Glutamate receptors in the raphe pallidus mediate brown adipose tissue thermogenesis evoked by activation of dorsomedial hypothalamic neurons

Wei Hua Cao, Shaun F. Morrison

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Disinhibition of DMH neurons with the GABAA receptor antagonist, bicuculline, increases heart rate (HR) and augments both brown adipose tissue sympathetic nerve activity (BAT SNA) and renal SNA (RSNA) contributing to the evoked increases in BAT thermogenesis and arterial pressure (AP). We determined the role of glutamate receptor activation in the rostral raphe pallidus (RPa) in mediating the sympathoexcitatory responses in HR, BAT SNA and RSNA following disinhibition of DMH neurons in urethane/chloralose anesthetized, artificially ventilated rats. Microinjections of either the selective NMDA receptor agonist, NMDA, or the selective non-NMDA receptor agonist, kainic acid (KA), into the RPa produced increases in BAT SNA (peak: +502% and +408% of control, respectively) and BAT temperature (peak: +0.6 °C and +1.0 °C) accompanied by rises in HR (peak: +38 and +63 bpm), RSNA (peak: +57% and +58% of control) and MAP (peak: +12 and 15 mmHg). These responses were reversed by subsequent microinjection into RPa of the respective selective glutamate receptor antagonists, AP5 and CNQX. Microinjections of the non-selective glutamate receptor antagonist, kynurenic acid (Kyn), the NMDA receptor antagonist, AP5, or the non-NMDA receptor antagonist, CNQX, were effective in reversing the increases in BAT SNA (for Kyn, from peak of +419% of control to +9% of control) and BAT temperature, but not those in HR, MAP or RSNA (for Kyn, from peak of +143% of control to +124% of control) evoked by unilateral microinjection of bicuculline into the DMH. These results indicate that both NMDA and non-NMDA glutamate receptors in the RPa play a significant role in mediating the excitatory synaptic transmission producing the activation of BAT thermogenesis following disinhibition of DMH neurons. Glutamate receptors in the RPa may not be important for transmitting cardiovascular responses induced by activation of the DMH neurons.

Original languageEnglish (US)
Pages (from-to)426-437
Number of pages12
JournalNeuropharmacology
Volume51
Issue number3
DOIs
StatePublished - Sep 1 2006

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Keywords

  • Energy expenditure
  • Excitatory amino acid
  • Sympathetic nerve activity
  • Thermoregulation

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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