The effects of chronic stress on hippocampal morphology and function: an evaluation of chronic restraint paradigms

Brain Res. 2007 Aug 3;1161:56-64. doi: 10.1016/j.brainres.2007.05.042. Epub 2007 Jun 2.


Chronic restraint stress for 6 h/21 days causes hippocampal CA3 apical dendritic retraction, which parallels spatial memory impairments in male rats. Recent research suggests that chronic immobilization stress for 2 h/10 days induces CA3 dendritic retraction [Vyas, A., Mitra, R., Shankaranarayana Rao, B.S., Chattarji, S., 2002. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J. Neurosci. 22, 6810-6818.] and questions whether CA3 dendritic retraction and spatial memory deficits can be produced sooner than found following 6 h/21 days of restraint stress. Therefore, this study investigated the effects of four different durations of chronic restraint stress (varied by hours/day and total number of days) and the subsequent effects on hippocampal CA3 morphology and spatial memory in the same male Sprague-Dawley rats. The results showed that only rats exposed to the 6 h/21 days restraint paradigm exhibited CA3 apical dendritic retraction, consistent spatial memory deficits, and decreased body weight gain compared to experimental counterparts and controls. While chronically stressing a rat with wire mesh restraint has a physical component, it acts primarily as a psychological stressor, and these findings support the interpretation that chronic psychological stress produces hippocampal-dependent cognitive deficits that are consistent with hippocampal structural changes. Differences in stress effects observed across different studies may be due to rat strain, type of stressor, and housing conditions; however, the current findings support the use of chronic restraint stress, with wire mesh, for 6 h/21 days as a reliable and efficient method to produce psychological stress and to cause CA3 dendritic retraction and spatial memory deficits in male Sprague-Dawley rats.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Body Weight / physiology
  • Dendrites / pathology
  • Dendrites / ultrastructure
  • Hippocampus / pathology*
  • Hippocampus / ultrastructure
  • Male
  • Maze Learning / physiology
  • Neurons / pathology
  • Neurons / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Restraint, Physical / methods*
  • Silver Staining / methods
  • Stress, Psychological / etiology*
  • Stress, Psychological / pathology*
  • Time Factors