What is it about?
https://doi.org/10.3389/fnbeh.2018.00029 Anxiety disorders are one of the most common mental health problems worldwide, but the exact pathophysiology remains largely unknown. It has been demonstrated previously that administration of exogenous ketone supplement KSMCT (ketone salt/KS + medium chain triglyceride/MCT oil) by intragastric gavage for 7 days decreased the anxiety level in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. Although the exact role of adenosinergic system in the pathomechanism of anxiety is poorly understood, it was revealed that adenosinergic system may modulate anxiety-like behavior and blockade of adenosine A1 receptors (A1Rs) may have a role in the influence of exogenous ketone supplements on CNS diseases. As A1Rs may mediate the effect of ketone supplements on level of anxiety, which effect could lead to a new promising therapeutic approach, we addressed in the present study whether inhibition of A1Rs by its specific antagonist DPCPX (1,3-dipropyl-8-cyclopentylxanthine) can modulate the effect of sub-chronically (for 7 days) applied KSMCT on anxiety-like behavior in WAG/Rij rats. To investigate anxiety level of animals we used elevated plus maze (EPM) test. We applied KSMCT (2.5 g/kg/day) alone by intragastric gavage and in combination with intraperitoneally (i.p.) injected two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg) of DPCPX. After different treatments, level of blood glucose and beta-hydroxybutyrate (βHB), as well as body weight were recorded. KSMCT alone significantly increased the time spent in the open arms and decreased the time spent in the closed arms, supporting our previous results. Moreover, KSMCT administration resulted in more entries to open and less entries to closed arms. Injection of lower dose of DPCPX decreased, whereas higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after application of KSMCT, while DPCPX did not change the KSMCT gavage-evoked increase in blood βHB levels.
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Why is it important?
A1R blockade modified (decreased) the anti-anxiety effect of KSMCT administration suggesting that the adenosinergic system, likely via A1Rs, may modulate the exogenous ketone supplements-evoked anxiolytic influence.
Perspectives
We can conclude that administration of exogenous ketone supplement KSMCT may be a potential therapeutic approach in the treatment of therapy-resistant types of anxiety disorders. Strict dietary restrictions for example by classical ketogenic diets also evoke nutritional ketosis but rigorous procedures of these diets are difficult to follow and compliance is questionable. Nevertheless, inducing nutritional ketosis by exogenous ketogenic supplements allow for a rapid and sustained dietary ketosis independent of dietary restriction (normal diet + supplement). Thus, achieving nutritional ketosis by means of exogenous ketone supplementation might be an alternative method not only to the ketogenic diet but also to reduce symptoms of different CNS diseases such as anxiety.
Dr Zsolt Kovacs
Eötvös Loránd University
Read the Original
This page is a summary of: Anxiolytic Effect of Exogenous Ketone Supplementation Is Abolished by Adenosine A1 Receptor Inhibition in Wistar Albino Glaxo/Rijswijk Rats, Frontiers in Behavioral Neuroscience, February 2018, Frontiers,
DOI: 10.3389/fnbeh.2018.00029.
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