Dehydroepiandrosterone-sulfate did not mitigate sickness behavior in mice.
In response to lipopolysaccharide (LPS), macrophages secrete cytokines that transmit a message to the brain and induce sickness behavior. Because dehydroepiandrosterone (DHEA) and its sulfated ester (DHEA-S) reportedly improve mental health and modulate cytokine production, we hypothesized that DHEA-S administration would inhibit LPS-induced sickness behavior. Mice were provided drinking water with 0% or 0.01% DHEA-S for 2 weeks and then injected intraperitoneally with saline or LPS (1 microg). Sickness behavior was quantified using a social investigation paradigm, and DHEA-S in plasma and brain was determined at the study's end. DHEA-S did not affect water intake, food intake, or body weight during the 2-week period. As anticipated, LPS depressed social behavior. The maximum depression was observed 2 h postinjection, after which social investigation steadily increased until returning to baseline level at 8 h. DHEA-S did not mitigate the effects of LPS on social behavior even though DHEA-S in plasma and brain was increased 150- and 6-fold, respectively, in mice given DHEA-S. In a separate study, mice were given DHEA-S for 3 months and then challenged with LPS. Consistent with the first study, LPS reduced social behavior irrespective of DHEA-S treatment. However, 3 months administration of DHEA-S reduced the depression from baseline after injection of saline or LPS. DHEA-S in plasma and brain for mice given DHEA-S for 3 months was similar to that observed after 2 weeks. Collectively, these results suggest that DHEA-S has neuromodulatory effects but is ineffective at ameliorating LPS-induced sickness behavior.
Division of Nutritional Sciences, Department of Animal Sciences, University of Illinois, 1207 West Gregory Drive, Urbana, IL 61801, USA.
Jing
J
Chen
Rodney W
RW
Johnson
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism / Q000627:therapeutic use*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000523:psychology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012919:Social Behavior; D051197:Toll-Like Receptor 4
D016207:Cytokines; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D019314:Dehydroepiandrosterone Sulfate