a Department of Nutrition , Universidade Federal de Pernambuco , Recife , PE 50670901 , Brazil.
Nutr Neurosci. 2019 Jun;22(6):435-443. doi: 10.1080/1028415X.2017.1398301. Epub 2017 Nov 10.
The route of administration is an important factor in determining the action of some drugs. We previously demonstrated that subcutaneous monosodium glutamate (MSG) accelerated cortical spreading depression (CSD) in the rat and that treadmill exercise attenuated this effect. This study evaluated whether other routes of administration exert the same action by testing orogastric (gavage) and topical cortical MSG administration in treadmill-exercised and sedentary rats. Additionally, in the orogastric treatment we tested anxiety-like behavior.
Exercised and sedentary rats received per gavage water or MSG (1 or 2 g/kg) daily from postnatal (P) day 7 to 27. Behavioral tests (open field and elevated plus-maze) occurred at P53 ± 3. At P56 ± 3, we analyzed CSD parameters (velocity, amplitude, and duration of the negative potential change). Other three groups of rats received an MSG solution (25, 50 or 75 mg/ml) topically to the intact dura mater during CSD recording.
MSG-gavage increased anxiety-like behavior and the CSD velocities compared with water-treated controls (P < 0.05). Exercise decelerated CSD. In contrast to gavage, which accelerated CSD, topical MSG dose-dependently and reversibly impaired CSD propagation, reduced CSD amplitude and increased CSD duration (P < 0.05).
The exercise-dependent attenuation of the effects of MSG confirms our previous results in rats treated subcutaneously with MSG. CSD results suggest two distinct mechanisms for gavage and topical MSG administration. Additionally, data suggest that exercise can help protect the developing and adult brain against the deleterious actions of MSG.
给药途径是决定某些药物作用的重要因素。我们之前的研究表明，皮下注射单谷氨酸钠（MSG）可加速大鼠皮质扩散性抑制（CSD），而跑步机运动则可减弱这种作用。本研究通过测试经口（灌胃）和皮质局部 MSG 给药，评估其他给药途径是否具有相同的作用，同时在跑步机运动和久坐的大鼠中进行。此外，在经口治疗中，我们测试了焦虑样行为。
从出生后（P）第 7 天至 27 天，运动和久坐的大鼠每天通过灌胃给予水或 MSG（1 或 2 g/kg）。行为测试（旷场和高架十字迷宫）在 P53 ± 3 时进行。在 P56 ± 3 时，我们分析了 CSD 参数（负电势变化的速度、幅度和持续时间）。另外三组大鼠在 CSD 记录期间，将 MSG 溶液（25、50 或 75mg/ml）局部涂于完整硬脑膜。
与水对照组相比，MSG 灌胃增加了焦虑样行为和 CSD 速度（P<0.05）。运动使 CSD 减速。与加速 CSD 的灌胃相反，局部 MSG 呈剂量依赖性和可逆性地损害 CSD 传播，降低 CSD 幅度并增加 CSD 持续时间（P<0.05）。
运动对 MSG 影响的衰减作用证实了我们之前在皮下注射 MSG 的大鼠中得到的结果。CSD 结果表明，灌胃和局部 MSG 给药有两种不同的机制。此外，数据表明，运动可以帮助保护发育中和成年期的大脑免受 MSG 的有害作用。
