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

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
CNS Neurosci Ther. 2016-10-19; 23(2): 119-126
DOI: 10.1111/cns.12649

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INTRODUCTION: 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.
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.
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

Auteurs Bordeaux Neurocampus