Time course of the distribution of morphine in brain regions and spinal cord after intravenous injection to spontaneously hypertensive and normotensive Wistar-Kyoto rats.
Previous studies from this laboratory have demonstrated that the analgesic and hyperthermic effects of morphine were found to be greater in spontaneously hypertensive (SHR) rats than in normotensive Wistar-Kyoto (WKY) rats. The enhanced response to morphine could not be explained on the basis of any of the pharmacokinetic parameters of morphine in the serum. In order to determine the possible contribution of altered distribution of morphine in the central nervous system in the differences in the pharmacological response to morphine in the two strains, the time course of the distribution of morphine was determined in brain regions and spinal cord after its i.v. administration. SHR and WKY rats were injected with morphine (10 mg/kg). At various times (5, 30, 60, 120 and 360 min) after the injection of morphine, brain regions (hypothalamus, cortex, hippocampus, midbrain, pons and medulla, striatum and amygdala) and spinal cord were collected. The level of morphine in the tissues was determined by using a highly sensitive and specific radioimmunoassay method. Five minutes after morphine injection, the concentration of morphine was the highest in the spinal cord. Among the brain regions, the highest concentration of morphine was in the hypothalamus and the lowest in the amygdala. In all the brain regions and spinal cord, the concentration of morphine was significantly higher in the SHR than in the WKY rats. Similar effects were observed at 30, 60 and 120 min after morphine injection. At 360 min, the hypothalamus, cortex and spinal cord of the SHR rats had higher concentrations of morphine than the WKY rats, but the other regions did not show differences in the morphine levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Bhargava
H N
HN
Department of Pharmacodynamics, University of Illinois, Chicago.
Villar
V M
VM
Rahmani
N H
NH
Larsen
A K
AK
D000698:Analgesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013116:Spinal Cord / Q000378:metabolism; D014018:Tissue Distribution
D009020:Morphine