Glutamate, characterization of its role in methamphetamine neurotoxicity and its interaction with dopamine in the rat striatum

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Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Elayan, Ikram Mohammad
Title Glutamate, characterization of its role in methamphetamine neurotoxicity and its interaction with dopamine in the rat striatum
Date 1994-12
Description Systemic administration of methamphetamine (Meth) causes neurochemical deficits in terminals of the nigrostriatal dopaminergic system. The mechanism by which Meth causes this neurotoxicity is still not known. Several investigators have suggested that the excitatory neurotransmitter, glutamate (Glu), participates in mediating this neurotoxicity. The current study was conducted to investigate the role of Meth on Glu release by utilizing both in vitro and in vivo systems. Incubation of glutamatergic neurons with Meth in vitro failed to release Glu from these neurons. Also, perfusing striatal slices with Meth, in vitro, failed to release Glu from these slices. These results suggested that a complete neuronal circuit might be needed in order for Meth to affect Glu release in the striatum. Therefore, in vivo microdialysis techniques were utilized to investigate the release of Glu in the striatum. No difference was observed in Glu levels in perfusates of animals treated with a single dose of Meth, administered ten minutes after a single dose of iprindole, in comparison to control animals. When DL-threo-$/beta$-hydroxyaspartic acid, a Glu uptake blocker, was given with Meth, Glu concentrations in striatal dialysate of rats treated with Meth + blocker were significantly higher than those in the blocker alone-treated group. These higher levels of striatal Glu in response to Meth treatment may contribute to Meth neurotoxicity since Glu causes neurotoxicity. Perfusion of the Glu uptake blocker alone into the striatum increased Glu levels in the extracellular space. These levels of Glu were maintained only for 1 h and then declined to almost 50% of the peak value even though the blocker was continuously administered through the dialysis probe. Haloperidol, a dopamine D2 receptor antagonist, and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline (NBQX), a non-N-methyl-D-aspartic acid (NMDA) Glu receptor antagonist, partially inhibited this decline in Glu levels. These results may be due to an inhibitory effect of dopamine on Glu release in the striatum through a D2 receptor. The finding that NBQX partially blocked this decline in Glu levels raises the possibility of an inhibitory non-NMDA autoreceptor on the corticostriatal pathway. The Glu uptake blocker alone also increased extracellular DA levels in the striatum, which is the first report of this phenomenon.
Type Text
Publisher University of Utah
Subject Neurotoxicity; Cerebellar Granule Cells
Subject MESH Methamphetamine; Pharmacology; Glutamic Acid; Dopamine
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Glutamate, characterization of its role in methamphetamine neurotoxicity and its interaction with dopamine in the rat striatum." Spencer S. Eccles Health Sciences Library. Print version of "Glutamate, characterization of its role in methamphetamine neurotoxicity and its interaction with dopamine in the rat striatum." available at J. Willard Marriott Library Special Collection. RM31.5 1994 .E43.
Rights Management © Ikram Mohammad Elayan.
Format Medium application/pdf
Format Extent 1,205,457 bytes
Identifier undthes,4805
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship National Institute on Drug Abuse and by a fellowship from the University of Utah.
Master File Extent 1,205,512 bytes
ARK ark:/87278/s6416zzh
Setname ir_etd
Date Created 2012-04-24
Date Modified 2012-04-24
ID 191767
Reference URL https://collections.lib.utah.edu/ark:/87278/s6416zzh