Odor Cues Released by Ehrlich Tumor-Bearing Mice Are Aversive and Induce Psychological Stress

Abstract

Background/Aims: This study aimed to verify if odor cues released by Ehrlich tumor-bearing mice are aversive and stressful. Methods: Female mice were divided into a control group and an experimental group. One animal of each experimental pair of mice was inoculated with 5 × 10⁶ Ehrlich tumor cells intraperitoneally; the other animal was kept undisturbed and was referred to as a CSP (companion of sick partner). One mouse of each control pair was treated intraperitoneally with 0.9% NaCl (1 mg/kg); the other animal (CHP, companion of healthy partner) was kept undisturbed. Results: It was shown that, in relation to CHP, CSP mice (1) spent less time within the companion zone in a T-maze place preference test, (2) had increased levels of social interaction, (3) had increased levels of plasmatic adrenaline and noradrenaline and (4) displayed no changes in serum corticosterone levels before and after an immobilization stress challenge. It was also shown that (5) cohabitation with 2 tumor-bearing mice was more effective in decreasing neutrophil oxidative burst than cohabitation with 1 sick partner and (6) the presence of a healthy conspecific within the cage of the tumor-injected/CSP pair abrogated the effects of cohabitation on neutrophil activity. These results show that odor cues released by Ehrlich tumor-injected mice are aversive and induce psychological stress. Conclusion: We postulate that the aversive response induced by the chemosignals released by Ehrlich tumor-injected animals activates the sympathetic nervous system and causes the neuroimmunal changes that occur in the mice cohabiting with the sick mice.

Beta-Adrenergic Blockade Decreases the Neuroimmune Changes in Mice Induced by Cohabitation with an Ehrlich Tumor-Bearing Cage Mate

“…As shown in our previous study, odor cues released by the ETB mice are aversive, suggesting that they are stressors for the companion animals [11] . Physical and psychological stressors are known to induce endocrine [12] , neurochemical [13] , and immune [8] changes similar to the changes currently reported in mice after cohabitation with a tumor-bearing cage mate.…”

“…Female mice were chosen based on the results from our previous studies [11,28] and because they are less aggressive than males when housed in groups. The animals were housed under a controlled temperature (22-26 ° C) with artificial light (12-h light/12-h dark, lights on at 7: 00 a.m.) and free access to rodent chow and water.…”

“…Physical and psychological stressors are known to induce endocrine [12] , neurochemical [13] , and immune [8] changes similar to the changes currently reported in mice after cohabitation with a tumor-bearing cage mate. The lack of changes in the serum corticosterone levels in the companions of ETB mice [10,11,14] led us to suggest that the final neural link between the neuroimmune impairments observed in companions of the ETB mice involves catecholamine release and/or CNS catecholaminergic activation as a consequence of the psychological stress imposed by the forced housing condition. Changes in catecholamine levels after stress were reported to modify the cytokine network [15] and cytokines are known to modulate the activity of immune cells [16] and the animal's resistance to diseases [17] .…”

“…Although the overall neuroimmune outcomes of cohabitation in companions of ETB mice have been extensively reported [10,11,14,22,23] , we must determine whether catecholamine release and SNS activation are indeed related to the neuroimmune effects on the development of behavioral and neutrophil alterations reported to be caused by the housing condition. Therefore, the purpose of the present study was to determine the extent to which catecholamines participate in these effects by employing β-AR blocking agents as pharmacological tools.…”

“…Furthermore, we also aimed to analyze the levels and turnover rate of serotonin (5-hydroxytryptamine, 5-HT) in the olfactory bulbs of companions of ETB mice. Olfactory cues released by ETB mice are considered pivotal for the neuroimmune changes induced by cohabitation with ETB mice [11] . Broad spectrum 5-HT receptor agonists attenuate odorevoked olfactory neuron activity in the olfactory bulb [26,27] .…”