Sex differences and phase of light cycle modify chronic stress effects on anxiety and depressive-like behavior.

The experiment examined whether sex differences and the phase of the light cycle modified how chronic restraint stress influenced anxiety and depressive-like behavior. Rats were restrained (6h/d/21d) and tested on the open field (OF), elevated plus maze (EPM), forced swim test (FST), and sucrose preference (SP) test. Chronic stress increased anxiety in both males and females in different tasks during the dark phase, but not in the light phase. When tested during the dark, chronic stress decreased time and grid crossings in the center arena of the OF in males, whereas chronic stress decreased open arm entries and time in the EPM in females. For OF and EPM, an anxiety index calculation confirmed that chronic stress increased anxiety measures when taking into consideration locomotion metrics. For the FST and SP, chronic stress had a tendency to alter the immobility index and sucrose preference in both sexes, but did not reach statistical significance alone. Therefore, a separate z-score was computed for each task and summed to represent a combined z-score of depressive-like behavior. In the light phase, chronic stress increased depressive-like behavior in males, but decreased depressive-like behavior in females. Chronic stress had no statistically significant effects on depressive-like behavior in the dark phase, although the pattern of chronic stress effects on depressive-like behavior in females was similar for both light cycle phases. The results indicate that chronic restraint stress effects on anxiety and depressive-like behavior depend upon the type of task, phase of the light cycle and sex of the individual.