Selective mu and delta, but not kappa, opiate receptor antagonists inhibit the habituation of novelty-induced hypoalgesia in the rat.
BACKGROUND
There is now extensive evidence demonstrating that exposure to novel stimuli induces hypoalgesia and that this effect habituates over repeated exposure to the stimuli. Moreover, it has been shown that administration of the nonselective opiate receptor antagonist naloxone can attenuate the rate of habituation of novelty-induced hypoalgesia.


OBJECTIVE
The present experiments were conducted to determine the relative influence of different opiate receptor subtypes in the attenuation of the habituation of novelty-induced hypoalgesia.


METHODS
In experiments 1-3, different groups of male, 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 (CTOP), the delta-receptor selective antagonist naltrindole, or the kappa-selective antagonist nor-binaltorphimine (nor-BNI). In experiment 4, animals were administered vehicle, 5, 25 or 75-nmol doses of nor-BNI. All injections were delivered to the right lateral ventricle 30 min prior to exposure to a novel hot-plate apparatus (48.5 degrees C), once a day for eight consecutive days.


RESULTS
Paw-lick latencies in vehicle-treated animals were long during the initial exposures and declined over repeated tests, suggesting the habituation of novelty-induced hypoalgesia. The rate of habituation was significantly attenuated by administration of 1.0-nmol and 2.0-nmol doses of CTOP, 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 mu and delta, but not the kappa, opiate receptor subtypes in the habituation of novelty-induced hypoalgesia.
Spreekmeester
E
E
Douglas Hospital Research Center, Department of Psychiatry, McGill University, Verdun, Quebec, Canada.
Rochford
J
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010146:Pain / Q000517:prevention & control / Q000523:psychology*; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; C055382:naltrindole