Rathner JA, Madden CJ, Morrison SF. Central pathway for spontaneous and prostaglandin E2-evoked cutaneous vasoconstriction. Am J Physiol Regul Integr Comp Physiol 295: R343-R354, 2008. First published May 7, 2008 doi:10.1152/ajpregu.00115.2008.-A reduction of heat loss to the environment through increased cutaneous vasoconstrictor (CVC) sympathetic outflow contributes to elevated body temperature during fever. We determined the role of neurons in the dorsomedial hypothalamus (DMH) in increases in CVC sympathetic tone evoked by PGE2 into the preoptic area (POA) in chloralose/urethane-anesthetized rats. The frequency of axonal action potentials of CVC sympathetic ganglion cells recorded from the surface of the tail artery was increased by 1.8 Hz following nanoinjections of bicuculline (50 pmol) into the DMH. PGE2 nanoinjection into the POA elicited a similar excitation of tail CVC neurons (ϩ2.1 Hz). Subsequent to PGE2 into the POA, muscimol (400 pmol/side) into the DMH did not alter the activity of tail CVC neurons. Inhibition of neurons in the rostral raphé pallidus (rRPa) eliminated the spontaneous discharge of tail CVC neurons but only reduced the PGE2-evoked activity. Residual activity was abolished by subsequent muscimol into the rostral ventrolateral medulla. Transections through the neuraxis caudal to the POA increased the activity of tail CVC neurons, which were sustained through transections caudal to DMH. We conclude that while activation of neurons in the DMH is sufficient to activate tail CVC neurons, it is not necessary for their PGE2-evoked activity. These results support a CVC component of increased core temperature elicited by PGE2 in POA that arises from relief of a tonic inhibition from neurons in POA of CVC sympathetic premotor neurons in rRPa and is dependent on the excitation of CVC premotor neurons from a site caudal to DMH. rostral raphé pallidus; thermoregulation; fever; dorsomedial hypothalamus; preoptic hypothalamus IN BOTH HUMANS (19,20,43) and rats (53) cutaneous vasoconstrictor (CVC) tone regulates heat loss to the environment and contributes importantly to the maintenance of normal body temperature and to the development of fever. The essential role for the generation of PGE 2 in the preoptic area (POA) in the production of fever has led to the use of nanoinjections of PGE 2 into the POA to understand the neural pathways controlling thermoregulatory effectors during the febrile response. Similarly, observations of thermal effector responses elicited by changes in skin (T SK ) or core temperature (T C ) have provided important information on the central neural networks responsible for body temperature homeostasis. Such studies have been pursued most extensively with regard to the sympathetic neural regulation of non-shivering thermogenesis in rodent brown adipose tissue (BAT), a highly metabolic tissue in which heat production contributes significantly to the defense of body temperature in cold environments and to the elevation of body temperature during the febrile response. The neur...