Interaction of pentobarbital and morphine in the tail-flick test performed on rats: synergism at the spinal and antagonism at the supraspinal level.

The dose-dependence of the effects and interaction of pentobarbital and morphine administered by intrathecal (i.t.) and intraperitoneal (i.p.) injection was determined in experiments performed on the tail-flick response to radiant heat applied to the tail of rats. I.t. injection of pentobarbital and morphine, and i.p. injection of morphine depressed the tail-flick response, while i.p. injection of pentobarbital facilitated it. The effects caused by i.t. injection of the two drugs depended on the intensity of noxious stimulation. When pentobarbital and morphine were administered in combination by i.t. injection, they potentiated each other's effect. After i.p. injection of pentobarbital and morphine the facilitatory effect of pentobarbital was abolished and the antinociceptive effect of morphine was enhanced. The results reveal a synergism of the actions of pentobarbital and morphine at the spinal level and an antagonism at the supraspinal level which is probably of the functional type.