Effect of cold acclimation and repeated swimming on opioid and nonopioid swim stress-induced analgesia in selectively bred mice

Abstract

Swiss–Webster mice selectively bred for high swim stress-induced analgesia (SSIA) were exposed to continuous ambient cold (5 °C) for 6 weeks or to daily 3-min swims for 14 consecutive days either in 20 or 32 °C water. Thereafter, mice subjected to the particular procedure were injected intraperitoneally with 10 mg/kg of naltrexone HCl and were tested for modification of the opioid and nonopioid component of SSIA. SSIA was reduced following swims at either water temperature and was antagonized by naltrexone to greater extent than in nonswimming mice. Thus, the nonopioid (i.e. naltrexone-resistant) portion of the overall SSIA was significantly reduced, whereas the opioid (naltrexone-sensitive) portion became relatively augmented. In contrast, SSIA differed neither in magnitude nor in sensitivity to naltrexone between cold-acclimated and unacclimated mice. Swim hypothermia as well as the nonopioid component of SSIA were decreased after repeated swimming at 32 and 20 °C, but remained unchanged after cold acclimation. This argues for the essential role of an extrathermal, probably emotional in nature, factor not only in the elicitation of nonopioid SSIA, but also in the modulation of thermoregulatory processes during swimming. We suggest that the emergency component of swim stress, together with initial moderate hypothermic challenge, first produces the opioid form of SSIA, and subsequently, as the swim continues, also affects the thermoregulatory processes maintaining thermal homeostasis. This causes further increase in swim hypothermia and raises its stressing property to induce the nonopioid form of SSIA.