Chronic restraint stress induces anxiety-like behavior and remodeling of dendritic spines in the central nucleus of the amygdala

Abstract

Previous studies have shown that the anxiogenic effects of chronic stress do not correlate with dendritic remodeling in the central nucleus of the amygdala (CeA). We analyzed the effect of chronic restraint stress (CRS; 20 min/day for 14 days), relative to control (CTRL) conditions on anxiety-like behavior in the elevated plus maze (EPM) and the open field tests, and dendritic morphology, dendritic spine density and spine type numbers in pyramidal neurons of the CeA. Reversal of CRS-induced effects was explored in animals allowed a 14-day stress-free recovery after treatments. CRS decreased the frequency and time in the open arms and increased the anxiety index in the EPM, and reduced visits and time in the center of the open field. Morphological assays in these animals revealed no effect of CRS on dendritic complexity in CeA neurons; however, a decrease in dendritic spine density together with decreased and increased amounts of mushroom and thin spines, respectively, was detected. Subsequent to a stress-free recovery, a significant reduction in open arm entries together with an increased anxiety index was detected in CRS-exposed animals; open field parameters did not change significantly. A decreased density of total dendritic spines, in parallel with higher and lower numbers of thin and stubby spines, respectively, was observed in CeA neurons. Results suggest that CRS-induced anxiety-like behavior might be accounted for by a reduction in synaptic connectivity of the CeA. This effect, which is long lasting, could mediate the persisting anxiogenic effects of chronic stress after exposure to it has ended.

Keywords: Anxiety-like behavior; Central nucleus of the amygdala; Chronic restraint stress; Dendritic spines; Neuronal morphology.