Sustained running in rats administered corticosterone prevents the development of depressive behaviors and enhances hippocampal neurogenesis and synaptic plasticity without increasing neurotrophic factor levels

Cell Transplant. 2014;23(4-5):481-92. doi: 10.3727/096368914X678490.


We have previously shown that voluntary running acts as an anxiolytic and ameliorates deficits in hippocampal neurogenesis and spatial learning. It also reduces depression-like behaviors that are normally observed in rats that were administered either low (30 mg/kg) or moderate (40 mg/kg) doses of corticosterone (CORT). However, the protective effects of running were absent in rats treated with a high (50 mg/kg) dose of CORT. We examined whether allowing animals to exercise for 2 weeks prior and/or concurrently with the administration of 50 mg/kg CORT treatment could have similar protective effects. We examined hippocampal neurogenesis using immunohistochemical staining of proliferative and survival cells with the thymidine analogs (BrdU, CIdU, and IdU). In addition, we monitored synaptic protein expression and quantified the levels of neurotrophic factors in these animals as well as performing behavioral analyses (forced swim test and sucrose preference test). Our results indicate that the depressive phenotype and reductions in neurogenesis that normally accompany high CORT administration could only be prevented by allowing animals to exercise both prior to and concurrently with the CORT administration period. These animals also showed increases in both synaptophysin and PSD-95 protein levels, but surprisingly, neither brain-derived neurotrophic factor (BDNF) nor insulin-like growth factor 1 (IGF-1) levels were increased in these animals. The results suggest that persistent exercise can strengthen resilience to stress by promoting hippocampal neurogenesis and increasing synaptic protein levels, thereby reducing the deleterious effects of stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Behavior, Animal
  • Brain-Derived Neurotrophic Factor / metabolism
  • Corticosterone / pharmacology*
  • Depressive Disorder / metabolism
  • Depressive Disorder / pathology
  • Disks Large Homolog 4 Protein
  • Hippocampus / cytology
  • Hippocampus / pathology
  • Insulin-Like Growth Factor I / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Membrane Proteins / metabolism
  • Nerve Growth Factors / metabolism*
  • Neurogenesis / drug effects*
  • Neuronal Plasticity / drug effects*
  • Phenotype
  • Physical Conditioning, Animal
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / metabolism
  • Synaptophysin / metabolism


  • Anti-Inflammatory Agents
  • Brain-Derived Neurotrophic Factor
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Growth Factors
  • Synaptophysin
  • Insulin-Like Growth Factor I
  • Corticosterone