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Resolvin E1/E2 ameliorate lipopolysaccharide-induced depression-like behaviors via ChemR23

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Abstract

Rationale

Resolvins are bioactive lipid mediators that are generated from docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). We recently demonstrated that the DHA-derived resolvins D1 and D2 exert antidepressant effects. However, whether the EPA-derived resolvins E1 (RvE1) and E2 (RvE2) produce antidepressant effects is not clear.

Objectives

We examined the antidepressant effects of RvE1/RvE2 in a murine lipopolysaccharide (LPS)-induced depression model using the tail suspension and forced swim tests. RvE1/RvE2 reportedly possesses both chemerin receptor ChemR23 agonistic activity and leukotriene B4 receptor BLT1 antagonistic activity. Therefore, we investigated the receptor involved in its antidepressant effects. We also examined the roles of the mammalian target of rapamycin complex 1 (mTORC1) in the antidepressant effect of RvE1 as well as the effects of RvE1 infusions into the medial prefrontal cortex (mPFC) and hippocampal dentate gyrus (DG) on LPS-induced depression-like behaviors.

Results

Intracerebroventricular infusions of RvE1 (1 ng)/RvE2 (10 ng) produced significant antidepressant effects. An intracerebroventricular infusion of chemerin (500 ng), but not U75302 (a BLT1 antagonist; 10 or 50 ng), produced antidepressant effects. Intraperitoneal rapamycin (an mTORC1 inhibitor; 10 mg/kg) blocked the antidepressant effect of intracerebroventricular RvE1. Bilateral intra-mPFC and intra-DG infusions of RvE1 (50 pg/side) exerted antidepressant effects.

Conclusions

The results of this study demonstrate that (1) RvE1/RvE2 produce antidepressant effects likely via ChemR23, (2) mTORC1 signaling mediates the antidepressant effect of RvE1, and (3) mPFC and DG are the key brain regions involved in these actions. RvE1/RvE2 and their receptors may be promising targets for the development of novel antidepressants.

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Authors and Affiliations

  1. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan

    Satoshi Deyama, Kento Shimoda, Hiroe Suzuki, Yuka Ishikawa, Natsuko Hitora-Imamura, Soichiro Ide & Masabumi Minami

  2. Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan

    Satoshi Deyama & Katsuyuki Kaneda

  3. Laboratory of Organic Chemistry for Drug Development, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan

    Kohei Ishimura, Hayato Fukuda & Satoshi Shuto

  4. Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan

    Soichiro Ide

  5. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan

    Masamichi Satoh

Authors
  1. Satoshi Deyama
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  2. Kento Shimoda
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  3. Hiroe Suzuki
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  4. Yuka Ishikawa
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  5. Kohei Ishimura
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  6. Hayato Fukuda
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  7. Natsuko Hitora-Imamura
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  8. Soichiro Ide
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  9. Masamichi Satoh
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  10. Katsuyuki Kaneda
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  11. Satoshi Shuto
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  12. Masabumi Minami
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Correspondence to Masabumi Minami.

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Deyama, S., Shimoda, K., Suzuki, H. et al. Resolvin E1/E2 ameliorate lipopolysaccharide-induced depression-like behaviors via ChemR23. Psychopharmacology 235, 329–336 (2018). https://doi.org/10.1007/s00213-017-4774-7

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  • DOI: https://doi.org/10.1007/s00213-017-4774-7

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