Abstract
THE finding that theophylline, which inhibits brain cyclic AMP phosphodiesterase1, produces a “quasi-morphine abstinence syndrome” that is intensified by naloxone and suppressed by heroin2 suggested that the real morphine abstinence syndrome may be associated with increased activity of a brain cyclic nucleotide. A suitable phosphodiesterase inhibitor would therefore heighten and a stimulant of phosphodiesterase would lower the intensity of real morphine abstinence signs. To test this, we administered such drugs to morphine-dependent rats shortly before withdrawal was precipitated with naloxone, so that the drugs would act only during the expression of abstinence. As these experiments indicated that the abstinence syndrome is largely associated with increased cyclic nucleotide activity, we attempted to identify the nucleotide by intracere-broventricular injection of cyclic nucleotides. These experiments indicated that cyclic AMP rather than cyclic GMP was primarily involved.
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COLLIER, H., FRANCIS, D. Morphine abstinence is associated with increased brain cyclic AMP. Nature 255, 159–162 (1975). https://doi.org/10.1038/255159b0
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DOI: https://doi.org/10.1038/255159b0
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