Dexmedetomidine inhibits epileptiform activity in rat hippocampal slices

Purpose: Our study aimed to investigate the effects of dexmedetomidine on basal synaptic transmission in the rat hippocampus. We also examined dexmedetomidine in an animal epilepsy model, with further investigation into the role of specific antagonists on the alpha-2 adrenoceptors and the imidazoline receptors. Methods: All of the experiments used the CA1 region of hippocampal brain slices prepared from Sprague-Dawley rats. Epileptiform discharges were induced by perfusing Mg2+-free artificial cerebrospinal fluid (ACSF). We first investigated the effects of dexmedetomidine on population spike (PS) amplitudes and field excitatory postsynaptic potentials (fEPSP) amplitudes in normal ACSF. We then investigated the effects of dexmedetomidine on the amplitudes of the first three PSs and the discharge duration in Mg2+-free ACSF or in normal ACSF containing 10 μM bicuculline. Results: Dexmedetomidine depressed PS amplitudes and fEPSP without affecting the paired-pulse inhibition in normal ACSF. Dexmedetomidine inhibited the epileptiform activity produced by Mg2+-free ACSF in a dose-dependent manner. Dexmedetomidine completely abolished the epileptiform activity induced by bicuculline. In the presence of yohimbine, dexmedetomidine had no significant effect on epileptiform activity. In the presence of efaroxan and idazoxan, dexmedetomidine significantly (P < 0.05) increased and slightly attenuated the amplitude of the epileptiform activity, respectively. Conclusion: These results suggest that dexmedetomidine depresses the glutamatergic excitatory synaptic transmission, but may not affect the inhibitory synaptic transmission mediated via the GABAA-receptor in rat hippocampal slices. The anticonvulsant action of dexmedetomidine is mediated mainly via alpha-2 adrenoceptors. In addition, imidazoline type 1 and type 2 receptors are also involved in the effect of dexmedetomidine on the epileptiform activity.