Neuromodulator hydrogen sulfide attenuates sickness behavior induced by lipopolysaccharide.

Sickness behavior reflects a state of altered physiology and central nervous system function that occurs during systemic infection or inflammation, serving as an adaptive response to illness. This study aims to elucidate the role of hydrogen sulfide (H 2 S) in regulating sickness behavior and neuroinflammatory responses in a rat model of systemic inflammation. Adult male Wistar rats were treated with lipopolysaccharide (LPS) to induce sickness behavior. Intracerebroventricular (i.c.v.) pretreatments included aminooxyacetic acid (AOAA), an inhibitor of H 2 S synthesis, and sodium sulfide (NaHS), an H 2 S donor. Behavioral assays were conducted, along with the assessment of astrocyte activation, as indicated by GFAP expression in the hypothalamus. Pretreatment with NaHS mitigated LPS-induced behavioral changes, including hypophagia, social and exploratory deficits, without affecting peripheral cytokine levels, indicating a central modulatory effect. AOAA, conversely, accentuated certain behavioral responses, suggesting a complex role of endogenous H 2 S in sickness behavior. These findings were reinforced by a lack of effect on plasma interleukin levels but significant reduction in GFAP expression. Our findings support the central role of H 2 S in modulating neuroinflammation and sickness behavior, highlighting the therapeutic potential of targeting H 2 S signaling in neuroinflammatory conditions. • Hydrogen sulfide eases behavioral impact of lipopolysaccharide in rats. • NaHS counters LPS-induced behavioral changes effectively in rodent models. • AOAA enhances LPS-induced hypophagia, pointing to complex H2S roles. • H2S demonstrates significant neuroprotective actions against LPS in CNS. • NaHS icv use shows no change in cytokine levels LPS-induced, indicating central action. [ABSTRACT FROM AUTHOR]