title: Adolescent exposure to MDMA induces dopaminergic toxicity in substantia nigra and potentiates the amyloid plaque deposition in the striatum of APPswe/PS1dE9 mice.
abstract: MDMA is one of the most used drugs by adolescents and its consumption has been associated with many psychobiological problems, among them psychomotor problems. Moreover, some authors described that early exposure to MDMA may render the dopaminergic neurons more vulnerable to the effects of future neurotoxic insults. Alzheimer disease (AD) is the main cause of dementia in the elderly and a percentage of the patients have predisposition to suffer nigrostriatal alterations, developing extrapyramidal signs. Nigrostriatal dysfunction in the brain of aged APPswe/PS1dE9 (APP/PS1), a mouse model of familiar AD (FAD), has also been described. The aim of the present study was to investigate the consequences of adolescent exposure to MDMA in APP/PS1 mice, on nigrostriatal function on early adulthood. We used a MDMA schedule simulating weekend binge abuse of this substance. Our MDMA schedule produced a genotype-independent decrease in dopaminergic neurons in the substantia nigra that remained at least 3months. Shortly after the injury, wild-type animals showed a decrease in the locomotor activity and apparent DA depletion in striatum, however in the APP/PS1 mice neither the locomotor activity nor the DA levels were modified, but a reduction in dopamine transporter (DAT) expression and a higher levels of oxidative stress were observed. We found that these disturbances are age-related characteristics that this APP/PS1 mice develops spontaneously much later. Therefore, MDMA administration seems to anticipate the striatal dopaminergic dysfunction in this FAD model. The most important outcome lies in a potentiation, by MDMA, of the amyloid beta deposition in the striatum.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry (Pharmacology Section) and Biomedicine Institute, University of Barcelona (IBUB), Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Abad
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry (Pharmacology Section) and Biomedicine Institute, University of Barcelona (IBUB), Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Ramon
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry (Pharmacology Section) and Biomedicine Institute, University of Barcelona (IBUB), Spain.
authors.forename: David
authors.initials: D
authors.lastname: Pubill
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry (Pharmacology Section) and Biomedicine Institute, University of Barcelona (IBUB), Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Camarasa
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry (Pharmacology Section) and Biomedicine Institute, University of Barcelona (IBUB), Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Spain. Electronic address: camins@ub.edu.
authors.forename: Antonio
authors.initials: A
authors.lastname: Camins
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutic Chemistry (Pharmacology Section) and Biomedicine Institute, University of Barcelona (IBUB), Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Escubedo
mesh_terms: D000293:Adolescent; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008995:Monoamine Oxidase / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D058225:Plaque, Amyloid / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012741:Sexual Maturation; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D050505:Mutant Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011993:Recombinant Fusion Proteins; D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: 3.4-Methylenedioxymethamphetamine; APPswe/PS1dE9 mice; Amyloid plaques; Dopaminergic dysfunction; Striatum