Sustained nerve-mediated contractions of guinea-pig ileum during morphine withdrawal by washout

The effects of morphine withdrawal by washout were examined in ilea from guinea-pigs pretreated by subcutaneous implantation of two pellets, each containing 155 mg morphine. One week later preparations of the longitudinal muscle-myenteric plexus were set up in vitro in a modified Krebs solution containing morphine (1 μM). Within 5-15 min after washing in morphine-free Krebs, the preparations exhibited marked spontaneous contractions which became maximal after 20-60 min. The contractions resulting from morphine washout were greatly reduced by TTX and by hyoscine but not by hexamethonium, suggesting that excitation involved predominantly the cholinergic myenteric motor neurons, and was thus similar to that underlying the contraction induced by naloxone. In contrast to the naloxone-induced contractions, however, those resulting from morphine washout were well sustained during periods of recording up to 5 h. Morphine washout therefore provides conditions suitable for investigating the mechanisms underlying the variety of withdrawal signs observed in the ileum in vitro.