Methamphetamine Induces Anhedonic-Like Behavior and Impairs Frontal Cortical Energetics in Mice

甲基苯丙胺诱导小鼠快感缺乏样行为并损害额叶皮质能量

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作者:Raquel Fonseca, Rui A Carvalho, Cristina Lemos, Ana C Sequeira, Inês R Pita, Fábio Carvalho, Carlos D Silva, Rui D S Prediger, Ivana Jarak, Rodrigo A Cunha, Carlos A Fontes Ribeiro, Attila Köfalvi, Frederico C Pereira

Aims

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.

Conclusions

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.

Results

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. Conclusions: 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.

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