Cellular and Molecular Neurobiology

, Volume 37, Issue 4, pp 595–606 | Cite as

Contribution of Hippocampal 5-HT3 Receptors in Hippocampal Autophagy and Extinction of Conditioned Fear Responses after a Single Prolonged Stress Exposure in Rats

  • Zhong-Min Wu
  • Li-Hua Yang
  • Rong Cui
  • Gui-Lian Ni
  • Feng-Tian Wu
  • Yong Liang
Original Research


One of the hypotheses about the pathogenesis of posttraumatic stress disorder (PTSD) is the dysfunction of serotonin (5-HT) neurotransmission. While certain 5-HT receptor subtypes are likely critical for the symptoms of PTSD, few studies have examined the role of 5-HT3 receptor in the development of PTSD, even though 5-HT3 receptor is critical for contextual fear extinction and anxiety-like behavior. Therefore, we hypothesized that stimulation of 5-HT3 receptor in the dorsal hippocampus (DH) could prevent hippocampal autophagy and the development of PTSD-like behavior in animals. To this end, we infused SR57227, selective 5-HT3 agonist, into the DH after a single prolonged stress (SPS) treatment in rats. Three weeks later, we evaluated the effects of this pharmacological treatment on anxiety-related behaviors and extinction of contextual fear memory. We also accessed hippocampal autophagy and the expression of 5-HT3A subunit, Beclin-1, LC3-I, and LC3-II in the DH. We found that SPS treatment did not alter anxiety-related behaviors but prolonged the extinction of contextual fear memory, and such a behavioral phenomenon was correlated with increased hippocampal autophagy, decreased 5-HT3A expression, and increased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. Furthermore, intraDH infusions of SR57227 dose-dependently promoted the extinction of contextual fear memory, prevented hippocampal autophagy, and decreased expression of Beclin-1 and LC3-II/LC3-I ratio in the DH. These results indicated that 5-HT3 receptor in the hippocampus may play a critical role in the pathogenesis of hippocampal autophagy, and is likely involved in the pathophysiology of PTSD.


5-HT3 receptor Hippocampal autophagy Posttraumatic stress disorder Conditioned fear response Memory extinction 



We thank Professor Marong Fang for his valuable suggestions on this paper.


This work was supported by Zhejiang Provincial Science and Technology Department of Public Welfare Technology Application Project (2014C37026).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Zhong-Min Wu
    • 1
    • 3
  • Li-Hua Yang
    • 2
  • Rong Cui
    • 3
  • Gui-Lian Ni
    • 3
  • Feng-Tian Wu
    • 4
  • Yong Liang
    • 1
  1. 1.Department of AnatomyMedical College of Taizhou UniversityTaizhouChina
  2. 2.Department of NeurologyTaizhou HospitalTaizhouChina
  3. 3.Department of NeurologyFirst People’s Hospital of Linhai CityLinhaiChina
  4. 4.City College of Zhejiang UniversityHangzhouChina

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