title: σ Receptor antagonist attenuation of methamphetamine-induced neurotoxicity is correlated to body temperature modulation.
abstract: BACKGROUND
  Methamphetamine (METH) causes hyperthermia and dopaminergic neurotoxicity in the rodent striatum. METH interacts with σ receptors and σ receptor antagonists normally mitigate METH-induced hyperthermia and dopaminergic neurotoxicity. The present study was undertaken because in two experiments, pretreatment with σ receptor antagonists failed to attenuate METH-induced hyperthermia in mice. This allowed us to determine whether the ability of σ receptor antagonists (AZ66 and AC927) to mitigate METH-induced neurotoxicity depends upon their ability to modulate METH-induced hyperthermia.
  
  
  METHODS
  Mice were treated using a repeated dosing paradigm and body temperatures recorded. Striatal dopamine was measured one week post-treatment.
  
  
  RESULTS
  The data indicate that the ability of σ receptor antagonists to attenuate METH-induced dopaminergic neurotoxicity is linked to their ability to block METH-induced hyperthermia.
  
  
  CONCLUSIONS
  The ability of σ receptor antagonists to mitigate METH-induced hyperthermia may contribute to its neuroprotective actions.
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, 1 Medical Center Drive, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Robson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Seminerio
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McCurdy
authors.forename: Andrew
authors.initials: A
authors.lastname: Coop
authors.forename: Rae R
authors.initials: RR
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D010070:Oxalates / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017480:Receptors, sigma / Q000037:antagonists & inhibitors*
chemical_list: C584010:3-(4-(4-cyclohexylpiperazine-1-yl)pentyl)-6-fluorobenzo(d)thiazole-2(3H)-one; D052160:Benzothiazoles; D015259:Dopamine Agents; C470324:N-phenethylpiperidine oxalate; D010070:Oxalates; D010879:Piperazines; D010880:Piperidines; D017480:Receptors, sigma; D008694:Methamphetamine; D004298:Dopamine