Respiratory Depressant Effects of Morphine on the Central Nervous System of the Infant Rat

Abstract

The dose of morphine hydrochloride (1.5 mg/kg) necessary to achieve 50% depression of the ventilatory rates was identical in both 5- and 30-day-old rats. However, at equivalent blood levels, drug concentrations in the brain stem, cerebral hemispheres, and cerebrospinal fluid of the infant rat were approximately 2-fold greater than those found in the older animal. With increased doses (3 mg/kg), the respiratory rate of the infant rat decreased to 15% of resting values, in association with an increased rate of morphine accumulation in the cerebrospinal fluid. Although older rats showed only a 50% depression of the respiratory rate at doses as high as 6 mg/kg, the LD50 (16 mg/kg) was 73% lower than found for the infant animal. In the usual therapeutic dose range, the infant rat appears to be no more sensitive to the toxic effects of morphine than the older animal.