lower doses of quetiapine (5mg/kg) and venlafaxine (2.5mg/kg) increased hippocampal cell proliferation and prevented BDNF decrease in stressed rats, whereas each of the drugs exerted mild or no effects; (4) individual higher doses of quetiapine (10mg/kg) or venlafaxine (5mg/kg) exerted effects comparable to those produced by their combination. These results support our hypothesis and can lead to future studies to develop new therapeutic approaches for treatment-resistant depression and the negative symptoms of schizophrenia. © 2006 Wiley-Liss, Inc.

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