Effects of opiate receptor agonists and antagonists on spontaneuse seizure activity in hipocampal slices

Opiates have complex effects on seizure activity. They have both anti-and proconvulsive effects depend on their concentration. Low doses of morphine have anticonvulsant effects, while high doses have proconvulsant effects. Sudden morphine withdrawal results in short-term proconvulsant effects. In the present, the effects of opioid receptors agonists and antagonists on spontaneous seizure activity in epileptogenic hippocampal slices were evaluated. Hippocampal slices (400 µm) were prepared from young Wistar rats (P15-25). Seizure activity was induced by continuous perfusion of the slices with low-Mg2+ ACSF. Extra cellular recordings were performed in the hippocampal CA1 pyramidal cell layer. Seizure activity was quantified by measuring the amplitude and duration of the ictal events as well as their number after and prior to the application of the agonists and antagonists of the opioid receptors. In addition, the numbers of interictal spikes were determined to complement the analysis of seizure discharges before and after drug application. Our results show that DAMGO and Dyn-A (10 μM), as μ and κ-opioid receptor agonist respectively, cause a significant increase in the incidence and amplitude & duration of ictal activity and these effects were completely reversed following the appilcation of B-FNA and nor-BNI (10 μM) as μ and κ opioid receptor antagonist respectively. DPDPE (10μM), a selective δ-opioid receptor agonist, caused a significant decrease in the incidence and duration of ictal activity and these effects were completely reversed by the addition of NTI (10μM), a selective δ opioid receptor antagonist. Our finding showed that epileptic effects of morphine probably are established by activation of μ and κ opioid receptors and due to the activation of δ opioid receptor, morphine produces antiepileptic effects.