Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, V6T 1Z3, Canada.
Section for Orofacial Pain and Jaw Function, Department of Dentistry and Oral Health, Aarhus University, Vennelyst Boulevard 9, 8000, Aarhus C, Denmark.
Sci Rep. 2022 Aug 16;12(1):13894. doi: 10.1038/s41598-022-18290-w.
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.
谷氨酸单钠可诱导大鼠产生头痛和恶心的行为，我们研究了 NMDA 受体拮抗剂 (2R)-氨基-5-膦戊酸、促代谢型谷氨酸受体拮抗剂 kynurenic 酸和 CGRP 受体拮抗剂 olcegepant 对谷氨酸单钠诱导的伤害性行为、类头痛和恶心行为的影响。用转棒实验检测这些拮抗剂对运动功能的影响。还评估了多巴胺受体拮抗剂甲氧氯普胺和 5-羟色胺 3 受体拮抗剂昂丹司琼对恶心行为的影响。(2R)-氨基-5-膦戊酸，以及在较小程度上，kynurenic 酸和 olcegepant，可减少谷氨酸单钠引起的伤害性行为和类头痛行为。(2R)-氨基-5-膦戊酸、kynurenic 酸或 olcegepant 对运动功能没有改变。未发现这些药物在有效性上存在性别差异。雄性大鼠的恶心行为比雌性大鼠更为明显。Olcegepant、昂丹司琼和甲氧氯普胺可改善雄性大鼠的这种恶心行为。昂丹司琼和甲氧氯普胺还可减少雄性大鼠的类头痛行为。这些发现表明，外周 NMDA 受体激活是谷氨酸单钠诱导的类头痛行为的基础，但不能介导大鼠的恶心行为。
