The selective neuropeptide Y Y5 agonist [cPP1–7,NPY19–23,Ala31,Aib32,Gln34]hPP differently modulates emotional processes and body weight in the rat

The neuropeptide Y (NPY) has been suggested to act as a major regulator of emotional processes and body weight. The full spectrum of biological effects of this peptide is mediated by at least four classes of receptors known as the Y1, Y2, Y4, and Y5 subtypes. However, the respective contribution of each of these receptor subtypes, especially the Y5 subtype, in emotional processes is still mostly unknown. In the present study, we investigated the effect of long term administration of a selective Y5 agonist [cPP1–7,NPY19–23,Ala31,Aib32,Gln34]hPP on emotional processes and body weight using two rat models of emotional dysfunctions, the corticosterone (CORT)-induced anxiety model as well as the olfactory bulbectomized (OBX) model of depression and anxiety in Wistar and Sprague-Dawley rats, respectively. The sub-chronic administration of the Y5 agonist reversed the high levels of locomotion, rearing and grooming in the open field test and the impaired social activity induced by OBX, while increased the percentage of entries and time in the open arm of the elevated plus maze in CORT-treated rats. Furthermore, this Y5 agonist increased body weight in both strains of control rats. These data further demonstrate that Y5 receptors are not only involved in the control of body weight but also mediate emotional processing under challenged conditions. Thus, the pharmacotherapeutic administration of a Y5 agonist could be considered as a potentially novel strategy to alleviate some forms of anxiety and depression in humans.