Estrogen and progesterone distinctively modulate methamphetamine-induced dopamine and serotonin depletions in C57BL/6J mice

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Intra-striatal infusion of a high dose (100 μg/3 μl) 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.

Original languageEnglish
Pages (from-to)1139-1147
Number of pages9
JournalJournal of Neural Transmission
Issue number10
Publication statusPublished - 2000 Nov 20


All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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