Document Detail


Deletion of the NMDA-NR1 receptor subunit gene in the mouse nucleus accumbens attenuates apomorphine-induced dopamine D1 receptor trafficking and acoustic startle behavior.
MedLine Citation:
PMID:  23345061     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The nucleus accumbens (Acb) contains subpopulations of neurons defined by their receptor content and potential involvement in sensorimotor gating and other behaviors that are dysfunctional in schizophrenia. In Acb neurons, the NMDA NR1 (NR1) subunit is coexpressed not only with the dopamine D1 receptor (D1R), but also with the µ-opioid receptor (µ-OR), which mediates certain behaviors that are adversely impacted by schizophrenia. The NMDA-NR1 subunit has been suggested to play a role in the D1R trafficking and behavioral dysfunctions resulting from systemic administration of apomorphine, a D1R and dopamine D2 receptor agonist that impacts prepulse inhibition to auditory-evoked startle (AS). Together, this evidence suggests that the NMDA receptor may regulate D1R trafficking in Acb neurons, including those expressing µ-OR, in animals exposed to auditory startle and apomorphine. We tested this hypothesis by combining spatial-temporal gene deletion technology, dual labeling immunocytochemistry, and behavioral analysis. Deleting NR1 in Acb neurons prevented the increase in the dendritic density of plasma membrane D1Rs in single D1R and dual (D1R and µ-OR) labeled dendrites in the Acb in response to apomorphine and AS. Deleting NR1 also attenuated the decrease in AS induced by apomorphine. In the absence of apomorphine and startle, deletion of Acb NR1 diminished social interaction, without affecting novel object recognition, or open field activity. These results suggest that NR1 expression in the Acb is essential for apomorphine-induced D1R surface trafficking, as well as auditory startle and social behaviors that are impaired in multiple psychiatric disorders.
Authors:
Michael J Glass; Danielle C Robinson; Elizabeth Waters; Virginia M Pickel
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-03-05
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  67     ISSN:  1098-2396     ISO Abbreviation:  Synapse     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-18     Completed Date:  2013-10-29     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  United States    
Other Details:
Languages:  eng     Pagination:  265-79     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apomorphine / pharmacology*
Carrier Proteins / genetics,  metabolism*
Cell Membrane / metabolism
Dendrites / metabolism
Gene Deletion
Mice
Mice, Transgenic
Nerve Tissue Proteins / genetics,  metabolism*
Nucleus Accumbens / cytology,  metabolism*,  physiology
Pattern Recognition, Physiological
Protein Transport / genetics
Receptors, Dopamine D1 / metabolism*
Receptors, N-Methyl-D-Aspartate / genetics,  metabolism*
Receptors, Opioid, mu / metabolism
Sensory Gating / genetics*
Social Behavior
Grant Support
ID/Acronym/Agency:
DA024030/DA/NIDA NIH HHS; DA027128/DA/NIDA NIH HHS; DA04600/DA/NIDA NIH HHS; MH40342/MH/NIMH NIH HHS; R01 DA004600/DA/NIDA NIH HHS; R01 DA024030/DA/NIDA NIH HHS; R01 MH040342/MH/NIMH NIH HHS; R03 DA027128/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Gprin1 protein, mouse; 0/NR1 NMDA receptor; 0/Nerve Tissue Proteins; 0/Receptors, Dopamine D1; 0/Receptors, N-Methyl-D-Aspartate; 0/Receptors, Opioid, mu; N21FAR7B4S/Apomorphine
Comments/Corrections

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