Morphine physical dependence in the hibernator: central nervous system mechanisms underlying the development of dependence remain functional during depression induced by pentobarbital anesthesia.

Earlier work suggested that adaptive mechanisms of the hibernating brain may also block the development of morphine physical dependence. To test an alternate view that CNS depression itself might be the major factor in the failure of dependence to develop, we compared the strength of dependence produced by morphine (two 75-mg pellets, s.c.) given for 12 hr in the presence, versus in the absence, of continuous pentobarbital anesthesia in nonhibernating ground squirrels (Citellus lateralis) and, in addition, in rats. Dependence was measured by the naloxone (5 mg/kg, s.c.) evoked abstinence syndrome in the awake state. The results demonstrated that pentobarbital-induced general anesthesia does not significantly reduce the development of morphine dependence in either species. We conclude that CNS depression alone does not account for the hibernation-related reduction in morphine physical dependence.