Role of dopamine D3 receptor in alleviating behavioural deficits in animal models of post-traumatic stress disorder.

Abstract

Post-traumatic stress disorder (PTSD) is a complicated psychiatric disorder, which occurs after exposure to a traumatic event. The main clinical manifestation of PTSD includes fear and stress dysregulation. In both animals and humans, dysregulation of dopamine function appears to be related to conditioned fear responses. Previous studies show that the dopamine D3 receptor (D3R) is involved in schizophrenia, autism, and substance use disorders and is related to emotional disorders. However, few studies have investigated the role of the D3R in the pathogenesis and aetiology of PTSD. In the current study, we have reported that D3R knockout (D3R-/-) mice displayed decreased freezing time of contextual fearing and anxiolytic effects following training sessions consisting of exposure to inescapable electric foot-shocks. Similarly, highly selective blockade of D3Rs by YQA14, a novel D3R antagonist, significantly ameliorated freezing and anxiogenic-like behaviours in the single-prolonged stress (SPS) model of PTSD in rats. And more, YQA14 selectively alleviated the symptoms of PTSD in WT mice but not in D3R-/- mice. In summary, this study demonstrates the anti-PTSD effects of blockade or knockout of the D3R, suggesting that the D3R might play an important role in the pathogenesis and aetiology of PTSD, and might be a potential target for the clinical management of PTSD.

• Authors: Dake Song, Yaping Ge, Zhaodi Chen, Chao Shang, Ying Guo, Taiyun Zhao, Yunfeng Li, Ning Wu, Rui Song, Jin Li
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 84 Issue Pt A Pg. 190-200 (06 08 2018) ISSN: 1878-4216 [Electronic] England
• PMID: 29510167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• Benzoxazoles
• Dopamine Antagonists
• Piperazines
• Receptors, Dopamine D3
• YQA14

Topics

• Animals
• Anxiety (drug therapy, metabolism)
• Benzoxazoles (pharmacology)
• Disease Models, Animal
• Dopamine Antagonists (pharmacology)
• Electroshock
• Freezing Reaction, Cataleptic (drug effects, physiology)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Piperazines (pharmacology)
• Rats, Sprague-Dawley
• Receptors, Dopamine D3 (antagonists & inhibitors, genetics, metabolism)
• Stress Disorders, Post-Traumatic (drug therapy, metabolism)