Anticonvulsant actions of cortistatin-14 are abolished by selective sst2 and sst3 antagonism.

Cortistatin-14 (CST-14), a recently discovered neuropeptide, was shown in one report to protect against kainate-induced seizures and can interact with SST receptors(sst1-sst5).
We used in vivo microdialysis and telemetry-based electrocorticography(ECoG) in rats and administered CST-14(0.1µM-1µM-10µM) in the presence and absence of highly selective antagonists for sst2 and sst3 receptor subtypes via intrahippocampal(IH) administration. Seizures were evoked by IH pilocapine perfusion(10mM,40min) and seizure severity was assessed using a behavioural scoring system. Moreover, behavioural seizure severity assessment was verified with ECoG in at least 2 rats of each test group treated with CST-14.
ECoG recordings of the rats treated with 0.1µM CST-14 showed epileptic discharges following pilocarpine perfusion. In none of the rats epileptic discharges were recorded during treatment with 1µM and 10µM CST-14.
Furthermore, we showed that the CST-14(1µM)-mediated anticonvulsant actions were reversed in the presence of a selective sst2 receptor antagonist Cyanamid154806(0.1µM) or a selective sst3 receptor antagonist SST3-ODN-8(0.1µM). IH perfusion of the selective sst2 or the selective sst3 receptor antagonists alone did not affect the pilocarpine-induced seizure severity.