THE IMPACT OF STRESS AND GLUCOCORTICOIDS ON GLUTAMATE SYNAPSES IN CEREBRAL CORTEX

Dysfunction of the glutamatergic system has been associated with the pathophysiology of stress-related neuropsychatric disorders. Nevertheless, the mechanisms whereby stress and its mediators affect neurotransmission are still unknown. We have previously showed that acute footshock stress induces a marked increase of depolarization-evoked glutamate release from prefrontal and frontal cortex synaptosomes, via glucocorticoid receptor and presynaptic SNARE complex accumulation. Main aim of the present work was to compare the ex vivo effects of acute stress with those of in vitro application of corticosterone, to analyze whether acute effect of stress on glutamatergic transmission is mediated by rapid synaptic action of corticosterone. We found that acute stress increases both the readily releasable pool (RRP) of vesicles and depolarization-evoked glutamate release, while application in vitro of corticosterone rapidly increases the RRP, an effect dependent on synaptic receptors, but not glutamate release. Therefore, the results obtained suggest that the increase of the RRP size induced by acute stress is promoted by a local action of corticosterone on (presumably membrane-located) synaptic receptors. However, the lack of increase of depolarization-dependent glutamate release, after in vitro incubation of isolated synaptosomes with corticosterone, suggests that additional mediators released by postsynaptic neurons and/or glia, are necessary to trigger release. The combined results of this study give more insight into the basic mechanisms whereby behavioral stress affects excitatory transmission in the forebrain.