PS138. Early life stress increases stress vulnerability through BDNF gene epigenetic changes in the rat hippocampus
s 47 Experiment 2. FSL and FRL animals received single injections of CBD (10 or 30 mg/Kg, ip) ketamine (10 mg/Kg, ip) or vehicle and were submitted to the forced swimming test (FST) 1h later. Results: Experiment 1. Acute treatment with CBD (30 mg/Kg) immediately after the pretest, but not with imipramine, significantly reduced the number of escape failures during the test, an antidepressant like effect similar to chronic treatment with imipramine (ANOVA, p<0.05) Experiment 2. Single injection of CBD (30 mg/Kg, ip) reduced the immobility in FSL and FRL animals, similarly to ketamine (10 mg/Kg, ip) (ANOVA, p<0.05) Conclusion: Acute treatment with CBD is able to induce antidepressant like effect in the learned helplessness and FSL/FRL models. These results reinforce the proposal that CBD could induce acute antidepressant effects in humans. Financial support: FAPESP, Capes, CNPq, Danish Research Council PS138 Early life stress increases stress vulnerability through BDNF gene epigenetic changes in the rat hippocampus Mi Kyoung Seo 1, Nguyen Ngoc Ly 2, Chan Hong Lee 1, Hye Yeon Cho 1, Cheol Min Choi 2, Le Hoa Nhu 2, Jung Goo Lee 1,2,3, Bong Ju Lee 3, Gyung Mee Kim 3, Baik Seok Kee 4, Sung Woo Park 1,2* and Young Hoon Kim 1,2,3* 1 Paik Institute for Clinical Research, 2 Department of health science and technology, Graduate School of Inje University, 3 Department of Psychiatry, School of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea and 4 Department of Psychiatry, School of Medicine, Chungang University, Seoul, Republic of Korea. Abstract Objective: Early life stress (ELS) exerts long lasting epigenetic influences on the brain and makes an individual susceptible to later depression. It is poorly understood whether ELS and subsequent adult chronic stress modulate epigenetic mechanisms. We examined the epigenetic mechanisms of the BDNF gene in the hippocampus, which may underlie stress vulnerability to postnatal maternal separation (MS) and adult restraint stress (RS) Methods: Rat pups were separated from their dams (3 h/day from P1 P21) When the pups reached adulthood (8 weeks old) we introduced RS (2 h/day for 3 weeks) followed by escitalopram treatment. Results: We showed that both the MS and RS groups expressed reduced levels of total and exon IV BDNF mRNA. Furthermore, RS potentiated MS induced decreases in these expression levels. Similarly, both the MS and RS groups showed decreased levels of acetylated histone H3 and H4 at BDNF promoter IV, and RS exacerbated MS induced decreases of H3 and H4 acetylation. Both the MS and RS groups had increased MeCP2 levels at BDNF promoter IV, as well as increased HDAC5 mRNA, and the combination of MS and RS exerted a greater effect on these parameters than did RS alone. In the forced swimming test, the immobility time of the MS+RS group was significantly higher than that of the RS group. Additionally, chronic escitalopram treatment recovered these alterations. Conclusion: Our results suggest that postnatal MS and subsequent adult RS modulate epigenetic changes in the BDNF gene, and that these changes may be related to behavioral phenotype. These epigenetic mechanisms are involved in escitalopram action.
International Journal of Neuropsychopharmacology