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The Journal of Neuroscience, June 20, 2007, 27(25):6823-6831; doi:10.1523/JNEUROSCI.0013-07.2007

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Neurobiology of Disease
Dynamic Changes in Vesicular Glutamate Transporter 1 Function and Expression Related to Methamphetamine-Induced Glutamate Release

Karla A. Mark,1 Maria S. Quinton,1 Shelley J. Russek,2 and Bryan K. Yamamoto1

Laboratories of 1Neurochemistry and 2Molecular Neurobiology, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts 02118

Correspondence should be addressed to Bryan K. Yamamoto, Department of Pharmacology, Boston University School of Medicine, 715 Albany Street, L-613, Boston, MA 02118. Email: bkyam{at}bu.edu

The vesicular glutamate (GLU) transporter (VGLUT1) is a critical component of glutamatergic neurons that regulates GLU release. Despite the likely role of GLU release in drug abuse pathology, there is no information that links VGLUT1 with drugs of abuse. This study provides the first evidence that methamphetamine (METH) alters the dynamic regulation of striatal VGLUT1 function and expression through a polysynaptic pathway. METH increases cortical VGLUT1 mRNA, striatal VGLUT1 protein in subcellular fractions, and the Vmax of striatal vesicular GLU uptake. METH also increases glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein in the crude vesicle fraction. METH-induced increases in cortical VGLUT1 mRNA, as well as striatal VGLUT1 and GAPDH, are GABAA receptor-dependent because they are blocked by GABAA receptor antagonism in the substantia nigra. These results show that VGLUT1 can be dynamically regulated via a polysynaptic pathway to facilitate vesicular accumulation of GLU for subsequent release after METH.

Key words: methamphetamine; VGLUT1; basal ganglia; striatum; substantia nigra; glutamate


Received Jan. 3, 2007; revised April 18, 2007; accepted May 11, 2007.

Correspondence should be addressed to Bryan K. Yamamoto, Department of Pharmacology, Boston University School of Medicine, 715 Albany Street, L-613, Boston, MA 02118. Email: bkyam{at}bu.edu






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