title: Methamphetamine Induces Anhedonic-Like Behavior and Impairs Frontal Cortical Energetics in Mice.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics/Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: CNC.IBILI, University of Coimbra, Coimbra, Portugal.|CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: Rui A
authors.initials: RA
authors.lastname: Carvalho
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lemos
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics/Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Sequeira
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics/Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Inês R
authors.initials: IR
authors.lastname: Pita
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Fábio
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics/Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Silva
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC, Florianópolis, Brazil.
authors.forename: Rui D S
authors.initials: RD
authors.lastname: Prediger
authors.affiliation: CNC.IBILI, University of Coimbra, Coimbra, Portugal.|CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jarak
authors.affiliation: CNC.IBILI, University of Coimbra, Coimbra, Portugal.|CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: 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.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Fontes Ribeiro
authors.affiliation: CNC.IBILI, University of Coimbra, Coimbra, Portugal.|CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
authors.forename: Attila
authors.initials: A
authors.lastname: Köfalvi
authors.affiliation: 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.
authors.forename: Frederico C
authors.initials: FC
authors.lastname: Pereira
mesh_terms: D059445:Anhedonia / Q000187:drug effects*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001930:Brain Injuries / Q000139:chemically induced* / Q000473:pathology*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006120:Grooming / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; C495689:Slc2a3 protein, mouse; D001224:Aspartic Acid; D018698:Glutamic Acid; D008694:Methamphetamine; C000179:N-acetylaspartate; D005947:Glucose
keywords: Depressive-like behavior; Frontal cortex; Glucose metabolism; Methamphetamine