TIME-COURSE OF THE DISTRIBUTION OF MORPHINE IN BRAIN-REGIONS, SPINAL-CORD AND SERUM FOLLOWING INTRAVENOUS-INJECTION TO RATS OF DIFFERING AGES

Previously it was demonstrated that intravenously administered morphine produced greater analgesic but lower hyperthermic responses to morphine in 24-week-old rats in comparison to 8-week-old rats. The differential pharmacological responses to morphine could not solely be attributed to the pharmacokinetic parameters, namely area under the serum morphine concentration-time curve, serum levels of morphine extrapolated to zero time, half-life, mean residence time, apparent volume of distribution at the steady state, terminal rate constant and total body clearance of morphine in serum. In order to determine whether the differences in pharmacological responses to morphine in rats from two age groups are related to differential distribution of morphine in the central nervous system, in the present study, the time course of the distribution of morphine in brain regions (hypothalamus, hippocampus, cortex, pons and medulla, amygdala, midbrain and corpus striatum), spinal cord and serum following intravenous injection of 10 mg/kg dose to 8- and 24-week-old male Sprague-Dawley rats was determined. Morphine injected intravenously produced a greater analgesic but less intense hyperthermic effect in 24-week-old rats in comparison to 8-week-old rats. In most of the brain regions and spinal cord, with few exceptions, the concentration of morphine was found to be greater in 24-week-old rats than in 8-week-old rats. Similarly, the ratio of the concentration of morphine in brain region or spinal cord to serum was significantly higher in rats from the older age group. The studies demonstrate- that the altered pharmacological responses to intravenously administered morphine to rats of differing ages may be related to the higher concentration of morphine in the central nervous system of older rats, which in turn may be related to the differences in the blood-brain barrier to morphine in the two age groups.