Kong, Chang Hyeon Lee, Jin Woo Jeon, Mijin Kang, Woo Chang Kim, Min Seo Park, Keontae Bae, Ho Jung Park, Se Jin Jung, Seo Yun Kim, Su -Nam Kleinfelter, Benjamin Kim, Ji-Woon Ryu, Jong Hoon 2024-05-23T06:00:04Z 2024-05-23T06:00:04Z 2024-05-23 2024-06 0278-5846 https://pubs.kist.re.kr/handle/201004/149888 Post-traumatic stress disorder (PTSD) is a mental illness that can occur in individuals who have experienced trauma. Current treatments for PTSD, typically serotonin reuptake inhibitors, have limited effectiveness for patients and often cause serious adverse effects. Therefore, a novel class of treatment with better pharmacological profile is necessary. D-Pinitol has been reported to be effective for depression and anxiety disorders, but there are no reports associated with PTSD. In the present study, we investigated the effects of D-pinitol in a mouse model of PTSD induced by a single prolonged stress (SPS) protocol. We examined the therapeutic effects of D-pinitol on emotional and cognitive impairments in the SPS mouse model. We also investigated the effects of D-pinitol on fear memory formation. Mineralocorticoid receptor transactivation assay, Western blot, and quantitative PCR were employed to investigate how D-pinitol exerts its pharmacological activities. D-Pinitol ameliorated PTSD-like behaviors in a SPS mouse model. D-Pinitol also normalized the increased mRNA expression levels and protein levels of the mineralocorticoid receptor in the amygdala. A mineralocorticoid receptor agonist reversed the effects of D-pinitol on fear extinction and recall, and the antagonistic property of Dpinitol against the mineralocorticoid receptor was confirmed in vitro. Our findings suggest that D-pinitol could serve as a potential therapeutic agent for PTSD due to its antagonistic effect on the mineralocorticoid receptor. English Elsevier BV D-Pinitol mitigates post-traumatic stress disorder-like behaviors induced by single prolonged stress in mice through mineralocorticoid receptor antagonism Article 10.1016/j.pnpbp.2024.110990 1 Progress in Neuro-Psychopharmacology and Biological Psychiatry, v.132 Progress in Neuro-Psychopharmacology and Biological Psychiatry 132 N scie scopus 001219316700001 2-s2.0-85188431681 Clinical Neurology Neurosciences Pharmacology & Pharmacy Psychiatry Neurosciences & Neurology Pharmacology & Pharmacy Psychiatry Article ANIMAL-MODELS AMYGDALA DYSFUNCTION FLUOXETINE ANXIETY TIME FEAR Post -traumatic stress disorder D-Pinitol Single prolonged stress Amygdala Glucocorticoid receptor Mineralocorticoid receptor