Naloxone-induced analgesia and morphine supersensitivity effects are contingent upon prior exposure to analgesic testing.

Repeated administrations of naloxone have been found to result in the development of analgesia. Pretreatment with naloxone can also produce supersensitivity to morphine. This study examined whether the development of these phenomena is affected by exposure to pain (hot-plate testing) during opiate blockade. During acquisition, two experimental groups of rats received identical treatment with respect to repeated naloxone injections (5 mg/kg) and the environment in which the injections were administered. A "contingent" group (NAL-C) received hot-plate testing under the influence of naloxone, while a "noncontingent" group (NAL-NC) experienced hot-plate testing and naloxone separated by an interval of 24 h. At test, NAL-C rats manifested naloxone-induced analgesia (NIA) whereas the NAL-NC animals did not. The NAL-C rats also showed supersensitivity to the analgesic effects of morphine (3 mg/kg) and to the cataleptic effects of morphine (17.5 mg/kg) while the NAL-NC rats did not differ from saline controls. Thus, both NIA and morphine supersensitivity were completely dependent on testing in the drug state during acquisition; mere exposure to an identical regime of naloxone injections was insufficient to produce these phenomena.