Risperidone induced DNA methylation changes in dopamine receptor and stathmin genes in mice exposed to social defeat stress

Fatima Zahra Rami ^{1, 2}, Thong Ba Nguyen ^{1, 2}, Young-Eun Oh ^{1, 2}, Maryam Karamikheirabad ^{1, 2}, Thi-Hung Le ^{1, 2}, Young-Chul Chung ^{1, 2*}

¹Department of Psychiatry, Jeonbuk National University Medical School, Jeonju Korea, ²Research Institute of Clinical Medicine of Jeonbuk National University and Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea

Received: May 12, 2021; Revised: July 11, 2021; Accepted: July 12, 2021; Published online: July 12, 2021.

Abstract: Objectives: Understanding complex epigenetic mechanisms is necessary to fully elucidate the effects of antipsychotic drug. This study investigated DNA methylation and mRNA expression levels of dopamine D2 and D1 receptor (Drd2 and Drd1, respectively), nuclear receptor subfamily 3, group C, member 1 (Nr3c1) and stathmin 1 (Stmn1) in brain regions of mice exposed to social defeat stress (SDS) and effects of risperidone on altered methylation and mRNA expression levels induced by SDS .
Methods: Following SDS for 10 days, risperidone (0.2 mg/kg) or vehicle was administered to adult mice for 7 days. Brain tissues from the prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY) were processed to measure methylation and mRNA levels of Drd2, Drd1, Nr3c1 and Stmn1 using pyrosequencing and real time-PCR.
Results: We found altered methylation status of Nr3c1 and Stmn1 in the HIP and AMY of mice exposed to SDS. These changes were reversed by risperidone treatment. In addition, different methylation patterns of Drd2 and Drd1 in the PFC and AMY between defeated and control mice were identified with risperidone treatment.
Conclusions: These findings suggest that risperidone can cause epigenetic changes in Drd2, Drd1, Nr3c1 and Stmn1 in defeated mice. These changes could be epigenetic mechanisms underlying antipsychotic efficacy.; Keywords: Social defeat stress, Nr3c1, Risperidone, Stmn1, DNA methylation, mRNA expression, Drd2, Drd1

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