Testosterone enhances dopamine depletion by methamphetamine in male, but not female, mice.
We examined the effects of varying concentrations of testosterone propionate (T) treatment within intact and gonadectomized male and female mice with regard to its capacity to alter striatal dopamine (DA) depletion in response to a neurotoxic regimen of methamphetamine (MA). Administration of T at 24h prior to MA significantly increased striatal DA depletion in intact and gonadectomized male mice. Similar treatments administered to intact and gonadectomized female mice failed to alter striatal DA concentrations in response to MA. These results demonstrate that T can enhance MA-induced neurotoxicity in male, but not in female, mice. Such findings have important implications with regard to sex differences in nigrostriatal dopaminergic function, in general, and, in specific, to sex differences related to nigrostriatal dopaminergic neurotoxicity and neurodegeneration like that in response to MA and in Parkinson's disease, where a greater incidence is typically reported for males.
Department of Anatomy, Northeastern Ohio Universities College of Medicine (NEOUCOM), 4209 State Route 44, PO Box 95, Rootstown, OH 44272-0095, United States.
Chandani
C
Lewis
Dean E
DE
Dluzen
D000818:Animals; D002369:Castration / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D012727:Sex Characteristics; D043343:Testosterone Propionate / Q000494:pharmacology*
D018765:Dopamine Uptake Inhibitors; D008694:Methamphetamine; D004298:Dopamine; D043343:Testosterone Propionate