Wheel running and fluoxetine antidepressant treatment have differential effects in the hippocampus and the spinal cord

Neuroscience. 2007 Feb 9;144(3):1033-44. doi: 10.1016/j.neuroscience.2006.10.016. Epub 2006 Nov 28.


Exercise and antidepressants used independently have been shown to increase hippocampal brain-derived neurotrophic factor (BDNF) and neurogenesis. Despite the fact that patients with depression are often prescribed both, the effects of the exercise and fluoxetine antidepressant treatment used in combination are unknown. Using C57Bl/10 female mice, BDNF protein, insulin-like growth factor 1 (IGF-1) protein and neurogenesis were measured in the hippocampus after 21 days of wheel running, 21 days of fluoxetine antidepressant therapy (daily i.p. injections of 5 mg/kg, 10 mg/kg or 25 mg/kg) and the combination of the two. BDNF protein and cytogenesis/neurogenesis increased in the hippocampus with fluoxetine (high dose), but not wheel running. Hippocampal IGF-1 protein did not change with either treatment. There were no synergistic effects of combining exercise and fluoxetine treatment. Recent reports have also shown that exercise induces molecular mechanisms that benefit the spinal cord and can improve recovery after spinal cord injury (SCI); therefore, we repeated the assays in the spinal cord. Results showed that BDNF, IGF-1 and neurogenesis behave independently in the hippocampus and spinal cord. BDNF protein did not change in the spinal cord with either wheel running or fluoxetine treatment. Spinal cord IGF-1 protein did not change with wheel running, but it decreased with fluoxetine (high dose). Furthermore, spinal cord cytogenesis decreased with fluoxetine treatment. The combined wheel running and fluoxetine groups did not show synergistic results. Thus, the hippocampus and the spinal cord respond in distinct ways to wheel running and fluoxetine, and a prior induction of BDNF, IGF-1 or cytogenesis is unlikely to be the mechanism for wheel running providing a margin of protection against SCI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / pharmacology
  • Brain-Derived Neurotrophic Factor / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Count
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Proliferation / drug effects
  • Depressive Disorder / metabolism
  • Depressive Disorder / physiopathology
  • Depressive Disorder / therapy*
  • Dose-Response Relationship, Drug
  • Exercise Therapy / methods*
  • Female
  • Fluoxetine / pharmacology*
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Physical Conditioning, Animal / physiology*
  • Spinal Cord / cytology
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism
  • Stem Cells / drug effects
  • Stem Cells / metabolism


  • Antidepressive Agents, Second-Generation
  • Brain-Derived Neurotrophic Factor
  • Fluoxetine
  • Insulin-Like Growth Factor I