Anticonvulsant actions have already widely been proven for somatostatin-14 (SST-14). The contribution of the (SST1-SST5) receptors in these anticonvulsant actions is poorly understood and many interspecies differences have been shown. Recent studies pointed to the involvement of the SST4 receptors in regulating hippocampal excitability, although both SST4-mediated pro-and anticonvulsant effects have been demonstrated (1,2). To investigate the importance of this receptor in rats, we used L-803,087, a selective SST4 receptor agonist. In vivo microdialysis in male albino Wistar rats was used for intrahippocampal drug administration. Seizures were evoked by intrahippocampal pilocarpine perfusion (10mM, 40 min) and seizure severity was assessed using a behavioural scoring system. We showed that intrahippocampal administration of L-803,087 (100nM) was able to prevent pilocarpine convulsions. Coperfusion experiments of this agonist with cyanamid 154806 (CYN), a selective SST2 receptor antagonist, or SST3-ODN8, a selective SST3 receptor antagonist clearly reversed the anticonvulsant actions of L-803,087. CYN or SST3-ODN8 perfusion alone did not significantly alter the pilocarpine induced seizures. These observations point to an important involvement of the SST2 or SST3 receptor in mediating the anticonvulsant actions of the SST4 receptor. A functional coupling between SST2 and SST4 receptors was also previously shown in mice, although in that study, SST4 showed proconvulsant properties (2). These findings suggest a major role for the SST4 receptor in mediating the anticonvulsant actions of SST-14 in rats. Once again the importance of interspecies differences within this research domain is emphasized.

References: 

(1) Qiu et al. (2008) J Neurosc 28:3567, (2) Moneta et al. (2002) J Neurosc 16:843