Elsevier

Biological Psychiatry

Volume 72, Issue 6, 15 September 2012, Pages 466-475
Biological Psychiatry

Archival Report
Glucocorticoids Protect Against the Delayed Behavioral and Cellular Effects of Acute Stress on the Amygdala

https://doi.org/10.1016/j.biopsych.2012.04.008Get rights and content

Background

A single episode of acute immobilization stress has previously been shown to trigger a delayed onset of anxiety-like behavior and spinogenesis in the basolateral amygdala (BLA) of rats. Spurred on by a seemingly paradoxical observation in which even a modest increase in corticosterone (CORT), caused by a single vehicle injection before stress, could dampen the delayed effects of stress, we hypothesized a protective role for glucocorticoids against stress.

Methods

We tested this hypothesis by analyzing how manipulations in CORT levels modulate delayed increase in anxiety-like behavior of rats on the elevated plus-maze 10 days after acute stress. We also investigated the cellular correlates of different levels of anxiety under different CORT conditions by quantifying spine density on Golgi-stained BLA principal neurons.

Results

CORT in drinking water for 12 hours preceding acute stress prevented delayed increase in anxiety rather than exacerbating it. Conversely, vehicle injection failed to prevent the anxiogenic effect of stress in bilaterally adrenalectomized rats. However, when CORT was restored in adrenalectomized rats by injection, the delayed anxiogenic effect of stress was once again blocked. Finally, high and low anxiety states were accompanied by high and low levels of BLA spine density.

Conclusions

Our findings suggest that the presence of elevated levels of CORT at the time of acute stress confers protection against the delayed enhancing effect of stress on BLA synaptic connectivity and anxiety-like behavior. These observations are consistent with clinical reports on the protective effects of glucocorticoids against the development of posttraumatic symptoms triggered by traumatic stress.

Section snippets

Animals

Male Wistar rats (45–60 days old, 250–300 g) were housed in a 14/10-hour light/dark schedule (lights on at 8 am) with ad libitum access to food and water at the National Centre for Biological Sciences, Bangalore, India. The Institutional Animal Ethics Committee approved all procedures related to animal maintenance and experimentation.

Stress

Rats were subjected to a single, 2-hour episode of acute immobilization stress (1) between 10 am and 12 pm in plastic immobilization bags (with no access to food

Injection of Vehicle Alone Alleviates the Delayed Anxiogenic Effects of Acute Stress

As reported previously (1), a single 2 h episode of immobilization stress (Fig. 1A) leads to enhanced anxiety-like behavior 10 days later on the EPM. This delayed anxiogenic effect was exhibited as a reduction in both time spent (Figure 1B) and number of open-arm entries (Figure S1A in Supplement 1). Surprisingly, a single subcutaneous injection of vehicle (Veh inj) 30 min before the same acute stress (Figure 1A, Veh inj + Stress) reversed the delayed increase in anxiety back to control levels

Discussion

While earlier studies on the effects of stress on the brain were largely focused on the hippocampus, more recently developed animal models of PTSD have investigated other brain regions (6, 33, 34), and the literature has been extensively reviewed (5, 35). This study was motivated by clinical observations on two facets of PTSD—one temporal and the other therapeutic. First, although PTSD can be triggered by a single severely stressful event, some components of the affective symptoms persist well

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      Single 2 h immobilization stress increases spinal density in principal neurons of the basolateral amygdala (BLA) 10 days after stress, correlating with an increase in anxiety-like behavior. Corticosterone administration in drinking water before stress prevents this increase in spinal density, especially in the proximal region of the dendrite (Rao et al., 2012). Furthermore, corticosterone administration in drinking water 24 h after stress also prevents the increase in spinal density in primary apical dendrites of BLA principal neurons, accompanied by a lower anxiety-like behavior (Chakraborty et al., 2020).

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