Effects of time of testing, stress level, and number of conditioning days on naloxone sensitivity of conditioned stress-induced analgesia in rats.

Controversy exists as to whether conditioned stress-induced analgesia (CSIA) utilizes opioid or nonopioid mechanisms. In two experiments, both an anticipatory conditioned stimulus (CS) and a shock-associated CS were used. The duration of exposure to the anticipatory CS was long, as in studies reporting opioid CSIA, whereas the duration of the shock-associated CS was short, as in studies reporting nonopioid CSIA. In addition, the effects of unconditioned stimulus (UCS) strength were investigated by using three levels of footshock (no, moderate, and high), and the development of CSIA was monitored by using different levels of training (1 to 6 days). CSIA, measured in both anticipatory and postexposure test periods, was found to be relatively stable across tail-flick trials within days and insensitive to strength of shock. As training progressed, CSIA increased with repeated CS-UCS pairings. We tested for opioid involvement using naloxone and found opioid and nonopioid mechanisms underlying CSIA; these mechanisms combined to form a stable level of analgesia. Our data suggest that stress level and amount of training interact to activate opioid and nonopioid mechanisms of CSIA. Apparent discrepancies in previous studies regarding naloxone sensitivity of CSIA may therefore be attributable to differences in stress levels, test periods and durations of exposure to shock-related cues.