Relationships among gender, age, time, and temperature in methamphetamine-induced striatal dopaminergic neurotoxicity.
A neurotoxic regimen of methamphetamine (MA-40 mg/kg ip) administered at 0 (control-MA vehicle), 0.5 and 72 h prior to determinations of striatal dopamine (DA) and DOPAC (3,4-dihydroxyphenylacetic acid)/DA ratios were compared among juvenile and adult female and male mice. Adult females and males showed similar depletions in striatal DA at 0.5 h post-MA, but males showed greater DA depletions and DOPAC/DA ratios at 72 h post-MA. Juvenile mice showed neither sex differences, nor any MA neurotoxicity upon striatal DA or DOPAC/DA ratios. Following MA, body temperatures increased in all mice, but increases in adult males were greater than adult females; juveniles showed no sex differences and body temperature increases were similar to that of adult males. MA-evoked DA output was greater in adult compared to juvenile males and a biologically effective regimen of testosterone to juvenile males neither increased MA-evoked DA output nor decreased MA-induced striatal DA like that observed in adult males. These results demonstrate: (1) Unlike adults, juvenile mice show neither a sex difference for MA-induced neurotoxicity or body temperature increases, nor MA neurotoxicity, (2) Initial effects of MA (0.5 h) in adult females and males are similar, but at 72 h post-MA females show no further striatal DA depletion, (3) Increased striatal DA depletion within adult versus juvenile males may be related to initially higher MA-evoked DA responses, and (4) Testosterone fails to convert juvenile males into adults with regard to MA effects.
Dluzen
D E
DE
Department of Anatomy and Neurobiology, Northeastern Ohio Universities College of Medicine and Pharmacy, Rootstown, OH 44272-0095, USA. ded@neoucom.edu
McDermott
J L
JL
Darvesh
A S
AS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D012737:Sex Factors; D013997:Time Factors
D000697:Central Nervous System Stimulants; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D004298:Dopamine