Aim: 

Somatostatin-14 (SRIF) reduces hippocampal epileptiform activity but the contribution of its each specific receptors (sst1-5) is poorly understood. We have focused on the role of sst1 and sst2 in mediating SRIF modulation of epilepsy using mouse hippocampal slices.

Methods: 

The model of Mg²⁺-free medium/4-aminopyridine- (0Mg²⁺/4AP-) induced interictal-like activity in hippocampal slices was used for both electrophysiology and measurements of glutamate release using HPLC ESI-MS.

Results: 

With extracellular recordings, we demonstrated that the sst1 agonist CH-275, but not the sst2 agonist octreotide, mimics the SRIF-induced reduction of epilepsy. sst1 blockade with the antagonist SRA-880 reverses the CH-275-mediated inhibition of epileptiform activity. In addition, SRIF and CH-275 are without effect in the hippocampus of sst1 KO mice. With intracellular recordings, we found that SRIF, acting on sst1, reduces both NMDA- and AMPA / kainate-postsynaptic potentials, whereas it increases GABAA-postsynaptic potentials. Measurements of glutamate release demonstrated that SRIF inhibits the increase in glutamate production induced by 0Mg²⁺/4AP.

Conclusion: 

Our findings represent the first demonstration of an important role of sst1 in mediating anticonvulsant effects of SRIF. As shown by our results, SRIF acts not only at the postsynaptic level by decreasing neuronal responsiveness to glutamate but also presynaptically by regulating glutamate release.