Acetyl-L-carnitine provides effective in vivo neuroprotection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain

Neuroscience. 2009 Jan 23;158(2):514-23. doi: 10.1016/j.neuroscience.2008.10.041. Epub 2008 Oct 30.


3,4-Methylenedioximethamphetamine (MDMA, ecstasy) is a worldwide abused stimulant drug, with persistent neurotoxic effects and high prevalence among adolescents. The massive release of 5-HT from pre-synaptic storage vesicles induced by MDMA followed by monoamine oxidase B (MAO-B) metabolism, significantly increases oxidative stress at the mitochondrial level. l-Carnitine and its ester, acetyl-l-carnitine (ALC), facilitate the transport of long chain free fatty acids across the mitochondrial membrane enhancing neuronal anti-oxidative defense. Here, we show the potential of ALC against the neurotoxic effects of MDMA exposure. Adolescent male Wistar rats were assigned to four groups: control saline solution, isovolumetric to the MDMA solution, administered i.p.; MDMA (4x10 mg/kg MDMA, i.p.); ALC/MDMA (100 mg/kg 30 min of ALC prior to MDMA, i.p.) and ALC (100 mg/kg, i.p.). Rats were killed 2 weeks after exposure and brains were analyzed for lipid peroxidation, carbonyl formation, mitochondrial DNA (mtDNA) deletion and altered expression of the DNA-encoded subunits of the mitochondrial complexes I (NADH dehydrogenase, NDII) and IV (cytochrome c oxidase, COXI) from the respiratory chain. Levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were also assessed. The present work is the first to successfully demonstrate that pretreatment with ALC exerts effective neuroprotection against the MDMA-induced neurotoxicity at the mitochondrial level, reducing carbonyl formation, decreasing mtDNA deletion, improving the expression of the respiratory chain components and preventing the decrease of 5-HT levels in several regions of the rat brain. These results indicate potential benefits of ALC application in the prevention and treatment of neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine / therapeutic use*
  • Animals
  • Body Weight / drug effects
  • Brain / pathology
  • Brain / ultrastructure
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism
  • DNA, Mitochondrial / metabolism
  • Fever / chemically induced
  • Hallucinogens / toxicity*
  • Hydroxyindoleacetic Acid / metabolism
  • Lipid Peroxidation / drug effects
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria / drug effects
  • Mitochondrial Diseases / etiology*
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / pathology
  • Mitochondrial Diseases / prevention & control*
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • NADH Dehydrogenase / metabolism
  • Protein Carbonylation / drug effects
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism
  • Vitamin B Complex / therapeutic use*


  • DNA, Mitochondrial
  • Hallucinogens
  • Membrane Proteins
  • Vitamin B Complex
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Acetylcarnitine
  • Cyclooxygenase 1
  • Ptgs1 protein, rat
  • NADH Dehydrogenase
  • N-Methyl-3,4-methylenedioxyamphetamine