Effects of dopamine depletion on N-methyl-D-aspartate and dopamine receptor-mediated regulation of striatonigral neurons.

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Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Ganguly, Anindita.
Title Effects of dopamine depletion on N-methyl-D-aspartate and dopamine receptor-mediated regulation of striatonigral neurons.
Date 2000-05
Description The striatum receives dopamine (DA) and glutamate inputs which synapse on spiny efferent neurons. Glutamate acting via N-methyl-D-aspartate NMDA and non NMDA receptors regulates the firing of striatal efferent neurons, whereas D1 DA receptors modulate the responsiveness of these neurons to glutamate input. Studies indicate that DA depletion alters both NMDA and D1 DA receptor function in the striatum Thus, this thesis tested the overall hypothesis that DA-depleting brain lesions alter the interactions between NMDA receptors and D1 DA receptors, and thus the regulation of the striatonigral pathway when compared to neurologically intact animals. The overall hypothesis was tested by achieving the following specific aims. In specific aim 1, we examined the expression of the NR2A subunit of the NMDA receptor in striatonigral and striatopallidal neurons after unilateral DA depletion. Our results showed an increase in the NR2A subunit mRNA in both populations of striatal efferent neurons. As a consequence of DA depletion, therefore, the subunits from which NMDA receptors in striatal efferent neurons are composed are altered. In specific aim 2, we examined the effects of systemic NMDA receptor blockade by NM-801 on D1-agonist-induced immediate early gene (IEG) expression in the DA depleted striatum and provided evidence for decreased NMDA receptor involvement in D1-mediated gene regulation. In specific aim 3, we went on to further evaluate whether D1 DA receptor mediated EEG expression is differentially modulated by administration of distinct types of NMDA receptor antagonists in the DA-depleted striatum. Our results demonstrate that CGS 19755, which blocks both NR2A- and NR2B-containing NMDA receptors, suppressed D1-mediated <italic>c-fos
Type Text
Publisher University of Utah
Subject Physiology; Basal Ganglia
Subject MESH Neurons; Receptors, Dopamine
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Effects of dopamine depletion on N-methyl-D-aspartate and dopamine receptor-mediated regulation of striatonigral neurons." Spencer S. Eccles Health Sciences Library. Print version of "Effects of dopamine depletion on N-methyl-D-aspartate and dopamine receptor-mediated regulation of striatonigral neurons." available at J. Willard Marriott Library Special Collection. QP6.5 2000 .G35.
Rights Management © Anindita Ganguly.
Format Medium application/pdf
Identifier us-etd2,20
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s67s83ct
Setname ir_etd
ID 193390
Reference URL https://collections.lib.utah.edu/ark:/87278/s67s83ct