Letter | Published:

Morphine withdrawal response and central cholinergic activity

Naturevolume 257pages131132 (1975) | Download Citation



MOST of the different neurotransmitter systems have been implicated in opiate withdrawal. Frederickson and Pinsky1 suggested a primary role for acetylcholine (ACh) in both the development and the expression of dependence on morphine but the specific role of cholinergic mechanisms in opiate withdrawal is not yet clear and deserves further attention. The hypothesis of the role of ACh in the expression of withdrawal phenomena, on which most earlier experiments were based, was that of the ‘cholinergic excess’, first postulated by Paton2. Tests of this hypothesis in various laboratories have, however, produced conflicting results and thus confusion rather than clarification of the role of cholinergic mechanisms in the withdrawal syndrome3–9. Unfortunately, many such studies have neglected to differentiate between peripheral interference with expression and central interference with initiation of the signs of withdrawal by the various drugs studied. Our experiments were designed to eliminate this particular factor, which has contributed to much of the conflict. The results clearly illustrate the confounding effect of failure to separate peripheral from central cholinergic effects and suggest that the exact opposite of the cholinergic excess theory is the actual nature of the central cholinergic role in the morphine withdrawal syndrome.

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  1. Department of Pharmacology, The Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, 46206



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