Sustained nerve-mediated contractions of guinea-pig ileum during morphine withdrawal by washout
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S M Johnson1, C M Humphreys, M Costa
1Department of Physiology, School of Medicine, Flinders University, Bedford Park, South Australia.
Abstract:
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 microM). 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.
Insights
Morphine withdrawal in guinea-pig ilea causes spontaneous contractions. This washout-induced excitation involves cholinergic neurons and is sustained, offering a model for studying withdrawal signs.
Area of Science:
- Pharmacology
- Neuroscience
- Gastroenterology
Background:
- Opioid withdrawal is a complex physiological response.
- The guinea-pig ileum is a model for studying opioid effects on smooth muscle.
- Understanding withdrawal mechanisms is crucial for managing opioid dependence.
Purpose of the Study:
- To investigate the effects of morphine withdrawal by washout in guinea-pig ilea.
- To characterize the neuronal pathways involved in morphine withdrawal-induced contractions.
- To establish an in vitro model for studying sustained withdrawal phenomena.
Main Methods:
- Guinea-pigs were pretreated with morphine pellets.
- Longitudinal muscle-myenteric plexus preparations were isolated.
- In vitro experiments were conducted in modified Krebs solution with and without morphine.
- Effects of tetrodotoxin (TTX), hyoscine, and hexamethonium were assessed.
Main Results:
- Morphine washout induced marked spontaneous contractions in ileal preparations.
- These contractions were significantly reduced by TTX and hyoscine, but not hexamethonium.
- The observed excitation primarily involved cholinergic myenteric motor neurons.
- Withdrawal-induced contractions were sustained for up to 5 hours.
Conclusions:
- Morphine washout provides a robust in vitro model for studying opioid withdrawal.
- The findings highlight the role of cholinergic myenteric neurons in withdrawal-induced ileal contractions.
- This model is suitable for investigating the mechanisms of sustained withdrawal signs in the ileum.