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

Abstract

Chronic restraint stress for 6h/21d causes hippocampal CA3 apical dendritic retraction, which parallels spatial memory impairments in male rats. Recent research suggests that chronic immobilization stress for 2h/10d induces CA3 dendritic retraction (Vyas et al., 2002) and questions whether CA3 dendritic retraction and spatial memory deficits can be produced sooner than found following 6h/21d 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 6h/21d 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 6h/21d 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.

Distinct Effects of Repeated Restraint Stress on Basolateral Amygdala Neuronal Membrane Properties in Resilient Adolescent and Adult Rats

“…Resilience and vulnerability were defined based on a well-established biological index of stress, adrenal gland weight (Selye, 1936;Bassett and Cairncross, 1975;Dallman, 1984;Ottenweller et al, 1989;Marquez et al, 2004), and cross checked by EPM and body weight. EPM and body weight are both validated measures of effects of repeated stress in vulnerable rats (Willner et al, 1996;Stone and Quartermain, 1997;Caldji et al, 2000;Maslova et al, 2002;Vyas et al, 2002;Marquez et al, 2004;Weiss et al, 2004;McLaughlin et al, 2007;Pohl et al, 2007;Zhang and Rosenkranz, 2012), further validating the subdivision of populations.…”

Assessment of estradiol influence on spatial tasks and hippocampal CA1 spines: Evidence that the duration of hormone deprivation after ovariectomy compromises 17β-estradiol effectiveness in altering CA1 spines

“…Previous research from our lab suggests that the traditional Y-maze task may be more sensitive to detecting changes in spatial memory of male rats relative to female rats (Conrad et al, 1996;Conrad et al, 2003;Kleen et al, 2006;McLaughlin et al, 2005;McLaughlin et al, 2007;Wright and Conrad, 2005;Wright et al, 2006;Wright and Conrad, 2008). Therefore, to make the task more challenging in this study, we modified the procedure to include longer delays (6 and 24 hours) than previously used (4 hours, Conrad et al, 1996;McLaughlin et al, 2007).…”

“…Tasks included variations of the Y-maze (Conrad et al, 1996;McLaughlin et al, 2005;McLaughlin et al, 2007), water maze (Jarrard, 1983;Morris, 1981;Morris et al, 1982), and object placement (Beck and Luine, 2002;Ennaceur et al, 1997). All rats underwent OVX and then started on a two-pulse schedule of 17β-estradiol injections (0, 5, 10µg, s.c.) at 72 and 48 hours prior to behavioral testing.…”

“…All brains were removed and processed at the same time (72 hours following the last injection). The staining procedure was the same as described previously by our lab (Bellani et al, 2006;Conrad et al, 2007;Kleen et al, 2006;McLaughlin et al, 2005;McLaughlin et al, 2007).…”

Evaluation of the protective effects of tocotrienol-rich fraction from palm oil on the dentate gyrus following chronic restraint stress in rats

“…Restraint stress was induced by wrapping individual rats with a soft and flexible plastic mesh secured at the head and tail ends with metal clips as described by McLaughlin et al (2007). This prevented free mobilisation of the rats, but without imposing unnecessary pain.…”