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Journal of Pharmacology And Experimental Therapeutics, Vol. 180, Issue 3, 547-557, 1972
Copyright © 1972 by American Society for Pharmacology and Experimental Therapeutics

MORPHINE-INDUCED INCREASES IN THE INCORPORATION OF 14C-TYROSINE INTO 14C-DOPAMINE AND 14C-NOREPINEPHRINE IN THE MOUSE BRAIN: ANTAGONISM BY NALOXONE AND TOLERANCE

C. B. SMITH 1, M. I. SHELDON 1, J. H. BEDNARCZYK 1, and J. E. VILLARREAL 1

1 Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

The effects of morphine and levorphanol upon the incorporation of 14C-tyrosine into 14C-catecholamines in various tissues of the mouse were determined. Morphine, 100 mg/kg, increased the synthesis of 14C-catecholamines in mouse brain and adrenals but not in heart or spleen. Morphine, 100 mg/kg, had no effect upon the free tyrosine or 14C-tyrosine content of the mouse brain. d-Amphetamine, 10 mg/kg, did not increase the incorporation of 14C-tyrosine into 14C-eatecholamines in these four tissues. Morphine, 100 mg/kg, and levorphanol, 10 mg/kg, nearly doubled the incorporation of 14C-tyrosine into both 14C-dopamine and 14C-norepinephrine in the brain. Morphine-induced increases in 14C-catecholamine synthesis occurred in the cerebral cortex, diencephalon, striatum, brainstem and cerebellum. After repeated administration of either morphine, 100 mg/kg, or levorphanol, 30 mg/kg, tolerance and cross-tolerance developed to the effects of these drugs upon the synthesis of 14C-dopamine and 14C-norepinephrine. Naloxone, a specific morphine antagonist, blocked the effects of morphine upon 14C-dopamine and 14C-norepinephrine synthesis. The present study suggests that the catecholamines may play an important role in the mechanisms by which narcotic analgesics produce certain specific effects.

Submitted on March 11, 1971
Accepted on November 15, 1971




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