title: Role of the adenosine system and glucose restriction in the acute anticonvulsant effect of caprylic acid in the 6 Hz psychomotor seizure test in mice.
abstract: Although several studies have reported the acute anticonvulsant activity of caprylic acid in animal seizure models, little is known about the mechanism underlying this effect. Recently, the role of adenosine in the efficacy of the ketogenic diet has been postulated. Therefore, the present study aimed to evaluate the possible involvement of the adenosine system (in non-fasted mice) as well as the role of glucose restriction (in fasted and non-fasted mice) in the acute anticonvulsant activity of caprylic acid in the 6 Hz psychomotor seizure threshold test. We showed that the anticonvulsant effect of caprylic acid (30 mmol/kg, p.o.) was reversed by a selective adenosine A1 receptor antagonist (DPCPX, 1mg/kg, i.p.) and a selective adenosine A2A receptor antagonist (KW-6002, 1 mg/kg, p.o.) but not by glibenclamide (1 pg/mouse, i.c.v.) - the ATP-sensitive potassium (KATP) channel blocker. Co-administration of an ineffective dose of caprylic acid (20 mmol/kg) with an ineffective dose of adenosine transporter inhibitor (dipyridamole, 50 mg/kg, i.p.) significantly raised the threshold for the 6 Hz-induced seizures. A high dose of glucose (2 g/kg) significantly only diminished the anticonvulsant effect of caprylic acid (30 mmol/kg) in non-fasted mice, and this was accompanied by an increase in blood glucose level and no changes in ketone body level as compared to the caprylic acid-treated group. In both fasted and non-fasted mice treated with glucose and caprylic acid, a significant decrease in trunk blood pH occurred as compared to the control group. No alternations in motor coordination or muscular strength were noted with any drug treatment, apart from the caprylic acid and glibenclamide combination, where a significant decrease in the muscle strength was observed. The present study provides a new insight into the role of the adenosine system and low glucose usage in the mechanisms underlying the anticonvulsant effects of caprylic acid in the 6 Hz seizure test.
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland. Electronic address: ksocala@op.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Socała
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Nieoczym
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Pieróg
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wlaź
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000241:Adenosine / Q000378:metabolism*; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D002210:Caprylates / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005215:Fasting; D005947:Glucose / Q000172:deficiency*; D005905:Glyburide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D009048:Motor Skills / Q000187:drug effects*; D053580:Muscle Strength / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D012640:Seizures / Q000097:blood / Q000188:drug therapy*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000927:Anticonvulsants; D001786:Blood Glucose; D002210:Caprylates; D007004:Hypoglycemic Agents; D010726:Phosphodiesterase Inhibitors; D011687:Purines; D014970:Xanthines; C111599:istradefylline; D004176:Dipyridamole; C051360:1,3-dipropyl-8-cyclopentylxanthine; D005947:Glucose; D000241:Adenosine; C031492:octanoic acid; D005905:Glyburide; D020155:3-Hydroxybutyric Acid
keywords: 6Hz seizure test; Adenosine; Caprylic acid; Mice