title: Environmental enrichment induces behavioral recovery and enhanced hippocampal cell proliferation in an antidepressant-resistant animal model for PTSD.
abstract: BACKGROUND
  Post traumatic stress disorder (PTSD) can be considered the result of a failure to recover after a traumatic experience. Here we studied possible protective and therapeutic aspects of environmental enrichment (with and without a running wheel) in Sprague Dawley rats exposed to an inescapable foot shock procedure (IFS).
  
  
  RESULTS
  IFS induced long-lasting contextual and non-contextual anxiety, modeling some aspects of PTSD. Even 10 weeks after IFS the rats showed reduced locomotion in an open field. The antidepressants imipramine and escitalopram did not improve anxiogenic behavior following IFS. Also the histone deacetylase (HDAC) inhibitor sodium butyrate did not alleviate the IFS induced immobility. While environmental enrichment (EE) starting two weeks before IFS did not protect the animals from the behavioral effects of the shocks, exposure to EE either immediately after the shock or one week later induced complete recovery three weeks after IFS. In the next set of experiments a running wheel was added to the EE to enable voluntary exercise (EE/VE). This also led to reduced anxiety. Importantly, this behavioral recovery was not due to a loss of memory for the traumatic experience. The behavioral recovery correlated with an increase in cell proliferation in hippocampus, a decrease in the tissue levels of noradrenalin and increased turnover of 5-HT in prefrontal cortex and hippocampus.
  
  
  CONCLUSIONS
  This animal study shows the importance of (physical) exercise in the treatment of psychiatric diseases, including post-traumatic stress disorder and points out the possible role of EE in studying the mechanism of recovery from anxiety disorders.
authors.affiliation: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. h.hendriksen@uu.nl
authors.forename: Hendrikus
authors.initials: H
authors.lastname: Hendriksen
authors.forename: Jolanda
authors.initials: J
authors.lastname: Prins
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Oosting
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000150:complications; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D049109:Cell Proliferation; D003624:Darkness; D004195:Disease Models, Animal; D004351:Drug Resistance; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010805:Physical Conditioning, Animal; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055500:Resilience, Psychological / Q000187:drug effects; D012769:Shock / Q000150:complications; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D015306:Biogenic Monoamines