Imidazoline 1 receptors mediate the hyperthermia induced by preoptic agmatine application in male rats

Previous studies have confirmed that microinjection of agmatine into the preoptic area (POA) induces hyperthermia in male rats, yet its receptor mechanism is known little. In the present study, using agonists and antagonists for imidazoline receptors (IRs) and α2-adrenoceptors (α2-ARs), to which agmatine binds with high affinity, we explored the roles of IRs and α2-ARs in hyperthermia induced by intra-POA agmatine in male rats. We found that intra-POA administration of the I1R agonist moxonidine elevated the core temperature and physical activity in conscious rats, enhanced brown adipose tissue (BAT) thermogenesis and shivering in anesthetized rats, and depressed the warm-sensitive neurons (WSNs) in POA slices in vitro, which aligned with previously demonstrated agmatine effects. Meanwhile, the selective I1R antagonist AGN192403 attenuated these effects. Moreover, fluorescence immunohistochemical analysis of Nischarin (a natural functional I1R) indicated that I1Rs were distributed in the POA. However, neither agonists nor antagonists for I2R or α2-ARs mimicked or attenuated the effects of intra-POA agmatine. In conclusion, we demonstrated that it is I1R rather than I2R or α2-ARs that mediates intra-POA agmatine-induced hyperthermia by elevating physical activity, BAT thermogenesis and shivering, likely through depression of POA WSNs. These results indicate an important role of the preoptic agmatine–I1R system in the thermoregulation.