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Schizophrenia Research and Treatment
Volume 2011, Article ID 542896, 11 pages
http://dx.doi.org/10.1155/2011/542896
Research Article

Abnormal Behaviors and Microstructural Changes in White Matter of Juvenile Mice Repeatedly Exposed to Amphetamine

1Department of Anatomy, School of Medicine, Southern Illinois University Carbondale, 1135 Lincoln Drive, Carbondale, IL 62901, USA
2Department of Computer Science, Southern Illinois University Carbondale, IL 62901-4328, USA

Received 1 February 2011; Revised 24 March 2011; Accepted 2 May 2011

Academic Editor: George Bartzokis

Copyright © 2011 Hong-Ju Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Amphetamine (AMP) is an addictive CNS stimulant and has been commonly abused by adolescents and young adults, during which period brain white matter is still developing. This study was to examine the effect of a nonneurotoxic AMP on the white matter of juvenile mice. d-AMP (1.0 mg/kg) was given to young male C57BL/6 mice once a day for 21 days. The spatial working memory and locomotion of mice were measured at the end. Then, mice were sacrificed and their brains were processed for morphological analyses to examine the white matter structure and for Western blot analysis to measure three main proteins expressed in mature oligodendrocytes. AMP-treated mice displayed higher locomotion and spatial working memory impairment and showed lower levels of Nogo-A and GST-pi proteins in frontal cortex and lower MBP protein in the frontal cortex and hippocampus. They also had fewer mature oligodendrocytes and weak MBP immunofluorescent staining in the same two brain regions. But the striatum was spared. These results suggest that the late-developing white matter is vulnerable to AMP treatment which is able to increase striatal and cortical dopamine. Both the compromised white matter and increased dopamine may contribute to the observed behavioral changes in AMP-treated mice.