Opioid receptor upregulation in mu-opioid receptor deficient CXBK and outbred Swiss Webster mice

Chronic in vivo treatment with opioid antagonists increases opioid receptor density and the potency of opioid agonists without altering receptor mRNA levels. To determine if basal receptor density affects opioid receptor upre gulation, we examined the effect of chronic naltrexone treatment on CI-opio id receptor density and mRNA in two mice strains that differ in CL-opioid r eceptor density. CXBK mice (CL-opioid receptor deficient) and outbred Swiss Webster mice were implanted s.c. with a placebo or 15 mg naltrexone pellet for 8 days, the pellets removed and 24 hr later opioid receptor density (m u, delta) and receptor mRNA level (mu) determined in whole brain; or morphi ne dose-response studies conducted. In placebo-treated CXBK mice, FL-opioid receptor density was approximate to 40% less than in Swiss Webster mice, a lthough mu-opioid receptor mRNA abundance was similar in both strains. In p lacebo-treated CXBK mice, morphine potency was approximate to 6-fold less t han Swiss Webster mice. Naltrexone treatment increased morphine potency (1. 7-fold) and mu-(approximate to 90%) and delta- (approximate to 20-40%) opio id receptor density in CXBK and Swiss Webster mouse brain similarly. mu-opi oid receptor mRNA was unchanged by naltrexone treatment in either strain. T here was no difference in the basal or naltrexone-treated whole brain Gi, p rotein levels in CXBK or Swiss Webster mouse. These data indicate that a de ficiency in mu-opioid receptors does not alter the regulation of opioid rec eptors by opioid antagonists in vivo, and suggest that adaptive responses t o chronic opioid antagonist treatment are independent of opioid receptor de nsity.