ObjectiveThe optimal target of deep brain stimulation (DBS) for treating intractable epilepsy is still undefined. Cumulative studies suggest that the mediodorsal thalamic nucleus (MD) is involved in seizure activity, the purpose of this study was to investigate the effect of high frequency stimulation in MD on pentylenetetrazole (PTZ)-induced seizures in rats. MethodsThe experimental rats (Male Sprague-Dawley rats 280-350 g) were all provided by Experimental Animal Center, Zhejiang Academy of Medical Science, Hangzhou, China. The rats were given unilateral or bilateral stimulation of the MD at 100 Hz (HFS group) and sham stimulation, others were given unilateral stimulation of the MD at 1 Hz (LFS group). EEGs in the cortex and seizure behavior were recorded with the Neuroscan system at the same time. ResultsNeither LFS nor HFS of the MD changed the latency to the first spikes or EEG manifestations for stage 3 and stage 5 seizures; animals receiving unilateral or bilateral HFS of the MD decreased the number of stage 5 EEG seizure synchronized with the convulsive episodes; LFS and sham stimulation showed multiple periods of continuous spikes which accompanied stage 5 or stage 4 seizures. HFS of unilateral or bilateral MD, but not LFS, decreased the seizure stage, the number of clonic movement episodes, and the duration of acute PTZ-induced seizures. The average latency to onset of myoclonic jerks did not differ among groups. Unilateral and bilateral HFS of the MD had a similar antiepileptic effect. ConclusionHFS of the MD may be of value as a new antiepileptic approach for patients with generalized epilepsy, besides, the seizure model, should be fully considered in clinical application.