Biochemical correlates of morphine withdrawal. 1. Characterization in the adrenal medulla and locus ceruleus.
Adrenal catecholamines and their synthesizing enzymes were monitored during morphine treatment and after naloxone-precipitated morphine withdrawal in the rat. At 2 and 6 hr of withdrawal epinephrine content was reduced to approximately 50 and 45% of control. Five days after withdrawal a significant overshoot in adrenal epinephrine concentration was observed. Morphine treatment increased adrenal tyrosine hydroxylase activity to 160% of control. Precipitation of withdrawal with naloxone further increased adrenal tyrosine hydroxylase activity to 240% of control after 1 day; the enzyme activity returned to control values at day 7. Similar effects, but of lesser magnitude, were observed with locus ceruleus tyrosine hydroxylase activity. No increase in adrenal dopamine-beta-hydroxylase activity was seen until day 3 of withdrawal and this activity peaked at 5 days to 160% of control values. Adrenal phenylethanolamine-N-methyltransferase activity was unchanged during the time course studied. Splanchnicotomy caused depletion of adrenal epinephrine to 60% of control. Morphine withdrawal in these animals caused a further (23%) decrease in epinephrine content. These data show that epinephrine is selectively released from the adrenal medulla during naloxone-precipitated morphine withdrawal in the rat and that this release has both a direct and a centrally mediated component. The possible mechanisms underlying these biochemical changes are discussed.
DiStefano
P S
PS
Brown
O M
OM
D000313:Adrenal Medulla / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008125:Locus Coeruleus / Q000201:enzymology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000201:enzymology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D009270:Naloxone; D009020:Morphine; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase