ETONITAZENE-INDUCED ANTINOCICEPTION IN MU(1) OPIOID RECEPTOR-DEFICIENT CXBK MICE - EVIDENCE FOR A ROLE FOR MU(2) RECEPTORS IN SUPRASPINAL ANTINOCICEPTION

The prevailing view is that supraspinal mu opioid-mediated antinociception in mice is mediated via the mu(1) L subtype. The purpose of the present study was to determine if the highly mu-selective compound etonitazene could produce supraspinal (intracerebroventricular; i.c.v.) antinociception in CXBK mice, which are deficient in brain mu(1), but not mu(2), opioid receptors. CXBK or normal Crl:CD-1(R)(ICR)BR mice were administered graded doses of etonitazene i.c.v. and 15 min later antinociception was assessed by a standard radiant-heat or 55 degrees C water tail-flick test. Etonitazene produced dose-related antinociception that was blocked by naloxone and by beta-FNA (demonstrating a mu opioid mechanism), but not by either ICI-174,864 or naltrindole (demonstrating the lack of involvement of delta opioid receptors). These findings suggest that mu(2) opioid receptors are important contributors to opioid-induced supraspinal antinociception in mice.