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 (A1Rs) influence the anxiolytic effect of the exogenous ketone supplement. As A1Rs may mediate such an effect, in the present study we used a specific A1R 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 A1R inhibition modified (decreased) the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A1Rs, may modulate the exogenous ketone supplement induced anxiolytic influence.
Highlights
Anxiety disorders, such as panic disorder, post-traumatic stress disorder, and specific phobias, are one of the most common mental health problems worldwide, which disorders may be associated with impairment of quality of life (Li, 2012)
Consistent with our previous study (Ari et al, 2016), after 7 days of oral gavage, ketone salt/KS + medium chain triglyceride/medium chain triglyceride (MCT) (KSMCT) (2.5 g/kg/day) significantly increased the time spent in the open arms (p < 0.0001), whereas decreased the time spent in the closed arms (p
In this study we demonstrated that inhibition of adenosine A1 receptor (A1R) by i.p
Summary
Anxiety disorders, such as panic disorder, post-traumatic stress disorder, and specific phobias, are one of the most common mental health problems worldwide, which disorders may be associated with impairment of quality of life (Li, 2012). Our knowledge about the exact cause and pathomechanism of anxiety disorders is far from complete. It has been demonstrated that mainly glutamatergic, serotoninergic, GABAergic and, based on recent results, adenosinergic systems as well as different brain structures (e.g., amygdala and hippocampus) contribute to the pathophysiology of anxiety (Kakui et al, 2009; Masino et al, 2009; Li, 2012; Dias et al, 2013). The exact role of adenosinergic system in the pathomechanism of anxiety is poorly understood, it has been previously suggested that adenosine may reduce anxiety (Jain et al, 1995; Johansson et al, 2001; Masino et al, 2009, 2012), which approach may lead to a new therapeutic approach
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