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

Title

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

Creator

Bourque M; Liu B; Dluzen D E; Di Paolo T

Publisher

Psychoneuroendocrinology

Date

2011
2011-08

Description

Mate 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 40 mg/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 20 mg/kg methamphetamine compared to female mice. Striatal dopamine concentration and DAT autoradiography showed a more extensive depletion in male mice given 40 mg/kg methamphetamine compared to female mice. Mice administered 40 mg/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 40 mg/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 both methamphetamine doses tested whereas it elevated G protein-coupled estrogen receptor 1 (GPER1) only in male mice. Phosphorylated Akt levels decreased only in male mice treated with 40 mg/kg methamphetamine. Glycogen synthase kinase 30 levels were reduced in male mice at both methamphetamine doses tested and in females receiving 40 mg/kg. Bcl-2 Levels were increased in male mice treated with methamphetamine, whereas ERK1/2 and BAD levels were unchanged. These results implicate some of the signaling pathways associated with the sex differences in methamphetamine-induced toxicity. (C) 2011 Elsevier Ltd. All rights reserved.

Subject

dopamine; mice; Psychiatry; Akt; 3; 2; 1-methyl-4-phenyl-1; Neurosciences & Neurology; Endocrinology & Metabolism; cell-death; activation; neurotoxicity; induced; rat striatum; kinase; striatum; Methamphetamine; evoked striatal dopamine; neurotoxicity; cd-1; element-binding protein; Sex difference; transporter function; 6-tetrahydropyridine mice

Format

Journal Article or Conference Abstract Publication

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

955-969

Issue

7

Volume

36

Citation

Bourque M; Liu B; Dluzen D E; Di Paolo T, “Sex differences in methamphetamine toxicity in mice: Effect on brain dopamine signaling pathways,” NEOMED Bibliography Database, accessed September 23, 2021, https://neomed.omeka.net/items/show/8697.

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