Endogenous opioid system down-regulation during hibernation in amphibians

In late summer, Northern grass frogs, Rana pipiens, intraspinally administered dynorphin produces a potent, dose-dependent antinociceptive action as measured by the acetic acid test used to evoke a hindlimb wiping response. Surprisingly, in fall, frogs which have entered hibernation, intraspinal dynorphin produces no antinociception action. Intraspinal morphine shows a decreased effect in fall frogs while systemic morphine is equi-effective in summer and fall frogs. Immobilization stress, previously shown to be mediated by endogenous opioid systems in this amphibian, produces a robust increase in nociceptive thresholds in summer frogs while the nociceptive thresholds of fall frogs are unaffected by this procedure. Summer frogs adapted to cold room (4 degrees C) show a significant decrease in nociceptive thresholds compared to cohorts kept at room temperature, and cold-adapted frogs returned to room temperature show a naloxone-attenuated increase in nociceptive threshold. Collectively, these data suggest that endogenous opioid systems in these northern frogs are down-regulated during fall hibernation.