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