Neurokinin 3 receptor-expressing neurons in the median preoptic nucleus modulate heat-dissipation effectors in the female rat

KNDy neurons facilitate tail skin vasodilation and modulate the effects of estradiol on thermoregulation. We hypothesize that KNDy neurons influence cutaneous vasodilation via projections to neurons in the median preoptic nucleus (MnPO) that express the neurokinin 3 receptor (NK₃R). In support of this hypothesis, focal microinjections of senktide, an NK₃R agonist, into the MnPO lowers core temperature (T_CORE) in the female rat. To further study the role of MnPO NK₃R neurons in thermoregulation, these neurons were specifically ablated using a conjugate of a selective NK₃R agonist and saporin (NK₃-SAP). NK₃-SAP or blank-SAP (control) was injected into the MnPO/medial septum. Tail skin temperature (T_SKIN) and T_CORE were measured in ovariectomized rats exposed to 3 ambient temperatures (T_AMBIENT) before and after estradiol-17β (E₂) treatment. Before killing, we injected senktide (sc), monitored T_CORE for 70 minutes, and harvested brains for Fos immunohistochemistry. Ablation of MnPO NK₃R neurons lowered T_SKIN at neutral and subneutral T_AMBIENT regardless of E₂ treatment. However, ablation did not prevent the effects of E₂ on T_CORE and T_SKIN. In control rats, senktide injections induced hypothermia with numerous Fos-immunoreactive cells in the MnPO. In contrast, in NK₃-SAP rats, senktide did not alter T_CORE and minimal Fos-immunoreactive neurons were identified in the MnPO. These data show that NK₃R neurons in the MnPO are required for the hypothermic effects of senktide but not for the E₂ modulation of thermoregulation. The lower T_SKIN in NK₃-SAP-injected rats suggests that MnPO NK₃R neurons, like KNDy neurons, facilitate cutaneous vasodilation, an important heat-dissipation effector.