Anxiolytic effect of exogenous ketone supplementation is abolished by adenosine a1 receptor inhibition in wistar albino glaxo/rijswijk rats

Z. Kovács, Dominic P. D’Agostino, Csilla Ari

Research output: Article

4 Citations (Scopus)

Abstract

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. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A1 receptors (A1 Rs) influence the anxiolytic effect of the exogenous ketone supplement. As A1 Rs may mediate such an effect, in the present study we used a specific A1 R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine) to test whether it modulates the anxiolytic effect of sub-chronically (7 days) applied KSMCT in the previously tested animal model by using elevated plus maze (EPM) test. We administered KSMCT (2.5 g/kg/day) alone by intragastric gavage and in combination with intraperitoneally (i.p.) injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg). Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day). After treatments, the 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. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A1 R inhibition modified (decreased) the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A1 Rs, may modulate the exogenous ketone supplement induced anxiolytic influence.

Original languageEnglish
Article number29
JournalFrontiers in Behavioral Neuroscience
Volume12
DOIs
Publication statusPublished - febr. 22 2018

Fingerprint

Adenosine A1 Receptors
Anti-Anxiety Agents
Ketones
Oils
Triglycerides
Salts
Hydroxybutyrates
Inhibition (Psychology)
Anxiety
3-Hydroxybutyric Acid
Anxiety Disorders
Blood Glucose
1,3-dipropyl-8-cyclopentylxanthine
Mental Health
Animal Models
Body Weight

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Cite this

@article{e1ae447dc9bf4509abe6d4330d6fdc86,
title = "Anxiolytic effect of exogenous ketone supplementation is abolished by adenosine a1 receptor inhibition in wistar albino glaxo/rijswijk rats",
abstract = "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. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A1 receptors (A1 Rs) influence the anxiolytic effect of the exogenous ketone supplement. As A1 Rs may mediate such an effect, in the present study we used a specific A1 R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine) to test whether it modulates the anxiolytic effect of sub-chronically (7 days) applied KSMCT in the previously tested animal model by using elevated plus maze (EPM) test. We administered KSMCT (2.5 g/kg/day) alone by intragastric gavage and in combination with intraperitoneally (i.p.) injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg). Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day). After treatments, the 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. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A1 R inhibition modified (decreased) the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A1 Rs, may modulate the exogenous ketone supplement induced anxiolytic influence.",
keywords = "Adenosine, Anxiety, EPM, Exogenous ketone supplement, Ketosis, WAG/Rij rats",
author = "Z. Kov{\'a}cs and D’Agostino, {Dominic P.} and Csilla Ari",
year = "2018",
month = "2",
day = "22",
doi = "10.3389/fnbeh.2018.00029",
language = "English",
volume = "12",
journal = "Frontiers in Behavioral Neuroscience",
issn = "1662-5153",
publisher = "Frontiers Research Foundation",

}

TY - JOUR

T1 - Anxiolytic effect of exogenous ketone supplementation is abolished by adenosine a1 receptor inhibition in wistar albino glaxo/rijswijk rats

AU - Kovács, Z.

AU - D’Agostino, Dominic P.

AU - Ari, Csilla

PY - 2018/2/22

Y1 - 2018/2/22

N2 - 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. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A1 receptors (A1 Rs) influence the anxiolytic effect of the exogenous ketone supplement. As A1 Rs may mediate such an effect, in the present study we used a specific A1 R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine) to test whether it modulates the anxiolytic effect of sub-chronically (7 days) applied KSMCT in the previously tested animal model by using elevated plus maze (EPM) test. We administered KSMCT (2.5 g/kg/day) alone by intragastric gavage and in combination with intraperitoneally (i.p.) injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg). Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day). After treatments, the 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. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A1 R inhibition modified (decreased) the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A1 Rs, may modulate the exogenous ketone supplement induced anxiolytic influence.

AB - 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. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A1 receptors (A1 Rs) influence the anxiolytic effect of the exogenous ketone supplement. As A1 Rs may mediate such an effect, in the present study we used a specific A1 R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine) to test whether it modulates the anxiolytic effect of sub-chronically (7 days) applied KSMCT in the previously tested animal model by using elevated plus maze (EPM) test. We administered KSMCT (2.5 g/kg/day) alone by intragastric gavage and in combination with intraperitoneally (i.p.) injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg). Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day). After treatments, the 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. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A1 R inhibition modified (decreased) the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A1 Rs, may modulate the exogenous ketone supplement induced anxiolytic influence.

KW - Adenosine

KW - Anxiety

KW - EPM

KW - Exogenous ketone supplement

KW - Ketosis

KW - WAG/Rij rats

UR - http://www.scopus.com/inward/record.url?scp=85043457506&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043457506&partnerID=8YFLogxK

U2 - 10.3389/fnbeh.2018.00029

DO - 10.3389/fnbeh.2018.00029

M3 - Article

AN - SCOPUS:85043457506

VL - 12

JO - Frontiers in Behavioral Neuroscience

JF - Frontiers in Behavioral Neuroscience

SN - 1662-5153

M1 - 29

ER -