Components of the opioid withdrawal syndrome in mice are thermoregulatory responses.

C57BL/6J mice were rendered physically dependent on morphine by giving them ad lib access to a drinking fluid containing 0.2% saccharin and morphine for 14 days at 20-22 degrees C. Core body temperatures were monitored by radio telemetry, which obviated the need for restraint, handling, or otherwise disturbing the animals. Consistent hyperthermia was present throughout the morphine intoxication phase, followed by hypothermia after the withdrawal syndrome had been precipitated by naloxone challenge (2.0 mg/kg, IP) at 22.5 degrees C. The hypothermia could be blocked by exposing the animals to a 34.5 degrees C ambient temperature, which also prevented the occurrence of tremor and "wet dog shakes." In contrast, the other withdrawal signs monitored were not significantly affected. In a second experiment, mice were given the same morphine-saccharin drinking fluid as before, except that a choice was provided between two interconnected home cages (23 degrees C vs. 35 degrees C) throughout the experiment. A marked preference for the 35 degrees C cage was seen during intoxication, which served to enhance the hyperthermia due to morphine. Following withdrawal, when hypothermia is evident, the preference for the 35 degrees C cage declined to control levels. These results suggest that hypothermia is both a consequence and a contributor to the opioid withdrawal syndrome.