Anxiety-like behavior induced by IL-1 beta is modulated by alpha- MSH through central melanocortin-4 receptor

CRAGNOLINI, ANDREA BEATRIZ; SCHIÖTH, HELGI BIRGIR; SCIMONELLI, TERESA NIEVES

Venecia, Italia

Congreso; International Congress of Neuroimmunology; 2004

The proinflammatory cytokine interleukin-1 beta (IL-1 beta) influences neuroendocrine activity and promotes central effects such as anxiety and anhedonia. The melanocortin neuropeptides, like alpha melanocyte stimulating hormone (alpha-MSH), antagonize many actions of IL-1, including fever, anorexia and HPA axis activation through specific melanocortin receptors in central nervous system. However, it is unknown if melanocortins can modulate IL-1beta-induced anxiety. The objective of the present study was to establish the effect of MSH peptides on IL-1 beta-induced anxiety-like behavior and the type of melanocortin receptors involved. The present study evaluated the effects of intracerebroventricular (i.c.v.) administration of IL-1 beta (30 ng) and melanocortin receptor agonists: alpha-MSH, an MC3/MC4-R agonist (0,2 ug) and gamma-MSH an MC3-R agonist (2 ug) or HS014, an MC4-R antagonist(2 ug), on elevated plus-maze test. Injection of IL-1 beta induced an axiogenic-like response, as indicated by reduced open arms entries and time spent on open arms. The administration of alpha-MSH reversed IL-1 beta-induced anxiety. Coadministration of HS014 inhibited the effect of alpha-MSH. The associated treatment with gamma-MSH did not affect the anxiety response to IL-1beta. These data suggest that melanocortins, through central MC4-R can modulate the anxiety-like behavior induced by IL-1 beta.