title: Effect of crowding, temperature and age on glia activation and dopaminergic neurotoxicity induced by MDMA in the mouse brain.
abstract: 3,4-methylenedyoxymethamphetamine (MDMA or "ecstasy"), a recreational drug of abuse, can induce glia activation and dopaminergic neurotoxicity. Since MDMA is often consumed in crowded environments featuring high temperatures, we studied how these factors influenced glia activation and dopaminergic neurotoxicity induced by MDMA. C57BL/6J adolescent (4 weeks old) and adult (12 weeks old) mice received MDMA (4×20mg/kg) in different conditions: 1) while kept 1, 5, or 10×cage at room temperature (21°C); 2) while kept 5×cage at either room (21°C) or high (27°C) temperature. After the last MDMA administration, immunohistochemistry was performed in the caudate-putamen for CD11b and GFAP, to mark microglia and astroglia, and in the substantia nigra pars compacta for tyrosine hydroxylase, to mark dopaminergic neurons. MDMA induced glia activation and dopaminergic neurotoxicity, compared with vehicle administration. Crowding (5 or 10 mice×cage) amplified MDMA-induced glia activation (in adult and adolescent mice) and dopaminergic neurotoxicity (in adolescent mice). Conversely, exposure to a high environmental temperature (27°C) potentiated MDMA-induced glia activation in adult and adolescent mice kept 5×cage, but not dopaminergic neurotoxicity. Crowding and exposure to a high environmental temperature amplified MDMA-induced hyperthermia, and a positive correlation between body temperature and activation of either microglia or astroglia was found in adult and adolescent mice. These results provide further evidence that the administration setting influences the noxious effects of MDMA in the mouse brain. However, while crowding amplifies both glia activation and dopaminergic neurotoxicity, a high environmental temperature exacerbates glia activation only.
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy. Electronic address: luciafrau79@hotmail.com.
authors.forename: Lucia
authors.initials: L
authors.lastname: Frau
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy. Electronic address: nicola.simola@gmail.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Simola
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy. Electronic address: fra8714@hotmail.it.
authors.forename: Pier Francesca
authors.initials: PF
authors.lastname: Porceddu
authors.affiliation: Department of Biomedical Sciences, Section of Neuropsychopharmacology, University of Cagliari, Via Ospedale 72, 09124, Cagliari, Italy; CNR, Institute of Neuroscience, Cagliari, Italy. Electronic address: morelli@unica.it.
authors.forename: Micaela
authors.initials: M
authors.lastname: Morelli
mesh_terms: D000375:Aging / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D003441:Crowding / Q000523:psychology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006213:Hallucinogens / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology / Q000523:psychology; D013696:Temperature; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D006213:Hallucinogens; D014446:Tyrosine 3-Monooxygenase; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine
keywords: Aggregation; Cage density; Ecstasy; Glia; Hyperthermia; Neurodegeneration