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Open Access Publications from the University of California

The Biological Cost of Repeated and Multiple Stress in the Growing Mouse


Stress results in a cost to normal biological fimction (e.g. growth). This cost may be related to a shifting of energy from normal biological function to defense activities, accounting for the impairment of energy sensitive functions such as growth. While the effects of multiple stressors, by themselves, may not alter normal biological function to an appreciable degree, summation of the individual effects may result in a total effect that significantly impairs biological function. This hypothesis was addressed by examining in male C57BV6 mice the biological cost of repeated behavioral stress (4 h restraint, once/day for 7 days) and repeated behavioral stress, combined with immunological stress (LPS injection, i.p. @ µg/g). Additionally, we investigated the short term (24 h) effect of acute behavioral stress (4 h restraint) and acute behavioral stress, coupled with immunological stress (LPS injection). The biological cost was quantified by determining the effects of these multiple stressors on the animal's capacity for growth (body weight gain) and, to account for the stress-induced alteration in growth, we quantified the partitioning of energy among lean tissue, fat tissue, and heat production. We also examined the effect of multiple stress on circulating concentrations of corticosterone, IGF-I, and IL-1.

This work demonstrated that the summation of repeated behavioral stress significantly (P400%, P300%, P 80%, P<0.05).

The additive cost in growing animals exposed to repeated behavioral stress may have resulted from the reduction in food intake and the repeated elevation of circulating corticosterone. Repeated alterations of circulating IGF-I may have also accounted for the impaired growth and energy deposition following long-term behavioral stress. When repeatedly restrained animals also encountered an immunological challenge, the activation of the immune system and the consequent increase in circulating cytokines, such as IL-1, may have summated with the previously engaged behavioral stress response to bring about greater changes in metabolism, alterations IGF-I, and food intake. Together, the results of the present work support the hypothesis that the effects of repeated or multiple stressors summate to significantly disrupt normal biological function, but results also indicate that the interaction of multiple stressors is complex, and may or may not summate in their overall effect on biological function.

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