Dose-dependent effects of morphine on hippocampal seizure

Abstract

Opiates have complex effects on seizure thresholds as these substances have both anti and proconvulsive actions in the mammalian brain. A reduction of inhibitory synaptic activity or enhancement of excitatory synaptic activity would be expected to trigger a seizure. This study is designed to determine how morphine and naloxone affect seizures induced by a low Mg2+ perfusate in the whole, intact hippocampus of mouse in vitro. In this research, C57BL/ 6 mice (P11-17) were used. Intact hippocampal structures were carefully dissected and incubated for at least 1 hour prior to recording. The tissues were perfused by low Mg2+ (0.2 mM)-ACSF at a rate of 3 ml/min. Morphine sulfate was used in various doses (10, 30, 100, 200 µM) as an opioid receptor agonist, while naloxone (5 and 10 µM) was utilized as an antagonist of these receptors. Various concentrations of morphine sulfate showed variable effects on whole hippocampus activity: Morphine (30 and 100 µM) noticeably elongated the length of epileptiform activity, while decreasing the frequency of the tonic stage of seizures. Morphine (200 µM) attenuated the hippocampal seizure activities. Low concentrations (5 µM) of naloxone did not show any significant effect on hippocampal activity, but higher concentrations of naloxone (10 µM) depressed both interictal and ictal like events. When combining perfusion with morphine (10, 30, 100, and 200) and naloxone (10 µM), both interictal and ictal-like events were depressed. Our results indicate that morphine in therapeutic doses of 30 µM may enhance seizure activity and its use in epileptic patients should be considered with caution. Conversely, naloxone has anticonvulsant actions.