Regional and temporal regulation and role of somatostatin receptor subtypes in the mouse brain following systemic kainate-induced acute seizures

•Acute seizure activity differently regulates expression of somatostatin receptors.•Among subtypes, epileptic activity increases only Sst2 expression in the amygdala.•Sst2 upregulation in the amygdala precedes that in the hippocampus.•Sst2 knockdown causes neuronal hyperexcitability and delayed seizure recovery. Somatostatin reduces neuronal excitability via somatostatin receptors (Sst1-Sst5) and inhibits seizure activity. However, the expression status of the Sst subtypes in epileptic mice and their role in the antiepileptic effects of somatostatin remain unclear. Here, we show that the Sst subtypes are regulated differently by epileptic neuronal activity in mice. Systemic kainate injection rapidly and transiently elevated the Sst2 and Sst3 mRNA and reduced Sst1 and Sst4 mRNA in the hippocampus; however, among all the subtypes, only Sst2 mRNA was increased in the excitatory neurons of the basolateral amygdala, accompanied by a decrease in the level of Sst2 protein. Following kainate administration, recovery from seizure was delayed by reduced expression of Sst2 in the basolateral amygdala, but not in the dentate gyrus of the hippocampus; higher expression levels of Bdnf, a neuronal activity marker, were observed in both conditions. These results suggest that Sst2 contributes to seizure termination by feedback inhibition in the amygdala. This could be a potential therapeutic target for acute seizures.