Obestatin induces depressive-like behavior in the forced swimming test in miceObestatin induces depressive-like behavior in the forced swimming test in miceObestatin

Obestatin is a preproghrelin gene-derived peptide isolated first from the rat stomach and identified as anorexigenic peptide ghrelin antagonist, reducing food intake and body weight gain. Since its discovery, multiple functions of this peptide have been revealed, including glucose metabolism, cardiac function, sleep, thirst, and neuronal survival among others. In the present study, we investigated the effect of the acute intracerebroventricular obestatin injection in the forced swimming test (FST), and on the Corticotropin-Releasing Hormone (CRH) and arginine vasopressin (AVP) gene expression in the amygdala and hypothalamus. Male, CFLP mice were used in the experiments and were treated with different doses of obestatin (0.5–1-1.5 μg/2 μl aCSF) and tested in the FST. Other groups of animals received pretreatment with the ghrelin receptor antagonist [D-Lys3]-growth hormone releasing peptide-6 ([D-Lys3] GHRP-6 or the CRH type 1 receptor antagonist antalarmin. According to our results, obestatin, in a dose of 1 µg increased the immobility time in the FST and decreased the swimming time indicating a depression-like behavior. Pretreatment with antalarmin or with the ghrelin receptor antagonist reversed the depression-like effects, by decreasing immobility time and increasing swimming time. Gene expression of Avp and Crh were upregulated after central obestatin administration in the amygdala. The presented results showing the depression-like behavior of obestatin, correlate with our previous studies indicating the anxiogenic-like effect of this peptide. The depressive-like effects might be mediated through multiple mechanisms, involving HPA axis activation, ghrelin signaling and AVP release, all of which merit further thorough investigations.