title: Endogenous activation of spinal 5-hydroxytryptamine (5-HT) receptors contributes to the thermoregulatory activation of brown adipose tissue.
abstract: Neurons in the rostral raphe pallidus (RPa) play an essential role in the regulation of sympathetically mediated metabolism and thermogenesis in brown adipose tissue (BAT). The presence of serotonergic neurons in the RPa that are retrogradely labeled following pseudorabies virus injections into BAT suggests that these neurons play a role in the regulation of BAT. In urethane/chloralose-anesthetized rats, whole body cooling decreased skin (-5.7 +/- 2.3 degrees C) and core (-1.3 +/- 0.2 degrees C) temperatures and resulted in an increase in BAT sympathetic nerve activity (SNA; +1,026 +/- 344% of baseline activity). Serial microinjections of the 5-hydroxytryptamine (5-HT) receptor antagonist, methysergide (1.2 nmol/site), but not saline vehicle, into the intermediolateral cell column (IML) in spinal segments T2-T5 markedly attenuated the cooling-evoked increase in BAT SNA (remaining area under the curve, AUC: 36 +/- 9% of naive cooling response). Microinjections of the 5-HT(1A) receptor antagonist, WAY-100635 (1.2 nmol/site), or the 5-HT(7) receptor antagonist, SB-269970 (1.2 nmol/site), into the T2-T5 IML also attenuated the cold-evoked increase in BAT SNA (remaining activity at peak inhibition: 47 +/- 8% and 39 +/- 12% of the initial cold-evoked response, respectively). The increases in BAT SNA evoked by microinjection of N-methyl-d-aspartate (NMDA) (12 pmol) or bicuculline (30 pmol) into the RPa were attenuated following microinjections of methysergide, but not saline vehicle, into the T2-T5 IML (NMDA remaining AUC, 64 +/- 13% of naive response; bicuculline remaining AUC, 52 +/- 5% of naive response). These results are consistent with our earlier demonstration of a potentiating effect of 5-HT within the IML on BAT SNA and indicate that activation of 5-HT(1A) and 5-HT(7) receptors in the spinal cord contributes to increases in BAT SNA and thermogenesis.
authors.affiliation: Oregon National Primate Research Center/OHSU, Beaverton, OR 97006, USA. maddench@ohsu.edu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Madden
authors.forename: Shaun F
authors.initials: SF
authors.lastname: Morrison
mesh_terms: D002001:Adipose Tissue, Brown / Q000294:innervation / Q000502:physiology*; D000818:Animals; D003086:Bacteriocin Plasmids; D001640:Bicuculline / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D008845:Microinjections; D016202:N-Methylaspartate / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D013904:Thoracic Vertebrae
chemical_list: D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D010636:Phenols; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D016202:N-Methylaspartate; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D008784:Methysergide; D001640:Bicuculline