Beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, attenuates anxiety-related behavior in a rodent post-traumatic stress disorder model

Sci Rep. 2020 Dec 10;10(1):21629. doi: 10.1038/s41598-020-78410-2.


Accumulating evidence suggests that elevated inflammation contributes to the pathophysiology of post-traumatic stress disorder (PTSD) and that anti-inflammatory drugs might be a new treatment strategy for PTSD. It has been reported that beta-hydroxybutyrate (BHB), one of the main ketone bodies produced, can have an anti-inflammatory and antidepressant effect. Here, we investigated the potential anti-anxiety and anti-inflammatory effects of BHB using a rodent PTSD model, induced by single prolonged stress (SPS). Male, Sprague-Dawley rats were employed in this study. Repeated administration of BHB attenuated SPS-induced anxiety-related behaviors evaluated by the elevated plus maze test. SPS increased the serum levels of TNF-α and IL-1β. In contrast, BHB administration partially attenuated the increase of serum TNF-α. These findings demonstrate that BHB exerts its anxiolytic effects, possibly by inhibiting systemic TNF-α. Hence, BHB may be a novel therapeutic candidate for the treatment of PTSD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / administration & dosage*
  • 3-Hydroxybutyric Acid / blood
  • Animals
  • Anxiety / etiology
  • Anxiety / prevention & control*
  • Disease Models, Animal
  • Inflammasomes / antagonists & inhibitors*
  • Injections, Subcutaneous
  • Male
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Stress Disorders, Post-Traumatic / complications*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • Tumor Necrosis Factor-alpha
  • 3-Hydroxybutyric Acid