title: Markers associated with testosterone enhancement of methamphetamine-induced striatal dopaminergic neurotoxicity.
abstract: Intact male CD-1 mice received an injection of testosterone propionate (TP--5 ug), progesterone (P--5 mg), the oil vehicle or remained untreated (control). At 24 hours after hormonal treatments the mice received an injection of methamphetamine (MA--40 mg/kg) and rectal temperatures were measured. At 5 days post-MA, assays were performed to assess effects of these treatments. Maximal increases in body temperatures, that were significantly greater than oil-treated controls, were obtained in TP-treated mice. At 5 days post-MA, maximal weight reductions were obtained with TP-treated mice, while P-treated mice showed no significant decrease between the pre- versus post-MA determinations. Striatal dopamine concentrations showed maximal reductions and heat-shock protein-70 maximal increases in the TP group, with both differing significantly as compared with all other groups. Protein levels of dopamine transporters were significantly decreased in P-treated mice, while vesicular monoamine transporter-2 was significantly decreased in TP-treated mice. Taken together, these results suggest that testosterone exacerbates the deleterious effects of MA within male mice as indicated by a number of markers related to neurotoxicity. The changes in markers as associated with this enhanced neurotoxicity suggest that TP may increase thermal/energy responses and/or oxidative stress to produce this effect.
authors.affiliation: Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH, USA.
authors.forename: A Blake
authors.initials: AB
authors.lastname: Buletko
authors.forename: Dean E
authors.initials: DE
authors.lastname: Dluzen
authors.forename: Janet L
authors.initials: JL
authors.lastname: McDermott
authors.forename: Altaf S
authors.initials: AS
authors.lastname: Darvesh
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Geldenhuys
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004357:Drug Synergism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D043343:Testosterone Propionate / Q000494:pharmacology*; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D018840:HSP70 Heat-Shock Proteins; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D008694:Methamphetamine; D004298:Dopamine; D043343:Testosterone Propionate