title: Endocannabinoids mediate the glucocorticoid-induced inhibition of excitatory synaptic transmission to dorsal raphe serotonin neurons.
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.
authors.affiliation: Research Institute on Addictions, University at Buffalo, 1021 Main Street, Buffalo, NY 14203, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Roh-Yu
authors.initials: RY
authors.lastname: Shen
authors.forename: Samir
authors.initials: S
authors.lastname: Haj-Dahmane
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D059326:Serotonergic Neurons / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D063388:Endocannabinoids; D005938:Glucocorticoids; D043562:Receptors, G-Protein-Coupled; D018698:Glutamic Acid; D003907:Dexamethasone; D003345:Corticosterone