Glucocorticoid exerts its non-genomic effect on IPSC by activation of a phospholipase C-dependent pathway in prefrontal cortex of rats

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Key pointsActivation of the membrane-binding glucocorticoid receptors enhances spontaneous GABAergic activity and elicits intermittent burst activity in hippocampus and prefrontal cortex of rats.The burst activities are abolished in the presence of tetrodotoxin.The time courses of the effects are different between hippocampus and prefrontal cortex, the onset in the latter being much slower.The nitric oxide (NO) pathway is present and endogenously activated in prefrontal cortex.The effects of membrane-binding glucocorticoid receptor on GABAergic synaptic transmission are mediated by both NO and phospholipase C–diacylglycerol pathways in hippocampus and prefrontal cortex of rats.In response to stressor, the brain activates a comprehensive stress system. Among others, this stress system causes release of glucocorticoids that also feed back to the brain. Glucocorticoids affect brain function by activation of both delayed, genomic and rapid, non-genomic mechanisms in rodents. Here we report that application of the potent glucocorticoid receptor agonist dexamethasone (DEX) caused a rapid increase of spontaneous and miniature inhibitory postsynaptic currents (IPSCs) and elicited intermittent burst activities through a non-genomic pathway, involving membrane-located receptors. The onset of the rapid effect in prefrontal cortex (PFC, <15 min) was much slower than in hippocampus (<5 min). The intermittent burst activities were abolished in the presence of TTX. Furthermore, the nitric oxide (NO) pathway was present and endogenously activated in PFC. Part of the rapid DEX effect in PFC remained after blocking NO-sensitive guanylyl cyclase that was due to activation of a phospholipase C–diacylglycerol-dependent signalling pathway. Thus, our data demonstrated that glucocorticoids could rapidly enhance IPSCs and evoke burst activities by activation of at least two different signalling pathways in hippocampus and PFC of rats.

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