Lack of effect of naloxone on autoanalgesia

Autoanalgesia (behaviorally-induced antinociception) may be elicited by acute stress or clasically conditioned fear. Antinociception within both of these paradigms is reportedly associated with increased CNS opioid peptide activity. Large doses of naloxone (20 mg/kg) failed to modify antinociception elicited by acute footshock or conditioned fear in rats. Naloxone (4 mg/kg) was also ineffective against antinociception following footshock in mice. These data suggest that if an endorphin does mediate autoanalgesia, the affinity of its receptor for naloxone is very low. Alternatively, parallel opioid and non-opioid systems may be activated by autoanalgesic procedures, with antagonism of the opioid component being insufficient to reduce the antinociception.