Acute and chronic effects of morphine on Low-Mg ACSF-induced epileptiform activity during infancy in mice hippocampal slices.

Interaction of morphine and seizure is complex. Mouse brain hippocampal slices were used to estimate how acute and chronic morphine treatment alters the low-magnesium artificial cerebrospinal fluid (LM-ACSF)-induced seizure activity. Hippocampal slices were taken from the normal and morphine-treated mice. The normal mice received saline while the other group (morphine-treated mice) received morphine daily for 5 consecutive days. Saline/morphine administration was performed subcutaneously (s.c, 0.1 mL) at postnatal days 14-18. Hippocampal slices of all animals were perfused with LM-ACSF followed by different morphine concentrations (0, 10, 100, and 1000 μM) or naloxone (10 μM). Changes in the spike count were considered as indices for quantifying the seizure activity in the slices. In hippocampus of both groups perfused with 10 or 1000 μM morphine, epileptiform activity was suppressed while it was potentiated at 100 μM morphine. The excitatory effect of morphine at 100 μM was stronger in normal mice (acute exposure) than in dependent mice (chronic exposure). Naloxone suppressed the epileptiform activities in both groups. Suppressive effect of naloxone was more significant in morphine-treated mice than in normal mice. The seizure activity in morphine-dependent mice was more labile than that of normal mice. It can be concluded that morphine had a biphasic effect on LM-ACSF-induced epileptiform activities in both groups. The occurrence of seizure was comparable in acute and chronic exposure of morphine but strength of the effect was considerably robust in normal mice. The down regulation of opioid receptors in chronic exposure is likely to be responsible for these differences.