Mu and delta opioid receptor gene expression after chronic treatment with opioid agonist

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 opioid receptors were found in the caudate-putamen, nucleus accumbens, thalamus and periaquaductal gray. After continuous morphine treatment for 7 days both mu and delta opioid receptor mRNA levels were unchanged in 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 delta receptors, did not reduce receptor number at either time point. The reduction in delta receptor binding after DSLET treatment was not accompanied by significantly diminished levels of delta receptor mRNA. Unaltered mu and delta receptor mRNA levels in brain after chronic morphine exposure make it unlikely that adaptive changes in the transcription of these genes play a role in the observed tolerance in opioid regulation of adenylyl cyclase.