Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT1A receptor activation in raphe pallidus

Clarissa M.D. Mota, Luiz G.S. Branco, Shaun F. Morrison, Christopher J. Madden

Research output: Contribution to journalArticle

Abstract

Aim: Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter and hormone, modulates many physiological functions including body temperature. We investigated neural mechanisms involved in the inhibition of brown adipose tissue (BAT) sympathetic nerve activity (SNA) and BAT thermogenesis evoked by 5-HT. Methods: Electrophysiological recordings, intravenous (iv) injections and nanoinjections in the brains of anaesthetized rats. Results: Cooling-evoked increases in BAT SNA were inhibited by the intra-rostral raphé pallidus (rRPa) and the iv administration of the 5-HT1A receptor agonist, 8-OH-DPAT or 5-HT. The intra-rRPa 5-HT, the intra-rRPa and the iv 8-OH-DPAT, but not the iv 5-HT-induced inhibition of BAT SNA were prevented by nanoinjection of a 5-HT1A receptor antagonist in the rRPa. The increase in BAT SNA evoked by nanoinjection of NMDA in the rRPa was not inhibited by iv 5-HT, indicating that iv 5-HT does not inhibit BAT SNA by acting in the rRPa or in the sympathetic pathway distal to the rRPa. In contrast, under a warm condition, blockade of 5HT1A receptors in the rRPa increased BAT SNA and BAT thermogenesis, suggesting that endogenous 5-HT in the rRPa contributes to the suppression of BAT SNA and BAT thermogenesis. The increases in BAT SNA and BAT thermogenesis evoked by nanoinjection of NMDA in the dorsomedial hypothalamus (DMH) were inhibited by iv 5-HT, but those following bicuculline nanoinjection in the DMH were not inhibited. Conclusions: The systemic 5-HT-induced inhibition of BAT SNA requires a GABAergic inhibition of BAT sympathoexcitatory neurones in the DMH. In addition, during warming, 5-HT released endogenously in rRPa inhibits BAT SNA.

Original languageEnglish (US)
Article numbere13401
JournalActa Physiologica
DOIs
StateAccepted/In press - Jan 1 2019

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Brown Adipose Tissue
gamma-Aminobutyric Acid
Hypothalamus
Serotonin
Thermogenesis
8-Hydroxy-2-(di-n-propylamino)tetralin
Receptor, Serotonin, 5-HT1A
N-Methylaspartate
Serotonin 5-HT1 Receptor Antagonists
Serotonin 5-HT1 Receptor Agonists
Bicuculline
Body Temperature
Intravenous Injections
Intravenous Administration

Keywords

  • 5-hydroxytryptamine
  • brown adipose tissue
  • hypothalamus
  • raphé pallidus
  • thermoregulation

ASJC Scopus subject areas

  • Physiology

Cite this

@article{b2a481ba19714246bc687f218a394486,
title = "Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT1A receptor activation in raphe pallidus",
abstract = "Aim: Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter and hormone, modulates many physiological functions including body temperature. We investigated neural mechanisms involved in the inhibition of brown adipose tissue (BAT) sympathetic nerve activity (SNA) and BAT thermogenesis evoked by 5-HT. Methods: Electrophysiological recordings, intravenous (iv) injections and nanoinjections in the brains of anaesthetized rats. Results: Cooling-evoked increases in BAT SNA were inhibited by the intra-rostral raph{\'e} pallidus (rRPa) and the iv administration of the 5-HT1A receptor agonist, 8-OH-DPAT or 5-HT. The intra-rRPa 5-HT, the intra-rRPa and the iv 8-OH-DPAT, but not the iv 5-HT-induced inhibition of BAT SNA were prevented by nanoinjection of a 5-HT1A receptor antagonist in the rRPa. The increase in BAT SNA evoked by nanoinjection of NMDA in the rRPa was not inhibited by iv 5-HT, indicating that iv 5-HT does not inhibit BAT SNA by acting in the rRPa or in the sympathetic pathway distal to the rRPa. In contrast, under a warm condition, blockade of 5HT1A receptors in the rRPa increased BAT SNA and BAT thermogenesis, suggesting that endogenous 5-HT in the rRPa contributes to the suppression of BAT SNA and BAT thermogenesis. The increases in BAT SNA and BAT thermogenesis evoked by nanoinjection of NMDA in the dorsomedial hypothalamus (DMH) were inhibited by iv 5-HT, but those following bicuculline nanoinjection in the DMH were not inhibited. Conclusions: The systemic 5-HT-induced inhibition of BAT SNA requires a GABAergic inhibition of BAT sympathoexcitatory neurones in the DMH. In addition, during warming, 5-HT released endogenously in rRPa inhibits BAT SNA.",
keywords = "5-hydroxytryptamine, brown adipose tissue, hypothalamus, raph{\'e} pallidus, thermoregulation",
author = "Mota, {Clarissa M.D.} and Branco, {Luiz G.S.} and Morrison, {Shaun F.} and Madden, {Christopher J.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/apha.13401",
language = "English (US)",
journal = "Acta Physiologica",
issn = "1748-1708",

}

TY - JOUR

T1 - Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT1A receptor activation in raphe pallidus

AU - Mota, Clarissa M.D.

AU - Branco, Luiz G.S.

AU - Morrison, Shaun F.

AU - Madden, Christopher J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Aim: Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter and hormone, modulates many physiological functions including body temperature. We investigated neural mechanisms involved in the inhibition of brown adipose tissue (BAT) sympathetic nerve activity (SNA) and BAT thermogenesis evoked by 5-HT. Methods: Electrophysiological recordings, intravenous (iv) injections and nanoinjections in the brains of anaesthetized rats. Results: Cooling-evoked increases in BAT SNA were inhibited by the intra-rostral raphé pallidus (rRPa) and the iv administration of the 5-HT1A receptor agonist, 8-OH-DPAT or 5-HT. The intra-rRPa 5-HT, the intra-rRPa and the iv 8-OH-DPAT, but not the iv 5-HT-induced inhibition of BAT SNA were prevented by nanoinjection of a 5-HT1A receptor antagonist in the rRPa. The increase in BAT SNA evoked by nanoinjection of NMDA in the rRPa was not inhibited by iv 5-HT, indicating that iv 5-HT does not inhibit BAT SNA by acting in the rRPa or in the sympathetic pathway distal to the rRPa. In contrast, under a warm condition, blockade of 5HT1A receptors in the rRPa increased BAT SNA and BAT thermogenesis, suggesting that endogenous 5-HT in the rRPa contributes to the suppression of BAT SNA and BAT thermogenesis. The increases in BAT SNA and BAT thermogenesis evoked by nanoinjection of NMDA in the dorsomedial hypothalamus (DMH) were inhibited by iv 5-HT, but those following bicuculline nanoinjection in the DMH were not inhibited. Conclusions: The systemic 5-HT-induced inhibition of BAT SNA requires a GABAergic inhibition of BAT sympathoexcitatory neurones in the DMH. In addition, during warming, 5-HT released endogenously in rRPa inhibits BAT SNA.

AB - Aim: Serotonin (5-hydroxytryptamine, 5-HT), an important neurotransmitter and hormone, modulates many physiological functions including body temperature. We investigated neural mechanisms involved in the inhibition of brown adipose tissue (BAT) sympathetic nerve activity (SNA) and BAT thermogenesis evoked by 5-HT. Methods: Electrophysiological recordings, intravenous (iv) injections and nanoinjections in the brains of anaesthetized rats. Results: Cooling-evoked increases in BAT SNA were inhibited by the intra-rostral raphé pallidus (rRPa) and the iv administration of the 5-HT1A receptor agonist, 8-OH-DPAT or 5-HT. The intra-rRPa 5-HT, the intra-rRPa and the iv 8-OH-DPAT, but not the iv 5-HT-induced inhibition of BAT SNA were prevented by nanoinjection of a 5-HT1A receptor antagonist in the rRPa. The increase in BAT SNA evoked by nanoinjection of NMDA in the rRPa was not inhibited by iv 5-HT, indicating that iv 5-HT does not inhibit BAT SNA by acting in the rRPa or in the sympathetic pathway distal to the rRPa. In contrast, under a warm condition, blockade of 5HT1A receptors in the rRPa increased BAT SNA and BAT thermogenesis, suggesting that endogenous 5-HT in the rRPa contributes to the suppression of BAT SNA and BAT thermogenesis. The increases in BAT SNA and BAT thermogenesis evoked by nanoinjection of NMDA in the dorsomedial hypothalamus (DMH) were inhibited by iv 5-HT, but those following bicuculline nanoinjection in the DMH were not inhibited. Conclusions: The systemic 5-HT-induced inhibition of BAT SNA requires a GABAergic inhibition of BAT sympathoexcitatory neurones in the DMH. In addition, during warming, 5-HT released endogenously in rRPa inhibits BAT SNA.

KW - 5-hydroxytryptamine

KW - brown adipose tissue

KW - hypothalamus

KW - raphé pallidus

KW - thermoregulation

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U2 - 10.1111/apha.13401

DO - 10.1111/apha.13401

M3 - Article

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JO - Acta Physiologica

JF - Acta Physiologica

SN - 1748-1708

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