Anesthesia & Analgesia

Skip Navigation LinksHome > December 2007 - Volume 105 - Issue 6 > Mechanisms of Morphine Enhancement of Spontaneous Seizure Ac...
Anesthesia & Analgesia:
doi: 10.1213/01.ane.0000287675.15225.0b
Neurosurgical Anesthesia: Research Report

Mechanisms of Morphine Enhancement of Spontaneous Seizure Activity

Saboory, Ehsan PhD*; Derchansky, Miron PhD*†; Ismaili, Mohammed PhD*; Jahromi, Shokrollah S. PhD*; Brull, Richard MD, FRCPC‡; Carlen, Peter L. MD, FRCPC*†§; El Beheiry, Hossam MBBCh, PhD, FRCPC*‡

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BACKGROUND: High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors.

METHODS: Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons.

RESULTS: Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 μM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 μM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective μ and κ opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, δ opioid receptor ligands did not have an effect.

CONCLUSIONS: The proseizure effect of morphine is mediated through selective stimulation of μ and κ opiate receptors but not the activation of the δ receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.

© 2007 International Anesthesia Research Society


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