Opioid μ receptor subtypes (possibly μ1 and μ2) revealed by morphine-induced antinociception vs endothelin-1 in recombinant inbred CXBK mice

Abstract Morphine was administered intracerebroventricularly to normal or recombinant inbred CXBK (μ-opioid receptor deficient) mice and antinociception was determined against two different stimuli. Morphine-induced antinociception agains acetylcholine was strain-dependent, whereas against endothelin-1 it was not. The antinociception was mediated via opioid μ receptors (blocked by β-FNA, but not naltrindole, ICI 174,864 or nor -BNI) through separate pathways, one naloxonazine-sensitive and the other naloxonazine-insensitive. Taken together, these results appear to demonstrate supraspinal morphine-induced antinociception through distinct subtypes of the μ opioid receptor, supporting the possibility of novel subtype-selective therepeutic agents with greater separation between analgesia and side-effects or physical dependence. Furthermore, the methodology described herein provides model systems for the in vivo screening of such agents.