title: Social defeat stress induces hyperthermia through activation of thermoregulatory sympathetic premotor neurons in the medullary raphe region.
abstract: Psychological stress-induced hyperthermia is a fundamental autonomic response in mammals. However, the central circuitry underlying this stress response is poorly understood. Here, we sought to identify sympathetic premotor neurons that mediate a hyperthermic response to social defeat stress, a psychological stress model. Intruder rats that were defeated by a dominant resident conspecific exhibited a rapid increase in abdominal temperature by up to 2.0  °C. In these defeated rats, we found that expression of Fos, a marker of neuronal activation, was increased in the rostral medullary raphe region centered in the rostral raphe pallidus and adjacent raphe magnus nuclei. In this region, Fos expression was observed in a large population of neurons expressing vesicular glutamate transporter 3 (VGLUT3), which are known as sympathetic premotor neurons controlling non-shivering thermogenesis in brown adipose tissue (BAT) and thermoregulatory constriction of skin blood vessels, and also in a small population of tryptophan hydroxylase-positive serotonergic neurons. Intraperitoneal injection of diazepam, an anxiolytic agent, but not indomethacin, an antipyretic, significantly reduced both the stress-induced hyperthermia and Fos expression in these medullary raphe neuronal populations. Systemic blockade of β3 -adrenoreceptors, which are abundantly expressed in BAT, also attenuated the stress-induced hyperthermia. These results suggest that psychological stress signals activate VGLUT3-expressing medullary raphe sympathetic premotor neurons, which then drive hyperthermic effector responses including BAT thermogenesis through β(3) -adrenoreceptors.
authors: Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Battuvshin
authors: B
authors: Lkhagvasuren
authors: Yoshiko
authors: Y
authors: Nakamura
authors: Takakazu
authors: T
authors: Oka
authors: Nobuyuki
authors: N
authors: Sudo
authors: Kazuhiro
authors: K
authors: Nakamura
mesh_terms: D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004291:Dominance-Subordination; D007035:Hypothermia / Q000209:etiology*; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000473:pathology*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism
chemical_list: C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D058673:Adrenergic beta-3 Receptor Antagonists; D014151:Anti-Anxiety Agents; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D016761:Oncogene Proteins v-fos; D011412:Propanolamines; C482103:Slc17a8 protein, rat; D050496:Vesicular Glutamate Transport Proteins; D014365:Tryptophan Hydroxylase; D003975:Diazepam; D007213:Indomethacin