Morphine-induced downregulation of mu-opioid receptors in neonatal rat brain.
Chronic administration of morphine to pre- and postnatal rats produced a marked decrease in brain mu-opioid receptor density with-out change in receptor affinity. No significant changes in delta- or kappa-receptors were observed. This downregulation was accompanied by tolerance to the analgesic actions of morphine. In neonates exposed to morphine from postnatal day one, mu-receptor number was significantly depressed until postnatal day 8, then increased gradually to control levels by day 14 of treatment. Longer treatment produced no further change in opioid receptors. These data represent the first demonstration of in vivo downregulation of brain mu-opioid receptors following morphine administration and provide evidence for a unique plasticity of the immature opioid receptor system.
Tempel
A
A
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
Habas
J
J
Paredes
W
W
Barr
G A
GA
D000375:Aging; D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D003692:Delayed-Action Preparations; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D007700:Kinetics; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu
D003692:Delayed-Action Preparations; D004745:Enkephalins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine