Tolerance and sensitization to the biphasic effects of low doses of morphine in the hamster

Two experiments investigated the dose and time related effects of morphine sulfate on wheel running behavior in golden Syrian hamsters. In Experiment 1, within-subject comparisons were made of the acute effects of 5, 20, and 40 mg/kg doses of morphine sulfate on running wheel activity. Compared with saline, morphine produced a dose related decrease in activity followed by a dose related recovery. At the lowest dose, the time effect curve was biphasic, with sustained hyperactivity following the recovery. In Experiment 2, the effects of low doses of morphine sulfate (0.5, 1.0, 2.5, 5.0 mg/kg) on running wheel activity were monitored for three days. Biphasic time effect patterns were evident at each dose: An initial period of hypoactivity was followed by recovery and subsequent hyperactivity. Moreover, repeated administration produced both tolerance and sensitization to morphine's effects on activity. Implications for mechanisms underlying the biphasic response pattern are discussed.