Effect of age on acute morphine response in the rat.

The importance of age as an experimental variable in the evaluation of the analgesic, thermic, and respiratory depressant effects to morphine was studied in male rats one and one-half, six, and ten months of age. Significant age-related responses were observed in both the analgesic and thermic responses to morphine. Also, following a dose of 30 mg/kg morphine, animals six and ten months of age exhibited significantly higher plasma levels of morphine, a slower decline in both plasma and brain levels of morphine, and lower brain/plasma ratios of morphine indicating possible age-related changes in metabolism, excretion, and the blood-brain barrier. The dose of morphine which produced respiratory depression was significantly higher in the youngest age group; this was accompanied by higher brain levels of morphine in this group. These studies illustrate the importance of age as an experimental variable in the evaluation of drugs.