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Journal of Pharmacology And Experimental Therapeutics, Vol. 185, Issue 2, 328-335, 1973
Copyright © 1973 by American Society for Pharmacology and Experimental Therapeutics

BIOGENIC AMINES AND NARCOTIC EFFECTS. II. SEROTONIN TURNOVER IN THE RAT AFTER ACUTE AND CHRONIC MORPHINE ADMINISTRATION

G. G. YARBROUGH 1, D. M. BUXBAUM 1, and E. SANDERS-BUSH 1

1 Department of Pharmacology, Vanderbilt University School of Medicine and Tennessee Neuropsychiatric Institute, Nashville, Tennessee

As determined by nonisotopic and isotopic techniques, the turnover of cerebral serotonin (5-HT) is enhanced in Sprague-Dawley rats after a single injection of 16 or 32 mg/kg of morphine. Low and intermediate doses of morphine (e.g., 4 and 8 mg/kg) fail to alter whole-brain 5-HT metabolism. Chronic administration of 16 mg/kg of morphine results in the development of tolerance to the increase in 5-HT turnover observed afer a single injection. Naloxone pretreatment blocks the increase in 5-HT turnover induced by 16 mg/kg of morphine. Wistar rats showed a similar increase in 5-HT turnover after 16 mg/kg of morphine. The increase in 5-HT turnover after acute morphine administration was not reflected by an increase in in vitro tryptophan hydroxylase activity. Moreover, tryptophan hydroxylase activity was not altered by chronic morphine treatment. These observations suggest that 5-HT synthesis is stimulated by acute morphine administration and tolerance develops to this effect with repeated exposure to the drug. The possible significance of these data are discussed in relation to the role of 5-HT in narcotic-induced motor effects.

Submitted on January 28, 1972
Accepted on December 21, 1972




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