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Heroin, 6-acetylmorphine and morphine effects on threshold for rewarding and aversive brain stimulation.

C. Hubner,Conan Kornetsky

Published 1992 in Journal of Pharmacology and Experimental Therapeutics

ABSTRACT

Studies investigating the reinforcing and analgesic activity of heroin and morphine have found that heroin is a more potent compound. The rapid deacetylation of heroin to 6-acetylmorphine and morphine raises questions concerning the underlying mechanism responsible for this difference in potency. The present series of experiments addressed this issue by examining, in the rat, the relative potency of heroin and its active metabolites, 6-acetylmorphine and morphine, to lower the threshold for rewarding stimulation of the medial forebrain bundle and raise the threshold for aversive stimulation of the mesencephalic reticular formation. Reward and escape thresholds were determined by using a modification of the psychophysical method of limits. Heroin was found to be approximately 40 times more potent than morphine in lowering the reward threshold and approximately 6.5 times more potent in raising the escape threshold. 6-Acetylmorphine and heroin were approximately equipotent in producing significant effects on the threshold for both rewarding and aversive brain stimulation. These findings suggest that heroin's increased potency when compared to morphine may be due, in part, to the activity of 6-acetylmorphine.

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