Locomotor activity after recovery from hypnosis: midazolam-morphine versus midazolam

This study was performed to test the hypothesis that sedation after recovery from pharmacologic hypnosis is less pronounced if hypnosis is induced with a midazolam-morphine combination compared with midazolam administered alone. Loss of the righting reflex was used as an index for the hypnotic effect and reduction of locomotor activity as an index for the sedative effect. One group of rats received midazolam (20 mg/kg i.v) and another group an equipotent (in relation to the hypnotic ef.fect) combination of midazolam (4 mg/kg i.v.) and morphine (1.3 mg/kg i.v.). The duration of loss of the righting reflex in the midazolam and midazolam-morphine groups was 30 +/- 3 and 28 +/- 2 min, respectively (mean +/- SE). The difference between the groups in locomotor activity after recovery from hypnosis was very pronounced. The locomotor activity in the midazolam-morphine group at 1 and 2 h was seven and five times greater, respectively, than in the midazolam group (P < 0.005). The profound difference in locomotor activity for the two treatment groups was explained on the basis of the difference in the outcomes of midazolam-morphine interactions with regard to hypnosis (synergism) and sedation (summation). When the animals recovered from hypnosis, the synergism of the drug interaction ceased to be a contributing factor.