Anxiety-like behavior induced by IL-1β is modulated by α-MSH through central melanocortin-4 receptors

The proinflammatory cytokine interleukin-1β (IL-1β) influences neuroendocrine activity and produces other effects, including fever and behavioral changes such as anxiety. The melanocortin neuropeptides, such as alpha-melanocyte-stimulating hormone (α-MSH), antagonize many actions of IL-1, including fever, anorexia and hypothalamic-pituitary-adrenal (HPA) axis activation through specific melanocortin receptors (MC-R) in the central nervous system. The objective of the present study was to establish the effect of MSH peptides on IL-1β-induced anxiety-like behavior and the melanocortin receptors involved. We evaluated the effects of intracerebroventricular (i.c.v.) administration of IL-1β (30 ng) and melanocortin receptor agonists: α-MSH, an MC3/MC4-R agonist (0.2 μg) or γ-MSH, an MC3-R agonist (2 μg) or HS014, an MC4-R antagonist (2 μg), on an elevated plus-maze (EPM) test. Injection of IL-1β induced an anxiogenic-like response, as indicated by reduced open arms entries and time spent on open arms. The administration of α-MSH reversed IL-1β-induced anxiety with co-administration of HS014 inhibiting the effect of α-MSH. However, the associated treatment with γ-MSH did not affect the anxiety response to IL-1β. These data suggest that α-MSH, through central MC4-R can modulate the anxiety-like behavior induced by IL-1β.