Effect of naloxone on the habituation of novelty-induced hypoalgesia: the collateral inhibition hypothesis revisited.

Repeated daily administration of the opiate receptor antagonist naloxone prior to hotplate tests provokes longer paw-lick latencies by attenuating the habituation of novelty-induced hypoalgesia. This hypoalgesia has been found to persist when pain tests are subsequently conducted following saline administration. The present experiments were conducted to determine whether the substrates mediating the hypoalgesia observed during naloxone and saline tests are similar or distinct. Neither the hypoalgesia observed during naloxone nor saline tests were affected by the induction of tolerance to the hypoalgesic effect of morphine, suggesting that both effects are mediated by nonopioid antinociceptive mechanisms. Previous work from our laboratory demonstrated that the hypoalgesia observed during naloxone tests is inhibited by clonidine, enhanced by yohimbine, and unaffected by prazosin and phentolamine. In the present article, we report a similar pattern of results for the hypoalgesia observed during saline tests. It is concluded that the substrates mediating both effects are similar. The results are discussed in relation to the possibility that an opioid substrate involved in habituative learning may be inhibitory on a nonopioid antinociceptive substrate.