Repeated exposure of male mice to low doses of lipopolysaccharide: Dose and time dependent development of behavioral sensitization and tolerance in an automated light–dark anxiety test

Banasikowski, Tomek J; Cloutier, Caylen J.; Ossenkopp, Klaus‐Peter; Kavaliers, Martin

doi:10.1016/j.bbr.2015.03.004

Cited by 20 publications

(14 citation statements)

References 65 publications

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“…This treatment did not significantly affect alcohol intake, although there was a trend of an increase during DID10 in the group of mice which had received LPS before the DID procedure and also between the DID cycles. Comparison of water consumption and body weights after repeated LPS injections suggests formation of some tolerance to the sickness reaction, which is consistent with previous reports (Banasikowski, Cloutier, Ossenkopp, & Kavaliers, 2015;Engeland, Nielsen, Kavaliers, & Ossenkopp, 2001). Thus, it is possible that higher repeated LPS doses might have produced clearer effects on alcohol intake, but this remains to be studied.…”

Section: Discussionsupporting

confidence: 92%

Alcohol intake in two different mouse drinking models after recovery from the lipopolysaccharide-induced sickness reaction

Lainiola

Lindén

2017

Alcohol

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Neuroinflammation may play an important role in the development of alcohol addiction. Recent preclinical reports suggest that enhanced innate immune system signaling increases consumption of alcohol. Our aim was to study whether consequences of lipopolysaccharide (LPS)-induced sickness reaction increase long-term alcohol intake. Adult male C57BL/6J mice, housed in individually ventilated cages, were injected with LPS intraperitoneally (i.p.) and allowed to recover from an acute sickness reaction for 1 week before analysis of their alcohol intake in two different drinking models. Effects of LPS challenge were tested in a continuous two-bottle free choice test with increasing concentrations of alcohol and in a drinking in the dark (DID) binge model. In addition, the effect of repeatedly administered LPS during abstinence periods between binge drinking was analyzed in the DID model. In addition, the DID model was used to study the effects of the microglia inhibitor minocycline (50 mg/kg/day, 4 days) and purinergic P2X7 receptor antagonist Brilliant Blue G (75 mg/kg/day, 7 days) on alcohol intake. In contrast to previous findings, pretreatment with a 1-mg/kg dose of LPS did not significantly increase ethanol consumption in the continuous two-bottle choice test. As a novel finding, we report that increasing the LPS dose to 1.5 mg/kg reduced consumption of 18 and 21% (v/v) ethanol. In the DID model, pretreatment with LPS (0.2-1.5 mg/kg) did not significantly alter 15% or 20% ethanol consumption. Neither did repeated LPS injections affect binge alcohol drinking. Minocycline reduced alcohol, but also water, intake regardless of LPS pretreatment. No data on effects of P2X7 antagonists on alcohol consumption have been previously published; therefore, we report here that subchronic Brilliant Blue G had no effect on alcohol intake in the DID model. As a conclusion, further studies are needed to validate this LPS model of the interaction between immune system activation and alcohol consumption.

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Section: Discussionsupporting

confidence: 92%

Alcohol intake in two different mouse drinking models after recovery from the lipopolysaccharide-induced sickness reaction

Lainiola

Lindén

2017

Alcohol

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“…The next experiments administered lipopolysaccharide (LPS) to the treatment groups to evaluate the response to an immune challenge. LPS is a bacterial endotoxin derived from the cell wall of Gram negative bacteria and is commonly used as an immune stimulus with welldocumented physiologic and behavioral responses characterized as "sickness behavior" (Banasikowski et al, 2015). Primed microglia with a reactive phenotype have an exacerbated response to a single LPS in-jection, resulting in larger increases in central and peripheral inflammatory markers (e.g.…”

Section: Discussionmentioning

confidence: 99%

Mammary tumor and mastectomy synergistically promote neuroinflammation in a breast cancer survivor model

et al. 2019

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Understanding why breast cancer survivors are at an increased risk for cognitive and affective disorders is essential for developing targeted treatment plans and improving quality of life. Microglia priming results in chronic neuroinflammation and can contribute to neuronal degeneration and dysfunction, thereby offering a potential mechanism for altered brain function that persists after tumor removal. This study examined whether mammary tumors alter microglia and augment the inflammatory profile and behavior of mice. To test this, non-metastatic mammary tumor cells (67NR) were injected orthotopically into the mammary glands of BALB/c mice, allowed to grow for 16 days, and then the tumors were removed via mastectomy. Following a 14day surgical recovery, the mice were challenged with lipopolysaccharide (LPS), and then central and peripheral inflammation, anxiety, and depressive-like behavior were evaluated. Here we show that major central and peripheral inflammatory markers were not altered by tumor growth nor mastectomy surgery alone. However, hippocampal mRNA expression of major proinflammatory cytokines IL-1β and TNFα was increased in tumor removal animals, persisting past surgical recovery. Nonetheless, the immune and behavioral responses following LPS administration were comparable among groups. In sum, these data demonstrate that the combination of tumor and mastectomy promotes neuroinflammation; however, immune challenge did not elucidate this inflammation as maladaptive for the host.

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“…My results indicate that guppy response to the visual cues increased as these cues were repeated through time; this pattern might be considered indicative of the fish becoming sensitized to the cues. “Behavioral sensitization” refers to increased responsiveness following arousal by rewarding or punishing experiences, with responsiveness increasing through repeated exposure, and is common to animals across taxa (e.g., honeybees, Apis mellifera , see Mallon et al 2003 ; mice, Mus musculus , see Banasikowski et al 2015 ; and humans, Homo sapiens , see Strakowski et al 1996 ). However, I consider this explanation of the results unlikely: if sensitization were driving the results, given the number of times the visual cues were repeated after the disturbance, I would have expected the response to the visual cues to exceed the levels attained in the early stages of the trials.…”

Section: Discussionmentioning

confidence: 99%

Keeping eyes peeled: guppies exposed to chemical alarm cue are more responsive to ambiguous visual cues

Stephenson

2016

Behav Ecol Sociobiol

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Information received from the visual and chemical senses is qualitatively different. For prey species in aquatic environments, visual cues are spatially and temporally reliable but risky as the prey and predator must often be in close proximity. Chemical cues, by contrast, can be distorted by currents or linger and thus provide less reliable spatial and temporal information, but can be detected from a safe distance. Chemical cues are therefore often the first detected and may provide a context in which prey respond to subsequent ambiguous cues (“context hypothesis”). Depending on this context, early chemical cues may also alert prey to attend to imminent cues in other sensory modalities (“alerting hypothesis”). In the context of predation risk, for example, it is intuitive that individuals become more responsive to subsequent ambiguous cues across sensory modalities. Consistent with the context hypothesis, guppies, Poecilia reticulata, exposed to conspecific alarm cue reduced activity, a classic fright response among fish, in response to a water disturbance more than those exposed to cues of unharmed conspecifics or a water control. Despite this reduction in activity, guppies exposed to alarm cue were more attentive to visual cues than those exposed to the other chemical cues, as predicted by the alerting hypothesis. These responses contrasted with those of guppies exposed to chemical cues of undisturbed, unharmed conspecifics, which were relatively unaffected by the disturbance. This is the first study indicating that unambiguous cues detected by one sensory modality affect animal responses to subsequent ambiguous multimodal cues.Significance statementIn moving water, chemical cues can be detected over longer distances than visual cues; they may therefore be detected first and alert animals to imminent visual cues. This effect is likely to be particularly important if these chemical cues are indicative of predation. I investigated how different chemical cues affect (1) guppy response to an ambiguous water disturbance and (2) their responsiveness to subsequent ambiguous visual cues. Guppies based their responses to ambiguous cues on the context implied by chemical cues: those exposed to chemical cues indicative of predation reduced activity, a classic fright response, but increased responsiveness to visual cues, relative to those exposed to control chemical cues. This is the first study to show that unambiguous cues detected by one sense affect animal responses to ambiguous cues detected by other senses.Electronic supplementary materialThe online version of this article (doi:10.1007/s00265-016-2076-4) contains supplementary material, which is available to authorized users.

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Repeated exposure of male mice to low doses of lipopolysaccharide: Dose and time dependent development of behavioral sensitization and tolerance in an automated light–dark anxiety test

Cited by 20 publications

References 65 publications

Alcohol intake in two different mouse drinking models after recovery from the lipopolysaccharide-induced sickness reaction

Alcohol intake in two different mouse drinking models after recovery from the lipopolysaccharide-induced sickness reaction

Mammary tumor and mastectomy synergistically promote neuroinflammation in a breast cancer survivor model

Keeping eyes peeled: guppies exposed to chemical alarm cue are more responsive to ambiguous visual cues

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