Methamphetamine-gonadal steroid hormonal interactions: effects upon acute toxicity and striatal dopamine concentrations.

Methamphetamine-gonadal steroid hormonal interactions: effects upon acute toxicity and striatal dopamine concentrations.

Dluzen Dean E; Anderson Linda I; Pilati Charles F

Neurotoxicology and teratology

2002

2002-04

Methamphetamine (MA)-related deaths and nigrostriatal dopaminergic (NSDA) neurotoxicity are greater in males. The exact basis for this gender difference is not known, but data, which show that estrogen (E) can function as a protectant of both the cardiovascular and NSDA systems, suggest an important role for gonadal steroids in modulating toxicity to this psychostimulant. In the present report, we examined the effects of treatment with the gonadal steroid hormones E and testosterone (T) upon MA-induced toxicity within intact and castrated female and male CD-1 mice. Treatment of intact males with E produced a severe acute toxicity to MA, with only 41% (7/17) males surviving at 24-h post-MA. This incidence of mortality was significantly different from that of nonhormonally treated mice receiving an identical regimen of MA [94% survival (16/17)]. None of the other treatment groups showed mortality rates, which differed significantly from the nonhormonally treated mice. Striatal dopamine (DA) concentrations of E-treated female mice (intact or castrated) were significantly greater than that of the nonhormonally treated mice, which failed to differ statistically among each other. In an attempt to understand some of the bases for the mortality rates in

Female; Male; Animals; Mice; Sex Factors; Body Weight/drug effects; Organ Size/drug effects; Dopamine/*metabolism; Body Temperature/drug effects; Methamphetamine/*toxicity; Corpus Striatum/*metabolism; Orchiectomy; Ovariectomy; Drug Interactions; Estrogens/pharmacology/*physiology; Heart Rate/drug effects; Heart Ventricles/metabolism; Norepinephrine/metabolism; Pituitary Gland/anatomy & histology; Testosterone/pharmacology/*physiology; Inbred Strains

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