Endogenous activation of spinal 5-hydroxytryptamine (5-HT) receptors contributes to the thermoregulatory activation of brown adipose tissue

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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°C) and core (-1.3 ± 0.2°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-HT1A receptor antagonist, WAY-100635 (1.2 nmol/site), or the 5-HT7 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-HT1A and 5-HT7 receptors in the spinal cord contributes to increases in BAT SNA and thermogenesis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Brown Adipose Tissue
Serotonin Receptors
Microinjections
Area Under Curve
Methysergide
Bicuculline
Thermogenesis
N-Methylaspartate
Serotonin 5-HT1 Receptor Antagonists
Suid Herpesvirus 1
Serotonergic Neurons
Neurons
Chloralose
Serotonin Antagonists
Receptor, Serotonin, 5-HT1A
Urethane
Serotonin
Spinal Cord
Skin
Injections

Keywords

  • Metabolism
  • Raphe
  • Serotonin
  • Sympathetic premotor neurons
  • Thermoregulation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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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°C) and core (-1.3 ± 0.2°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-HT1A receptor antagonist, WAY-100635 (1.2 nmol/site), or the 5-HT7 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-HT1A and 5-HT7 receptors in the spinal cord contributes to increases in BAT SNA and thermogenesis.",
keywords = "Metabolism, Raphe, Serotonin, Sympathetic premotor neurons, Thermoregulation",
author = "Madden, {Christopher (Chris)} and Shaun Morrison",
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T1 - Endogenous activation of spinal 5-hydroxytryptamine (5-HT) receptors contributes to the thermoregulatory activation of brown adipose tissue

AU - Madden, Christopher (Chris)

AU - Morrison, Shaun

PY - 2010/3

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N2 - 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°C) and core (-1.3 ± 0.2°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-HT1A receptor antagonist, WAY-100635 (1.2 nmol/site), or the 5-HT7 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-HT1A and 5-HT7 receptors in the spinal cord contributes to increases in BAT SNA and thermogenesis.

AB - 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°C) and core (-1.3 ± 0.2°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-HT1A receptor antagonist, WAY-100635 (1.2 nmol/site), or the 5-HT7 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-HT1A and 5-HT7 receptors in the spinal cord contributes to increases in BAT SNA and thermogenesis.

KW - Metabolism

KW - Raphe

KW - Serotonin

KW - Sympathetic premotor neurons

KW - Thermoregulation

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U2 - 10.1152/ajpregu.00614.2009

DO - 10.1152/ajpregu.00614.2009

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VL - 298

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 3

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