Acute Tolerance to the Hypnotic Effect of Morphine in Rats

To demonstrate the development of acute tolerance to the hypnotic effects of morphine, loss and recovery of the righting reflex with a constant-rate morphine infusion was studied in rats. In one group of animals, brain and serum concentrations of morphine were detected (radioimmunoassay) at the time of loss of the righting reflex, and in another group, at the time of the reflex recovery. The morphine infusion at a constant rate of 14 mg.kg-1.h-1 caused a loss of the righting reflex in all animals that was achieved by 2.5 h. However, this level of response could not be maintained, and at 5 h it began to decline. All animals recovered the righting reflex by the ninth hour, despite the continuing morphine infusion. The morphine brain and serum levels at the times of loss and recovery of the righting reflex were not different. The results suggest a development of acute tolerance to the hypnotic effect of morphine, which is determined primarily by pharmacodynamic mechanisms.