title: Mephedrone, an abused psychoactive component of 'bath salts' and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum.
abstract: Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine with close structural analogy to substituted amphetamines and cathinone derivatives. Abuse of mephedrone has increased dramatically in recent years and has become a significant public health problem in the United States and Europe. Unfortunately, very little information is available on the pharmacological and neurochemical actions of mephedrone. In light of the proven abuse potential of mephedrone and considering its similarity to methamphetamine and methcathinone, it is particularly important to know if mephedrone shares with these agents an ability to cause damage to dopamine nerve endings of the striatum. Accordingly, we treated mice with a binge-like regimen of mephedrone (4 × 20 or 40 mg/kg) and examined the striatum for evidence of neurotoxicity 2 or 7 days after treatment. While mephedrone caused hyperthermia and locomotor stimulation, it did not lower striatal levels of dopamine, tyrosine hydroxylase or the dopamine transporter under any of the treatment conditions used presently. Furthermore, mephedrone did not cause microglial activation in striatum nor did it increase glial fibrillary acidic protein levels. Taken together, these surprising results suggest that mephedrone, despite its numerous mechanistic overlaps with methamphetamine and the cathinone derivatives, does not cause neurotoxicity to dopamine nerve endings of the striatum.
authors.affiliation: Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Angoa-Pérez
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kane
authors.forename: Dina M
authors.initials: DM
authors.lastname: Francescutti
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Sykes
authors.forename: Mrudang M
authors.initials: MM
authors.lastname: Shah
authors.forename: Abiy M
authors.initials: AM
authors.lastname: Mohammed
authors.forename: David M
authors.initials: DM
authors.lastname: Thomas
authors.forename: Donald M
authors.initials: DM
authors.lastname: Kuhn
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology*; D005260:Female; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009411:Nerve Endings / Q000187:drug effects*; D009457:Neuroglia / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D008694:Methamphetamine; C548233:mephedrone; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine