PHARMACOLOGICAL CHARACTERIZATION OF OPIATE PHYSICAL DEPENDENCE IN THE ISOLATED ILEUM OF THE GUINEA‐PIG

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Abstract
Physical dependence was produced in ilea from naive guinea‐pigs by exposure of the tissues to different opiates for logarithmically‐spaced periods of time (20–320 min). The responsiveness of the tissue to naloxone, as indicated by a strong contracture of the ileum, was enhanced in contrast to that found in intestines not exposed to opiates. The dose‐response curves to naloxone obtained in tissues individually exposed to different opiates showed that their relative potency in increasing sensitivity to naloxone was as follows: levorphan > morphine > Met‐enkephalin > nalorphine > pentazocine. The naloxone‐induced response was dose‐dependent and was directly related to the opiate concentration and length of exposure. Dextrorphan, the inactive isomer of levorphan, did not increase the responsiveness of the tissues to the narcotic antagonist, indicating that the phenomenon is stereospecific. The naloxone‐induced contraction in ilea exposed for 320 min to morphine (1 × 10−6 m) was not prevented or suppressed by the administration of a large dose of morphine (1 × 10 −5 m) before or immediately after the naloxone challenge. The evidence presented here shows that a phenomenon resembling in vivo opiate physical dependence can be acutely produced in vitro with pharmacological characteristics similar to other naloxone‐induced abstinence effects.