Peripheral N-methyl-D-aspartate receptor activation contributes to monosodium glutamate-induced headache but not nausea behaviours in rats

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  • Tarique Benbow, University of British Columbia, Canada
  • Felisha Teja, University of British Columbia, Canada
  • Afrooz Sheikhi, University of British Columbia, Canada
  • Fernando G Exposto
  • Peter Svensson
  • Brian E Cairns, University of British Columbia, Canada

Monosodium glutamate induces behaviors thought to reflect headache and nausea in rats. We explored the effects of the N-methyl-D-aspartate receptor antagonist (2R)-amino-5-phosphonovaleric acid, the inotropic glutamate receptor antagonist kynurenic acid, and the CGRP receptor antagonist olcegepant, on monosodium glutamate-induced increases in nocifensive, headache-like and nausea behaviours. Effects of these antagonists on motor function were examined with a rotarod. The effect of the dopamine receptor antagonist metoclopramide and the serotonin 3 receptor antagonist ondansetron on nausea behaviour was also assessed. (2R)-amino-5-phosphonovaleric acid, and to a lesser extent, kynurenic acid and olcegepant, reduced nocifensive and headache-like behaviours evoked by monosodium glutamate. No alteration in motor function by (2R)-amino-5-phosphonovaleric acid, kynurenic acid or olcegepant was observed. No sex-related differences in the effectiveness of these agents were identified. Nausea behaviour was significantly more pronounced in male than in female rats. Olcegepant, ondansetron and metoclopramide ameliorated this nausea behaviour in male rats. Ondansetron and metoclopramide also reduced headache-like behaviour in male rats. These findings suggest that peripheral N-methyl-D-aspartate receptor activation underlies monosodium glutamate-induced headache-like behaviour but does not mediate the nausea behaviour in rats.

Original languageEnglish
Article number13894
JournalScientific Reports
Number of pages12
Publication statusPublished - Aug 2022

Bibliographical note

© 2022. The Author(s).

    Research areas

  • Amino Acids, Animals, Aspartic Acid, Female, Glutamic Acid, Headache, Kynurenic Acid/pharmacology, Male, Metoclopramide, Nausea/chemically induced, Ondansetron/pharmacology, Rats, Receptors, N-Methyl-D-Aspartate, Sodium Glutamate

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