Effects of Phoenixin-14 on anxiolytic-like behavior in mice

Phoenixin is an amidated neuropeptide, which is widely distributed in brain and periphery regions and is known for its key role in reproduction. Phoenixin-14 (PNX-14), one of the endogenous active isoforms, was reported to regulate pituitary gonadotrophin secretion by increasing the expression of the GnRH receptor mRNA. Studies showed that GnRH could regulate brain responses to anxiety. However, the role of PNX-14 in anxiety was largely unclear. Here, we investigated that the effects of PNX-14 in anxiety-related behavior in adult mice via the open field and elevated plus maze. PNX-14 was administered intracerebroventricularly (i.c.v.) in different doses (5, 10, 25 and 50 nmol), and dose-dependently induced anxiolytic effects. Then this anxiolytic action was presented after PNX-14 injected into the anterior hypothalamic area (AHA), while PNX-14 infused into the amygdala did not exert anxiolytic effects. GnRH receptor antagonist (Cetrorelix) could significantly antagonize the anxiolytic effects of PNX-14, while Atosiban, a competitive vasopressin/oxytocin receptor antagonist could not. Moreover, PNX-14 could significantly lower the core temperature and Cetrorelix could block this effect of PNX-14. Additionally, the AHA infusion of PNX-14 (5 nmol) increased the expression level of the GnRH mRNA in the hypothalamus and plasma concentrations of GnRH. Similarly, i.c.v. injection of PNX-20 also reduced the core temperature and exerted anxiolytic effects. Taken together, centrally injected PNX-14 generates anxiolytic effects in mice, via the activation of the AHA GnRH system.