Development and loss of tolerance to morphine in the rat.

The development of a differential tolerance to morphine was investigated with respect to the mean effective dose, the threshold dose of tolerance, the degree of tolerance after a fixed dose, and the speed of tolerance loss. The mean effective doses, the threshold doses of tolerance, and the degree of tolerance differed considerably from effect to effect, whereas in all tests tolerance loss remained the same. The mean effective doses were not correlated to threshold doses of tolerance, degree of tolerance, or to the loss of tolerance, but a strong correlation exists between threshold doses of tolerance and degree of tolerance to all effects measured. Consequences of these results upon current theories of tolerance are discussed.