Involvement of 5-HT7 receptors in the pathogenesis of temporal lobe epilepsy

The 5-hydroxytryptamine 7 (5-HT7) receptor is the most recently classified member of the serotonin receptor family. The localization of 5-HT7 receptors and the biological activity of its ligands have suggested that 5-HT7 receptors might be involved in the pathogenesis of epilepsy. In the present study, we investigated the correlation between temporal lobe epilepsy and 5-HT7 receptors using pilocarpine-induced rat models of temporal lobe epilepsy and surgical samples of temporal neocortex from intractable epilepsy patients. An analysis of electroencephalogram (EEG) and behavioral changes before and after the treatment of SB269970 hydrochloride (a selective 5-HT7 receptor antagonist, 10 mg/kg, i.p.) and AS19 (a selective 5-HT7 receptor agonist, 10 mg/kg, s.c.) demonstrated that in epileptic rats the activation of 5-HT7 receptors could increase the number of seizures, which could be reduced by a 5-HT7 receptor antagonist. Moreover, the expression of 5-HT7 receptors was higher in the epilepsy group compared with the nonepileptic group in both rat and human brain tissues. The present results suggested that 5-HT7 receptors participate in the pathogenesis of temporal lobe epilepsy, and a 5-HT7 receptor antagonist may be used as a therapeutic alternative for temporal lobe epilepsy.