Effects of interleukin-1 and endotoxin in the forced swim and tail suspension tests in mice

Abstract

Male CD-1 mice were administered interleukin-1β (IL-lβ) and bacterial endotoxin (lipopolysaccharide, LPS) and subsequently tested in the tail suspension test (TST), the Porsolt forced swim test (FST), and in the open field. IL-1β (100, 300 and 1000 ng/mouse) injected intraperitoneally (i.p.) 90 min before the test induced a dose-dependent increase in the time spent immobile in the TST and the time spent floating in the FST. These responses were statistically significant only at the higher doses of IL-1β (300 and 1000 ng). Nevertheless, all three doses of IL-1β significantly decreased line crossings and rears in the open field and depressed food intake and body weight. Very similar effects were induced by LPS. Doses of 1 and 5 μg i.p. increased immobility time in the TST and floating time in the FST, but the same doses strongly depressed locomotor activity and body weight.These results indicate that both IL-1β and LPS can induce depression-like effects in the TST and the FST. However, the doses necessary to induce these changes reduced feeding and activity in an open field, so that the effects observed in the FST and TST could be attributed to a general reduction in locomotor activity. Thus the results obtained in these two animal tests commonly used to test antidepressant properties do not provide strong support for an IL-1 hypothesis of depression.

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

“…37,46 Changes in open-field behavior have also been documented in animals administered cytokines in isolation, including TNFalpha and IL-1 and in animals with relevant cytokine genes deleted or overexpressed. 23,[39][40][41][42][47][48][49] Taken together with our results, these findings support the notion that cytokines released during immune activa- were measured over 5 min in ADX WT or TNF-R1-KO mice (n = 5-10 animals per group). Data were analyzed by a twoway ANOVA, and group differences were assessed using the Student-Newman-Keuls post hoc test of significance.…”

“…57,58 In addition, as noted above, TNFalpha effects may be mediated by induction of downstream cytokines such as IL-1, which has been shown to have a behavioral profile similar to TNFalpha in open-field testing. [40][41][42] Finally, consideration should be given to the possibility that reduced host responses to viral infection in TNF-R1-KO mice may be responsible (in relatively non-specific fashion) for the reversal of anxiety-like behaviors in glucocorticoid-deficient, MCMV-infected animals. As mentioned previously, TNF-R1-KO mice have been shown to exhibit reduced host responses.…”

“…Indeed, as noted above, IL-1 has been shown to reduce locomotor activity both alone and in combination with IL-6. [40][41][42]60 Given the critical role played by glucocorticoids in regulating immune responses (especially restraining inflammatory responses), patient populations with altered glucocorticoid signaling as result of reduced hormone or reduced glucocorticoid receptor expression/function, including post-traumatic stress disorder (PTSD) and major depression, may be especially vulnerable to the pathological/behavioral consequences of prolonged exposure to elevated circulating levels of proinflammatory cytokines. Indeed, both of these disorders have been found to be associated with an exaggerated inflammatory responses including increases in plasma concentrations of TNF-alpha and IL-6, and both are associated with increased symptoms of anxiety and alterations in locomotor activity, including psychomotor slowing and fatigue.…”

“…32,33 Moreover, open-field behavior has been shown to be altered in cytokine-treated and infected animals as well as animals with autoimmune disease. 21,28,[34][35][36][37][38][39][40][41][42] In addition, since TNF-alpha has been demonstrated to mediate MCMV-induced consequences on survival, we examined the possibility that TNF-alpha might also contribute to behavioral alterations in MCMV-infected animals. To abrogate TNF-alpha activity, TNF-alpha receptor 1 (TNFRp55) knockout (TNF-R1-KO) mice were employed.…”

Acute stress-induced changes in hormone and lipid levels in mouse plasma

“…Recently, stress-induced changes in liver lipid metabolism have been hypothesised to occur in rats (Gao et al 2013). For example, rats exhibited lower HDL-C and higher LDL-C levels than normal rats in an open-field test that was conducted to induce acute stress (Dunn and Swiergiel 2005). Based on the hormonal changes in plasma (Figure 3), we suggest that acute stress enhanced the release of CORT and insulin, and attenuated the release of T 3 and T 4 .…”