AGH, A NOVEL HEMOGLOBIN-DERIVED PEPTIDE, TARGETS SEROTONERGIC RECEPTORS TO INDUCE ANTINOCICEPTION IN MICE, WITHOUT INDUCING ANXIETY-DEPRESSIVE-LIKE BEHAVIOR

AGH (AGHLDDLPGALSAL), a novel bioactive peptide derived from the alpha-chain of hemoglobin, induces peripheral antinociceptive effect in rats. In the present study the systemic antinociceptive profileof AGH was examined in mice evaluated by the hot plate test or in submitted to the CFA-induced mechanical hyperalgesia and evaluated by electronic von Frey. The mechanisms involved on AGH-induced antinociception as well as anxiety-depressive-like behaviorwere also evaluated. Intraperitoneal administration of AGH (25 mg/ Kg) reversed CFA-induced non-opioid mechanical allodynia at the 3rd and 6th h after its injection. On the other hand, an opioid-mediated antinociception was observed when mice were evaluated at the hot plate test. Intraperitoneal pretreatment with methysergide (5-HT serotonergic receptor antagonist) attenuated antinociceptive effect induced byAGH on CFA-induced hyperalgesia. However, yohimbine (α2-adrenergic receptor antagonist) did not affect antinociception. To investigate whether AGH could induce changes in spontaneous motor activity or anxiety-depressive-like behavior, mice were evaluated by the open field test, tail suspension test and forced swimming test, respectively. No behavioral changes were observed for AGH-treated mice. These results demonstrate that AGH induces systemic antinociception, by targeting serotonergic receptors and without inducing behavioral changes in mice