Anxiety-like behavior induced by IL-1beta is modulated by alpha-MSH through central melanocortin-4 receptors.
The proinflammatory cytokine interleukin-1beta (IL-1beta) influences neuroendocrine activity and produces other effects, including fever and behavioral changes such as anxiety. The melanocortin neuropeptides, such as alpha-melanocyte-stimulating hormone (alpha-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-1beta-induced anxiety-like behavior and the melanocortin receptors involved. We evaluated the effects of intracerebroventricular (i.c.v.) administration of IL-1beta (30 ng) and melanocortin receptor agonists: alpha-MSH, an MC3/MC4-R agonist (0.2 microg) or gamma-MSH, an MC3-R agonist (2 microg) or HS014, an MC4-R antagonist (2 microg), on an elevated plus-maze (EPM) test. Injection of IL-1beta induced an anxiogenic-like response, as indicated by reduced open arms entries and time spent on open arms. The administration of alpha-MSH reversed IL-1beta-induced anxiety with co-administration of HS014 inhibiting the effect of alpha-MSH. However, the associated treatment with gamma-MSH did not affect the anxiety response to IL-1beta. These data suggest that alpha-MSH, through central MC4-R can modulate the anxiety-like behavior induced by IL-1beta.
Cragnolini
Andrea Beatríz
AB
Departamento Farmacología, Facultad de Ciencias Químicas, Haya de la Torre y Medina Allende, Ciudad Universitaria, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina.
Schiöth
Helgi Birgir
HB
Scimonelli
Teresa Nieves
TN
D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal; D002490:Central Nervous System; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D018782:Maze Learning; D009479:Neuropeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism*; D019825:gamma-MSH / Q000378:metabolism
D007375:Interleukin-1; D009479:Neuropeptides; D010455:Peptides; D044105:Receptor, Melanocortin, Type 4; D019825:gamma-MSH; D000521:alpha-MSH