title: Involvement of the α(1D)-adrenergic receptor in methamphetamine-induced hyperthermia and neurotoxicity in rats.
abstract: Methamphetamine (METH) is a psychostimulant that damages nigrostriatal dopaminergic terminals, primarily by enhancing dopamine and glutamate release. α₁-adrenergic receptor (AR) subtype involved in METH-induced neurotoxicity in rats was investigated using selective α₁-AR antagonists. METH neurotoxicity was evaluated by (1) measuring body temperature; (2) determining tyrosine hydroxylase (TH) immunoreactivity levels; (3) examining levels of dopamine and its metabolites; and (4) assessing glial fibrillary acidic protein (GFAP) and microglial immunoreactivity in the striatum. METH caused a decrease in dopamine and TH levels and induced hyperthermia which is an exacerbating factor of METH neurotoxicity. Concurrently, METH increased GFAP expression and the number of activated microglia. Pretreatment with prazosin, a nonselective α₁-AR antagonist, completely abolished METH-induced decrease in both dopamine and TH and caused a partial reduction in hyperthermia. Prazosin also prevented METH-induced increase in both GFAP expression and the number of activated microglia. In vivo microdialysis analysis revealed that prazosin, however, does not alter the METH-induced dopamine release in the striatum. The neuroprotective effects of prazosin could be mimicked by a selective α(1D) antagonist, BMY 7378, but not by selective α(1A) or α(1B) antagonists. These results suggest that the α(1D)-AR is involved in METH-induced hyperthermia and neurotoxicity in rats.
authors.affiliation: Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi Ward, Tokyo 173-8605, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Kikuchi-Utsumi
authors.forename: Mami
authors.initials: M
authors.lastname: Ishizaka
authors.forename: Nobuko
authors.initials: N
authors.lastname: Matsumura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watabe
authors.forename: Koji
authors.initials: K
authors.lastname: Aoyama
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sasakawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakaki
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology*; D006979:Hyperthermia, Induced / Q000379:methods; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D008694:Methamphetamine