Cancer induces inflammation and depressive-like behavior in the mouse: modulation by social housing - PubMed (original) (raw)

Cancer induces inflammation and depressive-like behavior in the mouse: modulation by social housing

Donald M Lamkin et al. Brain Behav Immun. 2011 Mar.

Abstract

Considerable data demonstrate a high prevalence of depressive symptoms in cancer patients. This study introduces an experimental model to examine the effect of tumor on depressive-like behavior. Female C57BL/6 mice were injected i.p. with syngeneic ID8 ovarian carcinoma. Experiment 1 measured sucrose intake before and after tumor incubation to assess the effect of tumor on anhedonic depressive-like behavior. Experiment 2 examined effects of tumor and social housing on anhedonia and a second depressive-like behavior, tail suspension test (TST) immobility. Systemic proinflammatory and antiinflammatory cytokines were measured following each experiment. Additional behaviors assessed the specificity of tumor's effect on depressive-like behavior. Tumor caused a reduction in sucrose intake relative to baseline and control levels (P<.05). Moreover, individually-housed tumor-bearing mice exhibited a lower sucrose preference than group-housed tumor-bearing or control mice in either housing condition (P<.05). Although tumor-bearing mice exhibited less locomotion than controls (P<.001), there was no significant effect of tumor on TST immobility. Tumor caused higher levels of systemic proinflammatory and antiinflammatory cytokines and smaller body weight (P<.05), but appetite and motor capacity were not significantly affected. Statistical mediation analysis showed that circulating interleukin-6 partially mediated the effect between tumor and home cage locomotion (P<.01) but not between tumor and sucrose intake. It is concluded that tumor elicits anhedonic depressive-like behavior in a murine model of ovarian cancer. This may have important implications for etiology of depression in the clinical cancer setting.

Copyright © 2010 Elsevier Inc. All rights reserved.

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Conflict of interest statement

Conflict of Interest Statement: All authors declare that there are no conflicts of interest.

Figures

Figure 1

Figure 1. Diagram for Experiments 1 and 2

Figure 2

Figure 2. Sucrose intake, food intake, and body weight between groups in Experiment 1

(A) To test for an effect of ovarian tumor on anhedonia, 1-hour sucrose intake was measured for control and tumor-bearing mice at baseline and 8-12 weeks post-injection. There was a significant interaction between tumor condition and time as tumor-bearing mice (diamond) (n = 29) consumed significantly less sucrose solution than control mice (triangle) (n = 18) at the end of the experiment, *P < .05. BW: body weight (B) To further examine the specificity of the effect of ovarian tumor on sucrose intake, 24-hour food intake and body weight were measured to test for an effect of ovarian tumor on appetite. Both experimental groups ate significantly less chow per body weight at the end of the experiment than at baseline (P < .001), but there was no significant difference (n.s.) between groups at the end of the experiment (P = .25 for interaction). (C) The interaction effect between time and tumor condition on body weight was significant as the increase in body weight over time was greater in control mice than in tumor-bearing mice, *P < .05.

Figure 3

Figure 3. Systemic proinflammatory and antiinflammatory cytokine levels in mice from Experiment 1

Tumor-bearing mice (n = 29) exhibited significantly higher levels of systemic IL-6, TNF-α, and IL-10 than control mice (n = 17) at 8-12 weeks post-injection, *P < .05, ***P < .001. Difference between groups was marginal for IL-4 (P = .09). §: Units are ng/mL. SQRT: square root transformed.

Figure 4

Figure 4. Sucrose preference and sucrose intake between groups in Experiment 2

(A) To control for any differences in thirst among animals, mice were exposed to sucrose solution only once at the end of tumor incubation to ensure measurement of both sucrose solution consumption and plain water consumption for determination of sucrose preference [Sucrose preference = (sucrose solution intake) / (sucrose solution intake + water intake)]. Individually-housed tumor-bearing mice (n = 10) exhibited a significantly lower sucrose preference in comparison to group-housed tumor-bearing mice (n = 8) and control mice that were individually-housed (n = 9) or group-housed (n = 10), *P < .05. (B) Tumor-bearing mice exhibited significantly less sucrose intake than control mice, *P < .05. (C) Individually-housed mice exhibited significantly less sucrose intake than group-housed mice, *P < .05.

Figure 5

Figure 5. TST immobility and locomotion between tumor-bearing mice and control mice in Experiment 2

(A) Tumor-bearing mice (n = 37) exhibited no significant difference (n.s.) from control mice (n = 36) in average immobile bout time (P = .73). (B) Tumor-bearing mice exhibited significantly less home cage locomotion than control mice, ***P < .001.

Figure 6

Figure 6. Systemic proinflammatory and antiinflammatory cytokine levels in mice from Experiment 2

Tumor-bearing mice in both housing conditions (n = 30) exhibited significantly higher levels of systemic IL-6, IL-17, and IL-10 than control mice in both housing conditions (n = 27) at 6-12 weeks post-injection, *P < .05, ***P < .001. §: Units are ng/mL. SQRT: square root transformed.

Figure 7

Figure 7. Cytokine mediation models

(A) Regression coefficients and significance values are noted for each path from tumor to cytokines and, after adjustment, from cytokines to locomotion in individually-housed mice from Experiments 1 and 2 (n = 82). Total effect of tumor and cytokines on locomotion is delineated by the c coefficient. Direct effect between tumor and locomotion, adjusting for cytokine mediators in model, is delineated by _c_′ coefficient. (B) Sucrose intake model (n = 66).

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