Raphe pallidus neurons mediate prostaglandin E2-evoked increases in brown adipose tissue thermogenesis.
To elucidate central neural pathways contributing to the febrile component of the acute phase response to pyrogenic insult, I sought to determine whether activation of neurons in the rostral raphe pallidus (RPa) is required for the increase in brown adipose tissue (BAT) thermogenesis evoked by i.c.v. prostaglandin E(2) (PGE(2)) in urethane-chloralose-anesthetized, ventilated rats. BAT sympathetic nerve activity (SNA; +224% of control), BAT temperature (+1.8 degrees C), expired CO(2) (+1.3%), mean arterial pressure (+23 mm Hg), and heart rate (+73 beats per minute) were significantly increased after i.c.v. PGE(2) (2 microg). Microinjection of either the GABA(A) receptor agonist, muscimol (2 mM, 60 nl), or glycine (0.5M, 60 nl) into RPa resulted in a prompt reversal of the PGE(2)-evoked stimulation of BAT SNA, BAT thermogenesis and heart rate, with these variables returning to control levels prior to i.c.v. PGE(2) following the long-lasting, muscimol-induced inhibition of RPa neurons. In conclusion, activation of neurons in RPa, possibly BAT sympathetic premotor neurons, is essential for the increases in BAT SNA and BAT thermogenesis stimulated by i.c.v. administration of PGE(2). The increased heart rate likely contributing to an augmented cardiac output supporting the increased BAT thermogenesis in response to PGE(2) is also dependent on neurons in RPa. These results contribute to our understanding of central neural substrates for the augmented thermogenesis during fever.
Morrison
S F
SF
Neurological Sciences Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology*; D005917:Globus Pallidus / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D022722:Thermogenesis / Q000187:drug effects* / Q000502:physiology
D015232:Dinoprostone