2. Academic Validation
  3. Sex Differences in Antidepressant Effect of Sertraline in Transgenic Mouse Models

Sex Differences in Antidepressant Effect of Sertraline in Transgenic Mouse Models

  • Front Cell Neurosci. 2019 Feb 1;13:24. doi: 10.3389/fncel.2019.00024.
Lei Ma 1 2,  Yong Xu 1 3,  Wei Jiang 4,  Yuhong Li 5 6,  Xinzhu Zhang 6,  Gang Wang 1 2,  Rena Li 1 5 6
Affiliations

Affiliations

  • 1 The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
  • 2 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
  • 3 Qingdao Municipal Hospital, Qingdao, China.
  • 4 School of Life Sciences, University of Science and Technology of China, Hefei, China.
  • 5 Center for Hormone Advanced Science and Education, Roskamp Institute, Sarasota, FL, United States.
  • 6 Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
PMID: 30778289 DOI: 10.3389/fncel.2019.00024
Abstract

The main purpose of this study is to explore sex differences in the antidepressant effect of sertraline in genetic knockout or overexpression estrogen-synthesizing Enzyme aromatase (Ar) gene mouse models in the forced swim test (FST). Our results demonstrated a significant reduction of depression-like behavior in the mice with overexpression of brain aromatase (Thy1-Ar) compared to sex- and age-matched Ar+/- mice or wild type control mice. Using HPLC analysis, we also found an association between the brain estrogen-related antidepressive behavior and the regulation of serotonin (5-HT) system. Interestingly, a single dose administration of sertraline (10 mg/kg, i.p.) induced reduction of immobility time was found in all genotypes, except male Ar+/- mice. While the underlying mechanisms of sex-specific response on antidepressive effect of sertraline remain to be investigated, our data showed that female mice appear to be more sensitive to sertraline-induced changes of 5-HT system than male mice in the prefrontal cortex (PFC) and the hippocampus (HPC). Further investigation of sex-specific effect of brain estrogen on antidepressant is needed.

Keywords

5-HT; DA; estrogen; sertraline; sex difference.

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