Barbiturate physical dependence in mice: effects on body temperature regulation

Chronic exposure to phenobarbital at a 21-22 degrees C ambient temperature produced marked hypothermia in C57BL/6J male mice, to which functional tolerance gradually developed over a 6.5 day intoxication period. Soon after phenobarbital withdrawal, marked hypothermia again developed, reaching its maximal extent at a time when tremors, convulsions on handling and Straub tail were at their peak frequency. When these mice were placed in a 34 degrees C ambient environment, which prevents the hypothermia, these withdrawal signs were eliminated or greatly reduced in frequency compared to mice at 22 degrees C, whereas the incidence of tonic-clonic seizures was not significantly affected. Core body temperature was found to correlate significantly with the degree of gross intoxication during the intoxication phase and with the withdrawal signs of tremor and Straub tail after withdrawal of the drug. When mice were given a choice between a 23 and a 35 degrees C environment at times of maximal hypothermia, their choice often served to maintain the hypothermic state rather than to reduce it. These results suggest that some of the signs of withdrawal (tremor and Straub tail) may be (in part) secondary responses to a primary dysfunction, which is thermoregulatory in nature.