Serotonin 5-HT1A receptors modulate depression-related symptoms following mild traumatic brain injury in male adult mice

  • Morteza Kosari-Nasab
  • Ghaffar Shokouhi
  • Maryam Azarfarin
  • Maryam Bannazadeh Amirkhiz
  • Mehran Mesgari Abbasi
  • Ali-Akbar SalariEmail author
Original Article


Traumatic brain injury is a complex phenomenon leading to neurological diseases and persistent disability that currently affects millions of people worldwide. Increasing evidence shows that a wide range of patients with mild traumatic brain injury (mTBI) suffer from depression during the initial stages of injury and the post-acute stages of recovery. However, the underlying mechanisms involved in depression following mTBI are still not fully understood. The aim of this study was to determine whether serotonin 5-hydroxytryptamine-1A (5-HT1A) receptor is involved in the regulation of depression-related behaviors following mild traumatic brain injury in mice. Mice with or without mTBI received intracerebroventricular injections of 5-HT1A receptor agonist (8-OH-DPAT) or antagonist (WAY-100635) for 5 days, then animals were subjected to behavioral tests. Four behavioral tests including novelty-suppressed feeding test, forced swim test, sucrose preference test and tail suspension test were used to evaluate depression-related symptoms in animals. Our results indicated that mTBI induction increased depression-like symptoms through altering serotonin 5-HT1A receptor activity in the brain. Activation of 5-HT1A receptor by a subthreshold dose of 8-OH-DPAT led to a significant decrease in depression-like behaviors, whereas blockade of 5-HT1A receptor by a subthreshold dose of WAY-100635 resulted in a considerable increase in depression-like phenotypes in mTBI-induced mice. The major strength of the present study is that depression-related symptoms were assessed in four behavioral tests. The present study supports the idea that disturbances in the function of serotonergic system in the brain following mTBI can play an important role in the regulation of depression-related behaviors.


SSRIs Brain injury Serotonin 5-HT1A Depression Mice 



Traumatic brain injury


Mild traumatic brain injury


Selective serotonin reuptake inhibitors




Artificial cerebral spinal fluid


mean + standard error of the mean


Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran
  2. 2.Department of NeurosurgeryTabriz University of Medical SciencesTabrizIran
  3. 3.Neuroscience Research CenterTabriz University of Medical SciencesTabrizIran
  4. 4.Higher Education Institute of Rab – RashidTabrizIran
  5. 5.Salari Institute of Cognitive and Behavioral Disorders (SICBD)AlborzIran

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