Fonseca Raquel, Carvalho Rui A, Lemos Cristina, Sequeira Ana C, Pita Inês R, Carvalho Fábio, Silva Carlos D, Prediger Rui D S, Jarak Ivana, Cunha Rodrigo A, Fontes Ribeiro Carlos A, Köfalvi Attila, Pereira Frederico C
Laboratory of Pharmacology and Experimental Therapeutics/Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
CNC.IBILI, University of Coimbra, Coimbra, Portugal.
CNS Neurosci Ther. 2017 Feb;23(2):119-126. doi: 10.1111/cns.12649. Epub 2016 Oct 19.
We recently showed that a single high dose of methamphetamine (METH) induces a persistent frontal cortical monoamine depletion that is accompanied by helpless-like behavior in mice. However, brain metabolic alterations underlying both neurochemical and mood alterations remain unknown.
Herein, we aimed at characterizing frontal cortical metabolic alterations associated with early negative mood behavior triggered by METH. Adult C57BL/6 mice were injected with METH (30 mg/kg, i.p.), and their frontal cortical metabolic status was characterized after probing their mood and anxiety-related phenotypes 3 days postinjection.
Methamphetamine induced depressive-like behavior, as indicated by the decreased grooming time in the splash test and by a transient decrease in sucrose preference. At this time, METH did not alter anxiety-like behavior or motor functions. Depolarization-induced glucose uptake was reduced in frontocortical slices from METH-treated mice compared to controls. Consistently, astrocytic glucose transporter (GluT1) density was lower in the METH group. A proton high rotation magic angle spinning (HRMAS) spectroscopic approach revealed that METH induced a significant decrease in N-acetyl aspartate (NAA) and glutamate levels, suggesting that METH decreased neuronal glutamatergic function in frontal cortex.
We report, for the first time, that a single METH injection triggers early self-care and hedonic deficits and impairs frontal cortical energetics in mice.
我们最近发现，单次高剂量甲基苯丙胺（METH）会导致小鼠额叶皮质单胺持续耗竭，并伴有类似无助的行为。然而，神经化学和情绪改变背后的脑代谢变化仍不清楚。
在此，我们旨在表征与METH引发的早期负面情绪行为相关的额叶皮质代谢变化。给成年C57BL/6小鼠注射METH（30mg/kg，腹腔注射），在注射后3天探测其情绪和焦虑相关表型后，对其额叶皮质代谢状态进行表征。
甲基苯丙胺诱发了类似抑郁的行为，如在溅水试验中梳理毛发时间减少以及蔗糖偏好短暂降低所示。此时，METH并未改变类似焦虑的行为或运动功能。与对照组相比，METH处理小鼠的额叶皮质切片中去极化诱导的葡萄糖摄取减少。一致地，METH组星形胶质细胞葡萄糖转运体（GluT1）密度较低。质子高分辨率魔角旋转（HRMAS）光谱方法显示，METH导致N-乙酰天门冬氨酸（NAA）和谷氨酸水平显著降低，表明METH降低了额叶皮质神经元的谷氨酸能功能。
我们首次报道，单次注射METH会引发小鼠早期自我护理和享乐缺陷，并损害额叶皮质能量代谢。
