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Evidence for serotonergic system involvement in the effect of morphine on gastrointestinal motility in the rat
1Department of Pharmacology, Faculty of Medicine, Medical Sciences University of Shahid-Beheshti, Evin, Tehran, Iran.
Abstract:
1. Intestinal motility was measured by the transit of charcoal meal through the small intestine of the rat. 2. Morphine given subcutaneously induced a reduction in the gastrointestinal transit (GIT), and the response was dose-dependent (0.1-2.5 mg/kg). 3. The inhibitory effect of morphine was antagonized by prior subcutaneous administration of naloxone (1 mg/kg). 4. Depletion of serotonergic neurons by para-chlorophenylalanine (100 mg/kg, ip, 3 days) completely abolished the inhibitory action of morphine. 5. Methysergide (5 mg/kg, sc) and ketanserin (5 mg/kg, sc) also reduced the morphine effect. 6. Destruction of serotonergic neurones by intracerebroventricular injection of 5,7-dihydroxytryptamine (20 mu/kg) abolished the effect of morphine. 7. These observations provide some evidence for the involvement of a central serotonergic system in the effect of morphine on gastrointestinal motility.
Insights
Morphine reduces gastrointestinal transit in rats, an effect dependent on central serotonergic neurons. This action is blocked by naloxone and specific serotonin antagonists, indicating a key role for serotonin.
Area of Science:
- Neuropharmacology
- Gastroenterology
- Physiology
Background:
- Opioids like morphine significantly impact gastrointestinal motility.
- The precise mechanisms underlying morphine's effects on the gut remain under investigation.
- Serotonergic systems are known modulators of various physiological processes, including gut function.
Purpose of the Study:
- To investigate the role of the central serotonergic system in mediating morphine's inhibitory effects on gastrointestinal transit.
- To determine if serotonin depletion or antagonism alters morphine's impact on gut motility.
Main Methods:
- Gastrointestinal transit (GIT) in rats was measured using a charcoal meal assay.
- Morphine's effect on GIT was assessed dose-dependently.
- Pharmacological interventions included naloxone (opioid antagonist), para-chlorophenylalanine (serotonin depletion), methysergide and ketanserin (serotonin antagonists), and 5,7-dihydroxytryptamine (serotonin neurotoxin).
Main Results:
- Morphine administration dose-dependently reduced gastrointestinal transit.
- The inhibitory effect of morphine on GIT was abolished by para-chlorophenylalanine and 5,7-dihydroxytryptamine, indicating a role for serotonergic neurons.
- Naloxone, methysergide, and ketanserin antagonized or reduced the effects of morphine on gastrointestinal transit.
Conclusions:
- Central serotonergic pathways are critically involved in mediating the inhibitory effects of morphine on gastrointestinal motility.
- These findings highlight a neurochemical link between opioid action and the serotonergic system in regulating gut function.