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Role of endogenous opioids and histamine in morphine induced emesis
Abstract:
The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report.
Insights
This study reveals that both opioid and histamine systems contribute to morphine-induced vomiting in dogs, acting via the chemoreceptor trigger zone (CTZ). Blocking these systems with antagonists like naloxone and mepyramine prevents vomiting.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Morphine is known to induce emesis (vomiting).
- The precise mechanisms, particularly the involvement of the opioid and histaminergic systems, require further elucidation.
Purpose of the Study:
- To investigate the roles of the opioid and histaminergic systems in morphine-induced emesis in dogs.
- To determine the involvement of the chemoreceptor trigger zone (CTZ) in this response.
Main Methods:
- Morphine was administered intraventricularly (icv) to dogs to induce emesis.
- The effect of CTZ ablation on morphine-induced emesis was assessed.
- Dogs were pretreated with opioid antagonist naloxone and histamine antagonists (mepyramine, metiamide, cimetidine) before morphine administration.
- Cerebrospinal fluid (CSF) histamine levels were measured after morphine administration.
Main Results:
- Morphine (25 µg, icv) reliably induced emesis with a mean latency of 195 ± 29 sec.
- CTZ ablation abolished morphine-induced emesis.
- Pretreatment with naloxone, mepyramine, metiamide, and cimetidine protected against morphine-induced emesis.
- CSF histamine levels significantly increased 5 minutes post-morphine administration.
- High-dose naloxone (1600 µg, icv) induced emesis independently of the CTZ.
Conclusions:
- Both endogenous opioid and histamine systems play a significant role in morphine-induced emesis.
- The chemoreceptor trigger zone (CTZ) is a critical site for mediating morphine-induced vomiting.
- Histamine release in the cerebrospinal fluid is associated with morphine administration.