Central effect of vasotocin 4 receptor (VT4R/V1aR) antagonists on the stress response and food intake in chicks given neuropeptide Y (NPY)

Abstract

Previous studies identified SR-49059 as a most effective antagonist of the avian vasotocin 4 receptor (VT4R) compared to other candidate blockers including the Manning compound using in silico 3 dimensional (3D) modeling/docking analysis of the chicken VT4R and an in vitro anterior pituitary cell culture study. The present experiments were designed to validate whether SR-49059 and the Manning compound would likewise be effective in vivo in blocking the VT4R when applied intracerebroventricularly (ICV) to chicks. Two treatments were tested, a stressor (immobilization) and administration of neuropeptide Y (NPY), a potent orexigenic compound. In the first experiment, birds were given the Manning compound, SR-49059 or physiological saline ICV followed by immobilization stress. Blood samples were taken and corticosterone (CORT) was determined by radioimmunoassay. It was hypothesized that both antagonists would reduce the stress response. A second experiment examined the role of the VT4R in food intake regulation. The Manning compound, SR-49059 or physiological saline was administered prior to NPY and food intake was monitored for 1h. It was hypothesized that each of the two antagonists coupled with NPY would augment food intake above the intake resulting from saline plus NPY administration. Related to the second experiment was a third that examined the difference between the effect of central administration of NPY versus SR-49059 in releasing CORT. Results of the first study showed that the Manning compound or SR-49059 prior to stress decreased CORT levels compared to controls while the second experiment showed that SR-49059 or the Manning compound plus NPY, enhanced food intake above that of the experimental group given saline and NPY. The last study showed that NPY increased plasma CORT above birds given SR-49059 centrally or saline administered controls. Taken together, results suggest that the avian VT4R is involved in the central neuroendocrine stress response as well as functions in appetite regulation by mediating an anorexigenic effect similar to what has been reported in mammals for the V1aR. In conclusion, similar to the past in silico and in vitro tests, the current in vivo experiments showed SR-49059 to be a most efficacious avian vasotocin receptor antagonist. Therefore based upon results of functional tests utilizing a highly specific mammalian antagonist, SR-49059, to the mammalian V1aR that likewise was most effective in blocking the avian VT4R and past reported high sequence homology between the mammalian V1aR and the VT4R, it is recommended that the chicken VT4R be renamed the avian V1aR to facilitate better communication among scientists involved in comparative studies.

Arginine vasopressin: Direct and indirect action on metabolism

“…Similar results were obtained from the studies of avian AVT V1a receptor, which is highly homologous to mammalian AVP V1a receptor, and is associated with the regulation of food intake in chickens by modulating neurons that synthesize and release anorexigenic neuropeptides [ 68 , 69 ].…”

Distribution and variation of neuropeptide Y in the brain of native Thai chicken

“…26,27 NPY in the ROT has been suggested to be involved with vasotocin (VT) in controlling feeding response in birds. 49,50 However, our results showed that the nucleus that responded to food restriction is the PVN. Therefore, future research is required to confirm whether NPY in the area around the ROT contributes with VT in regulation of food intake in birds.…”

Female reproductive state is associated with changes in distinct arginine vasotocin cell types in the preoptic area of Astatotilapia burtoni

“…In goldfish, intracerebroventricular injections of AVT have an anorexigenic effect, with fish decreasing their cumulative food intake in a dose‐dependent response (Araishi, Watanabe, Yamazaki, Nakamachi, & Matsuda, 2019). Similarly, central mesotocin administration in chicks, but not peripheral administration, inhibits feeding behaviors (Masunari, Cline, Khan, & Tachibana, 2016), and AVT modulates NPY‐induced food intake (Kuenzel, Hancock, Nagarajan, Aman, & Kang, 2016). Perhaps this population of avt cells in A .…”