Sex and temporally-dependent effects of methamphetamine toxicity on dopamine markers and signaling pathways

Title

Sex and temporally-dependent effects of methamphetamine toxicity on dopamine markers and signaling pathways

Creator

Bourque M; Dluzen D E; Di Paolo T

Publisher

Neuropharmacology

Date

2012
2012-06

Description

Methamphetamine induces a greater neurodegenerative effect in male versus female mice. In order to investigate this sex difference we studied the involvement of Akt and extracellular signal-regulated kinase (ERK1/2) in methamphetamine toxicity as a function of time post-treatment (30 min, 1 and 3 days). Methamphetamine-induced decreases in dopamine concentrations and dopamine transporter (DAT) specific binding in the medial striatum were similar in female and male mice when evaluated 1 day post-methamphetamine (40 mg/kg). At 3 days post-methamphetamine, striatal dopamine concentration and DAT specific binding continued to decline in males, whereas females showed a recovery with increases in dopamine content and DAT specific binding in medial striatum at day 3 versus day 1 post-methamphetamine. The reduction in striatal vesicular monoamine transporter 2 specific binding observed at 1 and 3 days post-methamphetamine showed neither a sex- nor temporal-dependant effect. Under the present experimental conditions, methamphetamine treatments had modest effects on dopamine markers measured in the substantia nigra. Proteins assessed by Western blots showed similar reductions in both female and male mice for DAT proteins at 1 and 3 days post-methamphetamine. An increase in the phosphorylation of striatal Akt (after 1 day), glycogen synthase kinase 3 beta (at 1 and 3 days) and ERK1/2 (30 min post-methamphetamine) was only observed in females. Striatal glial fibrillary acidic protein levels were augmented in both females and males at 3 days post-methamphetamine. These results reveal some of the sex- and temporally-dependent effects of methamphetamine toxicity on dopaminergic markers and suggest some of the signaling pathways associated with these responses. (C) 2012 Elsevier Ltd. All rights reserved.

Subject

dopamine; Akt; Neurosciences & Neurology; Pharmacology & Pharmacy; gene-expression; estrous-cycle; striatum; protein-phosphorylation; markers; glycogen-synthase kinase-3-beta; Methamphetamine; Sex difference; evoked striatal dopamine; induced neurotoxicity; monoamine; neuronal apoptosis; neurotoxicity; physiological functions; terminal; transporters

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

2363-2372

Issue

7

Volume

62

Citation

Bourque M; Dluzen D E; Di Paolo T, “Sex and temporally-dependent effects of methamphetamine toxicity on dopamine markers and signaling pathways,” NEOMED Bibliography Database, accessed March 5, 2021, https://neomed.omeka.net/items/show/8695.

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