{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:12:17Z","timestamp":1792447937212,"version":"4.5.0"},"reference-count":99,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"The Israel Science Foundation (ISF)","doi-asserted-by":"publisher","award":["993\/20"],"award-info":[{"award-number":["993\/20"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>MDMA-assisted psychotherapy has shown potential as an effective treatment for post-traumatic stress disorder (PTSD). Preclinical studies involving rodents have demonstrated that MDMA can facilitate the extinction of fear memories. It has been noted that MDMA impacts oxytocin neurons and pro-inflammatory cytokines. Thus, the aim of this study was to explore the role of oxytocinergic signaling and neuroinflammatory markers in the therapeutic effects of MDMA. To achieve this, male rats were subjected to a model of PTSD involving exposure to shock and situational reminders. MDMA was microinjected into the medial prefrontal cortex (mPFC) before extinction training, followed by behavioral tests assessing activity levels, anxiety, and social function. Our findings indicate that MDMA treatment facilitated fear extinction and mitigated the shock-induced increase in freezing, as well as deficits in social behavior. Shock exposure led to altered expression of the gene coding for OXT-R and neuroinflammation in the mPFC and basolateral amygdala (BLA), which were restored by MDMA treatment. Importantly, the OXT-R antagonist L-368,899 prevented MDMA\u2019s therapeutic effects on extinction and freezing behavior. In conclusion, MDMA\u2019s therapeutic effects in the PTSD model are associated with alterations in OXT-R expression and neuroinflammation, and MDMA\u2019s effects on extinction and anxiety may be mediated by oxytocinergic signaling.<\/jats:p>","DOI":"10.3390\/ph17070846","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T03:42:30Z","timestamp":1719546150000},"page":"846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Examining the Role of Oxytocinergic Signaling and Neuroinflammatory Markers in the Therapeutic Effects of MDMA in a Rat Model for PTSD"],"prefix":"10.3390","volume":"17","author":[{"given":"Haron","family":"Avgana","sequence":"first","affiliation":[{"name":"Department of Psychology, School of Psychological Sciences, University of Haifa, Haifa 3498838, Israel"},{"name":"The Integrated Brain and Behavior Research Center (IBBRC), University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roni Shira","family":"Toledano","sequence":"additional","affiliation":[{"name":"Department of Psychology, School of Psychological Sciences, University of Haifa, Haifa 3498838, Israel"},{"name":"The Integrated Brain and Behavior Research Center (IBBRC), University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-5953","authenticated-orcid":false,"given":"Irit","family":"Akirav","sequence":"additional","affiliation":[{"name":"Department of Psychology, School of Psychological Sciences, University of Haifa, Haifa 3498838, Israel"},{"name":"The Integrated Brain and Behavior Research Center (IBBRC), University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/s41591-021-01336-3","article-title":"MDMA-assisted therapy for severe PTSD: A randomized, double-blind, placebo-controlled phase 3 study","volume":"27","author":"Mitchell","year":"2021","journal-title":"Nat. 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