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Sickness behavior, characterized by on overall reduction in behavioral activity, is commonly observed after bacterial infection. Sickness behavior can also be induced by the peripheral administration of Gram-negative bacterial lipopolysaccharide (LPS) or interleukin-1beta (IL-1β), a pro-inflammatory cytokine released by LPS-activated macrophages. In addition to the microglia, the brain contains perivascular macrophages, which express the IL-1 type 1 receptor (IL-1R1). In the present study, we assessed the role of brain perivascular macrophages in mediating IL-1β-induced sickness behavior in rats. To do so, we used intracerebroventricular (icv) administration of an IL-1β-saporin conjugate, known to eliminate IL-R1-expressing brain cells, prior to systemic or central IL-1β injection. Icv IL-1β-saporin administration resulted in a reduction in brain perivascular macrophages, without altering subsequent icv or ip IL-1β-induced reductions in food intake, locomotor activity, and social interactions. In conclusion, the present work shows that icv IL-1β-saporin administration is an efficient way to target brain perivascular macrophages, and to determine whether these cells are involved in IL-1β-induced sickness behavior.

Brain Perivascular Macrophages Do Not Mediate Interleukin-1-Induced Sickness Behavior in Rats