The anorexigenic effect of cholecystokinin octapeptide in a goldfish model is mediated by the vagal afferent and subsequently through the melanocortin- and corticotropin-releasing hormone-signaling pathways

We have been extensively investigating the mechanisms by which neuropeptides regulate feeding behavior by using a goldfish (Carassius auratus) model. In this species, the anorexigenic action of melanocortin peptide is centrally mediated via the corticotropin-releasing hormone (CRH)/CRH receptor neuronal system, whereas sulfated cholecystokinin octapeptide (CCK-8s) is involved in the appetite regulation as a peripheral anorexigenic factor. The aim of the present study was to identify the mechanism of the anorexigenic effect of peripherally injected CCK-8s, which has not yet been identified in goldfish. Co-administration of capsaicin, a neurotoxin that destroys primary sensory afferents, at 100 nmol/g BW, blocked the anorexigenic action of intraperitoneally injected CCK-8s (100 pmol/g BW), whereas the anorexigenic action of intracerebroventricularly injected CCK-8s (5 pmol/g BW) was not blocked by co-administration of capsaicin. Pre-treatment with a specific CRH receptor antagonist, α-helical CRH(9–41), attenuated the anorexigenic action of CCK-8s. The expression level of CRH mRNA in the diencephalic tissue of the CCK-8s-injected group was not changed, but the level of proopiomelanocortin mRNA was significantly increased at 1 h after treatment. Therefore, we have identified for the first time that the reduction of appetite induced by peripherally injected CCK-8s in goldfish appears to be mediated by the vagal afferent and subsequently through the melanocortin- and corticotropin-releasing hormone-signaling pathways.

Research highlights▶ IP injection of CCK-8s induces anorexigenic action in goldfish. ▶ CCK-8s-induced anorexigenic action is blocked by treatments with capsaicin or the CRH receptor antagonist. ▶ POMC mRNA level in the diencephalon is increased after treatment with CCK-8s. ▶ Anorexigenic action of CCK-8s is mediated by the vagal afferent and subsequently through the melanocortin- and CRH-signaling pathways.