Abstract
BackgroundLaboratory routine procedures such as handling, injection, gavage or transportation are stressful events which may influence physiological parameters of laboratory animals and may interfere with the interpretation of the experimental results. Here, we investigated if female BALB/c mice derived from in-house breeding and BALB/c mice from a vendor which were shipped during their juvenile life differ in their HPA axis activity and stress responsiveness in adulthood.ResultsWe show that already transferring the home cage to another room is a stressful event which causes an increased HPA axis activation for at least 24 hours as well as a loss of circulating lymphocytes which normalizes during a few days after transportation. However and important for the interpretation of experimental data, commercially available strain-, age- and gender-matched animals that were shipped over-night showed elevated glucocorticoid levels for up to three weeks after shipment, indicating a heightened HPA axis activation and they gained less body weight during adolescence. Four weeks after shipment, these vendor-derived mice showed increased corticosterone levels at 45-min after intraperitoneal ACTH challenge but, unexpectedly, no acute stress-induced glucocorticoid release. Surprisingly, activation of monoaminergic pathways were identified to inhibit the central nervous HPA axis activation in the vendor-derived, shipped animals since depletion of monoamines by reserpine treatment could restore the stress-induced HPA axis response during acute stress.ConclusionsIn-house bred and vendor-derived BALB/c mice show a different stress-induced HPA axis response in adulthood which seems to be associated with different central monoaminergic pathway activity. The stress of shipment itself and/or differences in raising conditions, therefore, can cause the development of different stress response phenotypes which needs to be taken into account when interpreting experimental data.
Highlights
Laboratory routine procedures such as handling, injection, gavage or transportation are stressful events which may influence physiological parameters of laboratory animals and may interfere with the interpretation of the experimental results
This is induced by hypothalamic stimulatory factors such as corticotropin releasing factor (CRF) or vasopressin which are released from axon terminals of CRF neurons originating in the parvocellular part of the paraventricular nucleus of the hypothalamus
We recently showed that BALB/c mice are highly stress sensitive compared with CBA mice [24] and show less stressinduced disturbances compares with C57BL/6 mice after repeated combined acoustic and restraint stress
Summary
Laboratory routine procedures such as handling, injection, gavage or transportation are stressful events which may influence physiological parameters of laboratory animals and may interfere with the interpretation of the experimental results. We investigated if female BALB/c mice derived from in-house breeding and BALB/c mice from a vendor which were shipped during their juvenile life differ in their HPA axis activity and stress responsiveness in adulthood Laboratory animals such as mice and rats are bred under standardized conditions which are very different from their conspecifics in biological environments. Stress hormones are well known modulators of the immune system [14,15,16,17,18] and induce metabolic alterations such as increased glycogenolysis and gluconeogenesis as well as accelerated lipolysis, shift metabolic functions towards carbohydrate, lipid and protein catabolism [19,20,21,22,23] Acute stress activates both the sympathetic nervous system and the HPA axis. After the termination of an acute stress exposure the neuroendocrine systems progressively return to pre-stress levels within 2472 hours
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