BACKGROUND: Numerous physiological properties have been documented in the literature pertaining to spexin, such as its role in appetite regulation. Therefore, the present research aimed to assess the impacts of centrally administering spexin and its interaction with opioid and melanocortin receptors on feeding behavior in neonatal broiler chicks. In experiment 1, the chickens were administered intracerebroventricular (ICV) injection of saline and spexin at varying doses of 5, 7.5 and 10 nmol. During the experiment 2, the broilers were subjected to an ICV injection containing saline, β-FNA (µ-opioid receptor antagonist, 5 µg), spexin (10 nmol), and a mixture of β-FNA plus spexin. Experiments 3 to 6 bore resemblance to experiment 2, with the exception that NTI (δ-opioid receptor antagonist, 5 µg), nor-BNI (κ-opioid receptor antagonist, 5 µg), SHU9119 (MC3/MC4 receptor antagonist, 0.5 nmol) and MCL0020 (MC4 receptor antagonist, 0.5 nmol) were administered instead of β-FNA. Then, the birds were promptly placed back into their individual cages and cumulative food intake was assessed at intervals of 30, 60, and 120 min postinjection. RESULTS: Spexin demonstrated a significant and dose-dependent decrease in food intake when compared to the control group (P <
0.05). Co-injection of β-FNA + spexin diminished spexin-induced hypophagia (P <
0.05) whereas concurrent administration of NTI and nor-BNI with spexin led to an amplification of the decrease in food consumption induced by spexin (P <
0.05). Additionally, anorexigenic impact of spexin was reversed by combined injection of SHU9119 and MCL0020 with spexin (P <
0.05). CONCLUSION: These observations suggest that both opioid and melanocortin receptors play crucial role in spexin-induced hypophagia.