Selective mu and delta, but not kappa, opiate receptor antagonists inhibitthe habituation of novelty-induced hypoalgesia in the rat

Rationale: There is now extensive evidence demonstrating that exposure to n ovel stimuli induces hypoalgesia and that this effect habituates over repea ted exposure to the stimuli. Moreover. it has been shown that administratio n of the nonselective opiate receptor antagonist naloxone can attenuate the rate of habituation of novelty-induced hypoalgesia. Objectives: The presen t experiments were conducted to determine the relative influence of differe nt opiate receptor subtypes in the attenuation of the habituation of novelt y-induced hypoalgesia. Methods: In experiments 1-3, different groups of mal e, Wistar rats (275-300 g) were administered vehicle, 0.5, 1.0 or 2.0-nmol doses of the mu-selective antagonist Cys(2)-Tyr(3)-Orn(5)-Pen(7)-amide (CTO P), the delta-receptor selective antagonist naltrindole, or the kappa-selec tive antagonist norbinaltorphimine (nor-BNI). In experiment 4, animals were administered vehicle, 5, 25 or 75-nmol doses of nor-BNI. All injections we re delivered to the right lateral ventricle 30 min prior to exposure to a n ever hot-plate apparatus (48.5 degrees C), once a day for eight consecutive days. Results: Paw-lick latencies in vehicle-treated animals were long dur ing the initial exposures and declined over repeated tests, suggesting the habituation of novelty-induced hypoalgesia. The rate of habituation was sig nificantly attenuated by administration of 1.0-nmol and 2.0-nmol doses of C TOP, by a 2.0-nmol dose of naltrindole, but was unaffected by all doses of nor-BNI. Conclusions: These results support the involvement of the Ct and d elta, but not the kappa, opiate receptor subtypes in the habituation of nov elty-induced hypoalgesia.