Related Experiment Videos
Compound 48/80, a histamine-depleting agent, blocks the protective effect of morphine against electroconvulsive shock
C H Karadag1, D Dokmeci, T Dost
1Department of Pharmacology, Faculty of Medicine, Trakya University, Edirne, Turkey. karadag@turk.net
Abstract:
We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES) in mice, and this effect is antagonized by histamine H1-receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4, and 4 mg/kg on day 5, twice daily, ip) to deplete mast cell contents. Morphine (0.001-10 mg/kg, ip; N = 20) produced a dose-dependent anticonvulsive effect against MES seizure in mice with non-depleted mast cells, whereas it did not exert any anticonvulsive effect in mice with depleted mast cells. These results indicate that morphine produces its anticonvulsive effect against maximal electroconvulsive shock in mice by liberating histamine from mast cells.
Insights
Morphine
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Morphine exhibits anticonvulsive properties against maximal electroconvulsive shock (MES) in mice.
- Histamine H1-receptor antagonists counteract morphine's anticonvulsive effects.
- Brain histamine resides in neurons and mast cells; morphine influences histamine turnover and release.
Purpose of the Study:
- To investigate the role of mast cell-derived histamine in morphine's anticonvulsive effect against MES seizures.
- To determine if histamine release from mast cells mediates morphine's protective action.
Main Methods:
- Mice were treated with compound 48/80 to deplete mast cell histamine.
- Morphine's anticonvulsive efficacy against MES was assessed in both mast cell-depleted and non-depleted mice.
- Dose-dependent effects of morphine were evaluated.
Main Results:
- Morphine demonstrated a dose-dependent anticonvulsive effect against MES in mice with intact mast cells.
- This anticonvulsive effect was abolished in mice with depleted mast cells.
- Compound 48/80 successfully depleted mast cell histamine.
Conclusions:
- Morphine's anticonvulsive effect against MES in mice is mediated by the release of histamine from mast cells.
- Mast cell degranulation is a key mechanism underlying morphine's anticonvulsant action in this model.
- Targeting mast cell histamine release could be a strategy for modulating morphine's effects.