Neurochemical and behavioral alterations elicited by a chronic intermittent stressor regimen: implications for...

Although stressors induce a series of adaptive neurochemical changes, sustained physiological activation associated with protracted stressor exposure may engender adverse effects (allostatic load). In the present investigation CD-1 mice exposed to a series of different stressors, twice a day over 54 days, exhibited increased signs of depression and anxiety, including increased passivity in a forced swim test, reduced aggression in a social interaction test, and delayed approach to food in a novel environment. Consistent with the view that a chronic stressor regimen affects immune-related processes, sickness behavior elicited by the proinflammatory cytokine, interleukin-1beta, was augmented in response to a chronic but not an acute stressor. Relative to nonstressed mice, median eminence serotonin was augmented by the cytokine treatment administered 24 h after chronic stressor exposure. Treatment with IL-1beta diminished plasma growth hormone levels and increased circulating corticosterone levels irrespective of the animals stressor history. It is suggested that chronic stressor exposure may instigate relatively protracted neurochemical effects, thereby influencing the behavioral responses to later psychological and systemic challenges.