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Endocannabinoids mediate the glucocorticoid‐induced inhibition of excitatory synaptic transmission to dorsal raphe serotonin neurons
Author(s) -
Wang Jue,
Shen RohYu,
HajDahmane Samir
Publication year - 2012
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2012.238659
Subject(s) - glutamatergic , neurotransmission , dorsal raphe nucleus , neuroscience , excitatory postsynaptic potential , chemistry , glutamate receptor , biology , medicine , serotonin , endocrinology , inhibitory postsynaptic potential , serotonergic , receptor , biochemistry
Key points• The modulation of the serotonin system by glucocorticoids plays a central role in the regulation of stress responses. However, the mechanisms by which glucocorticoids regulate the excitability of dorsal raphe serotonin neurons remain unknown. • In this study, we show that glucocorticoids rapidly inhibit glutamatergic synaptic transmission to serotonin neurons by reducing glutamate release. • The rapid inhibition of glutamate release is not signalled by classical intracellular glucocorticoid receptors, but rather by putative membrane‐located G‐protein‐coupled receptors. • Activation of the membrane‐located G‐protein‐coupled receptors increases endocannabinoid signalling, which in turn mediates the inhibition of glutamatergic transmission in the dorsal raphe. • In the dorsal raphe, glucocorticoids increase endocannabinoid tone by inhibiting cyclooxygenase‐2.Abstract Glucocorticoids play a critical role in the modulation of stress responses by controlling the function of the serotonin (5‐HT) system. However, the precise effects of glucocorticoids on the excitability of dorsal raphe (DR) 5‐HT neurons remain unknown. In this study, we investigated the effects of glucocorticoids on excitatory synaptic transmission to putative DR 5‐HT neurons. We found that corticosterone or the synthetic glucocorticoid agonist dexamethasone rapidly suppressed glutamatergic synaptic transmission to DR 5‐HT neurons by inhibiting glutamate release in the DR. This inhibitory effect was mimicked by membrane‐impermeable glucocorticoids, indicating the involvement of membrane‐located corticosteroid receptors. The glucocorticoid‐induced inhibition of glutamatergic transmission was mediated by the activation of postsynaptic G‐protein‐coupled receptors and signalled by retrograde endocannabinoid (eCB) messengers. Examination of the downstream mechanisms revealed that glucocorticoids enhance eCB signalling via an inhibition of cyclooxygenase‐2. Together, these findings unravel a novel mechanism by which glucocorticoids control the excitability of DR 5‐HT neurons and provide new insight into the rapid effects of stress hormones on the function of the 5‐HT system.