PT  - JOURNAL ARTICLE
AU  - P S DiStefano
AU  - O M Brown
TI  - Biochemical correlates of morphine withdrawal. 1. Characterization in the adrenal medulla and locus ceruleus.
DP  - 1985 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 333--338
VI  - 233
IP  - 2
4099  - http://jpet.aspetjournals.org/content/233/2/333.short
4100  - http://jpet.aspetjournals.org/content/233/2/333.full
SO  - J Pharmacol Exp Ther1985 May 01; 233
AB  - 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.