Hypersensitivity of the opioid-tolerant guinea pig ileum to electrical stimulation after abrupt agonist removal.
Studies were initiated on the myenteric plexus of the guinea pig ileum to ascertain whether a supersensitive response by abrupt withdrawal could be elicited after tolerance development to opioids. After an optimal twitch response to a given electrical stimulus was established and its height measured, the mean concentration of an opioid to inhibit half maximally the response (IC50) was determined. Subsequently, the tissues were rendered tolerant by incubating with 1x to 5x the IC50 of the agonist for two hours. The agonist was then removed by thorough washing with Ringer solution and the twitch height to the same electrical stimulation was remeasured. The increase in twitch height after washing over that before incubation provided an index of the degree of hypersensitivity of the tolerant-dependent tissue. The degree of hypersensitivity was found to increase in relation to the concentration of morphine. Stereo-specificity of agonist action was evinced by a hypersensitive response to levorphanol and not to dextrorphan. The development of hypersensitivity was blocked by naloxone and by chloramphenicol. Ethylketocyclazocine, a k ligand, did not show a hypersensitivity response. It is concluded that physical dependence on u-opioids can be developed in vitro and that it can be quantified by a super-sensitivity response.
D000818:Animals; D004361:Drug Tolerance; D004558:Electric Stimulation; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome
D009294:Narcotics; D009020:Morphine