BIOCHEMICAL CORRELATES OF MORPHINE WITHDRAWAL .1. CHARACTERIZATION IN THE ADRENAL-MEDULLA AND LOCUS CERULEUS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 233  (2) , 333-338
Abstract
Adrenal catecholamines and their synthesizing enzymes were monitored during morphine treatment and after naloxone-precipitated morphine withdrawal in the rat. At 2 and 6 h of withdrawal epinephrine content was reduced to .apprx. 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. Epinephrine is selectively released from the adrenal medulla during naloxone-precipitated morphine withdrawal in the rat. This release has both a direct and a centrally mediated component. The possible mechanisms underlying these biochemical changes are discussed.

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