Document Detail


Striatal CB1 and D2 receptors regulate expression of each other, CRIP1A and δ opioid systems.
MedLine Citation:
PMID:  23286559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although biochemical and physiological evidence suggests a strong interaction between striatal CB1 cannabinoid (CB1 R) and D2 dopamine (D2 R) receptors, the mechanisms are poorly understood. We targeted medium spiny neurons of the indirect pathway using shRNA to knockdown either CB1 R or D2 R. Chronic reduction in either receptor resulted in deficits in gene and protein expression for the alternative receptor and concomitantly increased expression of the cannabinoid receptor interacting protein 1a (CRIP1a), suggesting a novel role for CRIP1a in dopaminergic systems. Both CB1 R and D2 R knockdown reduced striatal dopaminergic-stimulated [(35) S]GTPγS binding, and D2 R knockdown reduced pallidal WIN55212-2-stimulated [(35) S]GTPγS binding. Decreased D2 R and CB1 R activity was associated with decreased striatal phosphoERK. A decrease in mRNA for opioid peptide precursors pDYN and pENK accompanied knockdown of CB1 Rs or D2 Rs, and over-expression of CRIP1a. Down-regulation in opioid peptide mRNAs was followed in time by increased DOR1 but not MOR1 expression, leading to increased [D-Pen2, D-Pen5]-enkephalin-stimulated [(35) S]GTPγS binding in the striatum. We conclude that mechanisms intrinsic to striatal medium spiny neurons or extrinsic via the indirect pathway adjust for changes in CB1 R or D2 R levels by modifying the expression and signaling capabilities of the alternative receptor as well as CRIP1a and the DELTA opioid system.
Authors:
Lawrence C Blume; Caroline E Bass; Steven R Childers; George D Dalton; David C S Roberts; Jasmine M Richardson; Ruoyu Xiao; Dana E Selley; Allyn C Howlett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2013-01-31
Journal Detail:
Title:  Journal of neurochemistry     Volume:  124     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-04     Completed Date:  2013-04-29     Revised Date:  2014-05-05    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  808-20     Citation Subset:  IM    
Copyright Information:
© 2013 International Society for Neurochemistry.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carrier Proteins / biosynthesis*,  genetics,  physiology
Corpus Striatum / metabolism*
Gene Expression Regulation
Gene Knockdown Techniques / methods
Male
Mice
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 / antagonists & inhibitors,  physiology*
Receptors, Dopamine D2 / antagonists & inhibitors,  physiology*
Receptors, Opioid, delta / biosynthesis*,  genetics
Grant Support
ID/Acronym/Agency:
F31 DA032215/DA/NIDA NIH HHS; F31-DA032215/DA/NIDA NIH HHS; F32-DA026295/DA/NIDA NIH HHS; K01 DA024763/DA/NIDA NIH HHS; K01-DA024763/DA/NIDA NIH HHS; P50 DA006634/DA/NIDA NIH HHS; P50-DA006634/DA/NIDA NIH HHS; R01 DA003690/DA/NIDA NIH HHS; R01 DA014030/DA/NIDA NIH HHS; R01 DA014030/DA/NIDA NIH HHS; R01 DA030161/DA/NIDA NIH HHS; R01-DA03690/DA/NIDA NIH HHS; R21-DA025321/DA/NIDA NIH HHS; T32-DA00724/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Cnrip1 protein, rat; 0/Receptor, Cannabinoid, CB1; 0/Receptors, Dopamine D2; 0/Receptors, Opioid, delta
Comments/Corrections

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