Aim of investigation. The proinflammatory cytokine interleukin-1b (IL-1b) influence neuroendocrine activity, promote central neurotransmitter alterations and induce a constellation of symptoms collectively referred as sickness behaviors. This cytokine may also elicit anxiety and anhedonia and have been associated with psychological disturbances in humans. The melanocortin neuropeptides, such as alpha melanocyte-stimulating hormone (a-MSH), antagonize many actions of IL-1, including fever, anorexia and HPA axis activation. However, it is unknown if melanocortins modulate anxiety induced by IL-1b. The objective of the present study was to establish the effect of melanocortins on IL-1b-induced anxiety like behavior and the specific melanocortin receptors involved.
Methods. The present study evaluated the effects of Intracerebroventricular (i.c.v.) administration of IL-1b (30 ngl) and melanocortins receptors agonists (a-MSH 0,2 mg and g-MSH 2 mg) and MC4-R antagonist HS014 ( ), on elevated plus-maze test.
Results. Injection of IL-1b induced an axiogenic-like response, as indicated by reduced open arms entries and time spent on the open arms.
The administration of a-MSH reversed IL-1b-induced anxiety. Coadministration of the MC4-R antagonist HS014 inhibited the effect of a-MSH. The treatment with g-MSH, a selective agonist of MC3-R, did not affect the anxiety response to IL-1b.
Conclusion. These data suggest that melanocortins, through central MC4-R can modulate the anxiety like behavior induced by IL-1b.
