Jan 18, 2011

Sex differences in methamphetamine toxicity in mice: effect on brain dopamine signaling pathways

M BourqueT Di Paolo


Male mice were reported to display greater methamphetamine-induced neurotoxicity than females. The present study evaluated the involvement of phosphatidylinositol-3 kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK1/2) pathways in this sex-dependent methamphetamine toxicity. Intact female and male mice were administered methamphetamine (20 or 40mg/kg) and euthanized a week later. Dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) autoradiography in the lateral striatum showed a greater sensitivity in male mice treated with 20mg/kg methamphetamine compared to female mice. Striatal dopamine concentration and DAT autoradiography showed a more extensive depletion in male mice given 40mg/kg methamphetamine compared to female mice. Mice administered 40mg/kg methamphetamine showed no sex difference in striatal VMAT2 autoradiography. In the substantia nigra, DAT specific binding was decreased only in male mice treated with 40mg/kg methamphetamine and DAT mRNA levels decreased in methamphetamine-treated female and male mice. Methamphetamine-treated male mice presented a dose-dependent decrease of VMAT2 mRNA levels. Methamphetamine reduced insulin-like growth factor 1 receptor levels in females at bot...Continue Reading

Mentioned in this Paper

MAPK1 wt Allele
Striatonigral Degeneration, Infantile (Disorder)
Homovanillic Acid
Biochemical Pathway
Cyclic AMP-Responsive DNA-Binding Protein
MAPK1 gene
Abnormal Degeneration
Tissue Membrane
MAPK3 wt Allele

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