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 morphin e produced greater analgesic but lower hyperthermic responses to morph ine in 24-week-old rats in comparison to 8-week-old rats. The differen tial pharmacological responses to morphine could not solely be attribu ted to the pharmacokinetic parameters, namely area under the serum mor phine concentration-time curve, serum levels of morphine extrapolated to zero time, half-life, mean residence time, apparent volume of distr ibution at the steady state, terminal rate constant and total body cle arance of morphine in serum. In order to determine whether the differe nces in pharmacological responses to morphine in rats from two age gro ups are related to differential distribution of morphine in the centra l nervous system, in the present study, the time course of the distrib ution of morphine in brain regions (hypothalamus, hippocampus, cortex, pons and medulla, amygdala, midbrain and corpus striatum), spinal cor d and serum following intravenous injection of 10 mg/kg dose to 8- and 24-week-old male Sprague-Dawley rats was determined. Morphine injecte d intravenously produced a greater analgesic but less intense hyperthe rmic effect in 24-week-old rats in comparison to 8-week-old rats. In m ost of the brain regions and spinal cord, with few exceptions, the con centration of morphine was found to be greater in 24-week-old rats tha n in 8-week-old rats. Similarly, the ratio of the concentration of mor phine in brain region or spinal cord to serum was significantly higher in rats from the older age group. The studies demonstrate- that the a ltered pharmacological responses to intravenously administered morphin e to rats of differing ages may be related to the higher concentration of morphine in the central nervous system of older rats, which in tur n may be related to the differences in the blood-brain barrier to morp hine in the two age groups.