Research Report| Volume 64, ISSUE 10, P884-890, November 15, 2008

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Acute Hippocampal Brain-Derived Neurotrophic Factor Restores Motivational and Forced Swim Performance After Corticosterone

  • Shannon L. Gourley
    Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut

    Division of Molecular Psychiatry, Department of Psychiatry, Yale University, New Haven, Connecticut
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  • Drew D. Kiraly
    Division of Molecular Psychiatry, Department of Psychiatry, Yale University, New Haven, Connecticut
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  • Jessica L. Howell
    Division of Molecular Psychiatry, Department of Psychiatry, Yale University, New Haven, Connecticut
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  • Peter Olausson
    Division of Molecular Psychiatry, Department of Psychiatry, Yale University, New Haven, Connecticut
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  • Jane R. Taylor
    Address reprint requests to Jane R. Taylor, Ph.D., Yale University, Department of Psychiatry, Division of Molecular Psychiatry, Connecticut Mental Health Center, Ribicoff Labs, 34 Park St., New Haven, CT 06508
    Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut

    Division of Molecular Psychiatry, Department of Psychiatry, Yale University, New Haven, Connecticut

    Department of Psychology, Yale University, New Haven, Connecticut
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      Alterations in cellular survival and plasticity are implicated in the neurobiology of depression, based primarily on the characterization of antidepressant efficacy in naïve rodents rather than on models that capture the debilitating and protracted feelings of anhedonia and loss of motivation that are core features of depression.


      In adult male mice, we evaluated persistent effects of oral corticosterone (CORT) exposure on anhedonic-like behavior, immobility in the forced swim test (FST), motivational performance in the progressive ratio task, and later endogenous CORT secretion. After verifying long-term decreases in hippocampal brain-derived neurotrophic factor (BDNF) and cAMP Response Element Binding protein phosphorylation (pCREB), the ability of direct hippocampal BDNF microinfusion after CORT exposure to reverse deficits was investigated.


      Prior CORT exposure decreased sucrose consumption, appetitive responding, and FST mobility without long-term effects on water/quinine discrimination and endogenous CORT secretion. Critically, BDNF replacement mimicked chronic antidepressant treatment (ADT) by reversing CORT-induced reductions in instrumental performance and FST mobility.


      Together these findings link persistent alterations in hippocampal BDNF expression and CREB transcriptional activity with a persistent depressive-like state—as opposed to ADT efficacy. These results identify hippocampal BDNF as an essential molecular substrate that bidirectionally regulates appetitive instrumental behavior. Additionally, we suggest this CORT model might provide a powerful tool for future investigation into the neurobiology of complex stress-associated depressive symptoms that persist long after stress exposure itself.

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