title: Cocaine potentiates MDMA-induced oxidative stress but not dopaminergic neurotoxicity in mice: implications for the pathogenesis of free radical-induced neurodegenerative disorders.
abstract: BACKGROUND
  The drugs of abuse 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") and cocaine both increase the generation of free radicals, and in the case of MDMA, this increase in oxidative stress is involved in the dopaminergic neurotoxicity produced by the drug in mice. Oxidative stress processes are also involved in the pathogenesis of several neurodegenerative diseases.
  
  
  OBJECTIVE
  We aimed to determine the consequences of the combined administration of MDMA and cocaine on oxidative stress and dopaminergic neurotoxicity.
  
  
  METHODS
  Mice received MDMA (20 mg/kg, i.p.; two doses separated by 3 h) followed by cocaine 1, 3, 6, or 24 h after the second MDMA dose. Mice were killed between 1 h and 7 days after cocaine injection.
  
  
  RESULTS
  MDMA decreased dopamine transporter density and dopamine concentration 7 days later. Cocaine did not alter this neurotoxicity. MDMA produced an increase in the concentration of 2,3-dihydroxybenzoic acid in striatal microdialysis samples and an increase in lipid peroxidation in the striatum which were potentiated by cocaine. MDMA and cocaine given together also increased nitrate and 3-nitrotyrosine levels compared with either drug given alone. On the other hand, MDMA increased superoxide dismutase activity and decreased catalase activity, changes which were prevented by cocaine administration. In addition, cocaine administration produced an increase in glutathione peroxidase (GPx) activity in both saline-treated and MDMA-treated mice.
  
  
  CONCLUSIONS
  Cocaine potentiates MDMA-induced oxidative stress but does not produce an increase in the neurotoxicity produced by MDMA, and this lack of potentiation may involve an increase in GPx activity.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid, 28040, Spain.
authors.forename: Ines
authors.initials: I
authors.lastname: Peraile
authors.forename: Noelia
authors.initials: N
authors.lastname: Granado
authors.forename: Elisa
authors.initials: E
authors.lastname: Torres
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Gutiérrez-López
authors.forename: Rosario
authors.initials: R
authors.lastname: Moratalla
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Colado
authors.forename: Esther
authors.initials: E
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D013997:Time Factors
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005609:Free Radicals; D005979:Glutathione Peroxidase; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine