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Striatal CB 1 and D 2 receptors regulate expression of each other, CRIP 1A and delta opioid systems
Author(s) -
Blume Lawrence C.,
Bass Caroline E.,
Childers Steven R.,
Dalton George D.,
Roberts David C. S.,
Richardson Jasmine M.,
Xiao Ruoyu,
Selley Dana E.,
Howlett Allyn C.
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12139
Subject(s) - gene knockdown , dopaminergic , receptor , enkephalin , striatum , medium spiny neuron , chemistry , g protein , cannabinoid receptor , microbiology and biotechnology , cannabinoid , opioid , biology , medicine , dopamine , endocrinology , biochemistry , gene , agonist
Abstract Although biochemical and physiological evidence suggests a strong interaction between striatal CB 1 cannabinoid (CB 1 R) and D 2 dopamine (D 2 R) receptors, the mechanisms are poorly understood. We targeted medium spiny neurons of the indirect pathway using shRNA to knockdown either CB 1 R or D 2 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 CB 1 R and D 2 R knockdown reduced striatal dopaminergic‐stimulated [ 35 S]GTPγS binding, and D 2 R knockdown reduced pallidal WIN55212‐2‐stimulated [ 35 S]GTPγS binding. Decreased D 2 R and CB 1 R activity was associated with decreased striatal phosphoERK. A decrease in mRNA for opioid peptide precursors pDYN and pENK accompanied knockdown of CB 1 Rs or D 2 Rs, and over‐expression of CRIP1a. Down‐regulation in opioid peptide mRNA s 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 CB 1 R or D 2 R levels by modifying the expression and signaling capabilities of the alternative receptor as well as CRIP1a and the DELTA opioid system.