Naloxone potentiation of novelty-induced hypoalgesia: characterization of the alpha-noradrenergic receptor subtype.

Repeated daily administration of the opiate receptor antagonist naloxone (10 mg/kg) attenuates the habituation of novelty-induced hypoalgesia. This effect can be reversed by the alpha 2-noradrenergic receptor agonist clonidine and enhanced by the alpha 2-antagonist yohimbine. The present experiments were conducted to provide further support for the importance of the alpha 2-receptor and determine the possible influence of the alpha 1-receptor. Naloxone's effect on novelty-induced hypoalgesia was not affected by pretreatment with the specific alpha 1-receptor antagonist prazosin (0.2-1.0 mg/kg, SC) or the nonselective alpha antagonist phentolamine (2.0-10.0 mg/kg). In a second series of experiments, it was found that the potentiation of naloxone's effect by yohimbine (2 mg/kg) was reversed by clonidine (0.1 mg/kg) but was not influenced by prazosin or phentolamine. These results suggest that the alpha 1-noradrenergic receptor subtype does not mediate the effect of naloxone on novelty-induced hypoalgesia. They also reinforce the importance of the alpha 2-receptor subtype in the mediation of this effect.