Estrogen and progesterone distinctively modulate methamphetamine-induced dopamine and serotonin depletions in C57BL/6J mice.
Intra-striatal infusion of a high dose (100 microg/3 microl) of methamphetamine produced long-lasting depletions of striatal dopamine and serotonin in both male and female mice. Male mice exhibited a greater depletion of striatal dopamine and serotonin than female mice. A similar trend of sexual differences was observed when 4 cumulative doses of methamphetamine were administered systemically. Thus, the sexual differences in methamphetamine-induced neurotoxicity in the striatum are probably not due to their differences in peripheral metabolism of methamphetamine. Moreover, ovariectomized (OVX) mice supplemented with 3 daily doses of estradiol benzoate (EB) at high or physiological levels, 3 daily doses of progesterone (P), and 2 doses of EB followed by 1 dose of P all demonstrated higher striatal dopamine levels following methamphetamine treatment as compared to vehicle-supplemented controls. The OVX mice pretreated with 3 daily doses of P exhibited the highest striatal serotonin levels after methamphetamine administration of all groups. In conclusion, sexual differences observed in methamphetamine-induced striatal neurotoxicity may be modulated by ovarian hormones.
Yu
L
L
Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan. lungyu@mail.ncku.edu.tw
Liao
P C
PC
D000818:Animals; D004298:Dopamine / Q000172:deficiency*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D010053:Ovary / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D012701:Serotonin / Q000172:deficiency*; D012737:Sex Factors
D004967:Estrogens; D009498:Neurotoxins; D012701:Serotonin; D008694:Methamphetamine; D011374:Progesterone; D004298:Dopamine