The use of a short-lasting restraint stressor to investigate the role of the immune system in stressor-induced anxiety-like behavior in male and female mice

Abstract

Exposure to stressful stimuli exacerbates anxiety-like behavior in male mice through immune-mediated events. However, whether this also occurs in females is not yet known. Male and female C57BL/6 mice were exposed to restraint stress (RST) for either 2 h or 8 h per day for 7 days. Anxiety-like behaviors were evaluated immediately following RST using the Marble Burying test (after the 6th day of RST) or the Step Down and Open Field tests (after the 7th day of RST). Blood, colons, spleens, and brains were then collected to assess cytokine levels. Exposure to either 2 h or 8 h of RST significantly increased the number of marbles buried by male and female mice (p = 0.01), but did not significantly affect behavior on the Step Down or the Open Field tests. Exposure to 2 h, but not 8 h, of RST increased IL-1β levels in the colon, and also increased IL-1β levels in the blood of female, but not in male mice. IL-1 β mRNA was significantly increased in the hippocampus (p = 0.009) of males and females exposed to 2 h of RST, but was not different in the spleens of stressor-exposed mice. These data indicate that 2 h of RST may be useful in determining whether stressor-induced immune system activity leads to anxiety-like behavior in both male and female mice.