{"doi":"10.1016/j.molpha.2025.100058","title":"Corticosterone stimulates synthesis of 2-arachidonoylglycerol via putative membrane-bound glucocorticoid receptors and inhibits GABA release via CB1 cannabinoid receptors in the ventrolateral periaqueductal gray","abstract":"The ventrolateral periaqueductal gray (vlPAG) plays a critical role in pain modulation. GABAergic neurotransmission within the vlPAG regulates the descending pain pathway. This study investigates the mechanisms through which corticosterone (CORT) modulates GABA release in the vlPAG via putative membrane-associated glucocorticoid receptors (mbGRs). Superfusion of CORT decreases evoked inhibitory postsynaptic currents in a mbGR- and CB1 cannabinoid receptor (CB1R)-dependent manner. Using a depolarization-induced suppression of inhibition protocol to test the effects of CORT on the endocannabinoid system, we find that CORT-mediated signaling enhances 2-arachidonoylglycerol (2-AG) synthesis that is inhibited by the diacylglycerol lipase inhibitor, DO34. CORT prolongs CB1R activation through a Gα s and protein kinase A-dependent pathway, while early DSI-initiated endocannabinoid activation of CB1Rs is independent of protein kinase A. These results highlight the critical role of CORT in the vlPAG in engaging endocannabinoid pathways to inhibit GABA release. The results indicate that CORT activation of putative mbGRs promote activation of the descending pain modulatory pathway through CB1R-mediated inhibition of GABA release in the vlPAG.","journal":"Molecular Pharmacology","year":2025,"id":528375,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":395394,"name":"Courtney A. Bouchet","orcid":"0000-0002-0630-0392","position":1,"is_corresponding":false},{"id":1406709,"name":"Lorenzo C. Patti","orcid":null,"position":2,"is_corresponding":false},{"id":777290,"name":"Kylie B. McPherson","orcid":"0000-0002-5196-098X","position":3,"is_corresponding":false},{"id":1406710,"name":"Bethany S Boston","orcid":null,"position":4,"is_corresponding":false},{"id":504023,"name":"David C. Jewett","orcid":null,"position":5,"is_corresponding":false},{"id":251363,"name":"Susan Ingram","orcid":"0000-0003-1371-8532","position":6,"is_corresponding":false},{"id":878089,"name":"Basile Coutens","orcid":null,"position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T02:50:48.492873Z","pmid":"40729946","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}