B. Buzas et al., MU-OPIOID AND DELTA-OPIOID RECEPTOR GENE-EXPRESSION AFTER CHRONIC TREATMENT WITH OPIOID AGONIST, NeuroReport, 7(9), 1996, pp. 1505-1508
LEVELS Of mRNA coding for mu and delta opioid receptors were evaluated
by competitive PCR in regions of rat brain where adaptive changes in
opioid regulation of adenylyl cyclase occur following chronic morphine
treatment. Correlation between receptor protein and mRNA levels after
exposure to full and partial agonists were also investigated in NG108
-15 cells. Different basal gene expression levels of mu and delta opio
id receptors were found in the caudate-putamen, nucleus accumbens, tha
lamus and periaquaductal gray. After continuous morphine treatment for
7 days both mu and delta opioid receptor mRNA levels were unchanged i
n all four regions compared with saline-treated controls. In NG108-15
cells marked down-regulation of delta opioid receptors as measured by
radioligand binding was observed after 5 or 24 h full agonist (D-Ser(2
)-Leu-enkephalin; DSLET) treatment. Morphine, a partial agonist at del
ta receptors, did not reduce receptor number at either time point. The
reduction in delta receptor binding after DSLET treatment was not acc
ompanied by significantly diminished levels of delta receptor mRNA. Un
altered mu and delta receptor mRNA levels in brain after chronic morph
ine exposure make it unlikely that adaptive changes in the transcripti
on of these genes play a role in the observed tolerance in opioid regu
lation of adenylyl cyclase.