Loud noise enhances nigrostriatal dopamine toxicity induced by MDMA in mice.
The neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been intensely investigated due to the widespread abuse of this drug and its neurotoxic effects. In mice, MDMA neurotoxicity has been demonstrated for striatal dopamine (DA) terminals. However, the current literature has reported great variability in the effects induced by MDMA; this is partially due to changes in environmental conditions. For instance, elevated temperature and a crowded noisy environment markedly increase the neurotoxic effects induced by MDMA. The environmental factor loud noise is often present during ecstasy intake; however, only a few studies have analysed the consequence of a concomitant exposure to loud noise and ecstasy intake. In the present experimental work, we investigated whether nigrostriatal DA toxicity occurring after MDMA administration was potentiated in the presence of loud noise (100 dBA). We administered MDMA to C57/Black mice using a "binging" pattern for two durations of white noise exposure. We found a marked enhancement of MDMA toxicity (7.5 mg/Kg x4, 2 hours apart, i.p.) in the presence of white noise exposure lasting for at least 6 hours. The striatal damage was assessed by assaying DA levels as well as the loss of tyrosine hydroxylase (TH) and the increase in striatal glial fibrillary acidic protein (GFAP) immunohistochemistry. Since loud noise often accompanies ecstasy intake, the present findings call for more in-depth studies aimed at disclosing the fine mechanisms underlying this enhancement.
Department of Human Morphology and Applied Biology, University of Pisa, 55-56126 Pisa, Italy.
Marco
M
Gesi
Michela
M
Ferrucci
Mario
M
Giusiani
Paola
P
Lenzi
Gloria
G
Lazzeri
Maria G
MG
Alessandrì
Alessandra
A
Salvadorini
Federica
F
Fulceri
Antonio
A
Pellegrini
Francesco
F
Fornai
Antonio
A
Paparelli
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D006213:Hallucinogens / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009622:Noise / Q000009:adverse effects*; D019966:Substance-Related Disorders / Q000209:etiology / Q000473:pathology
D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine