title: Intraperitoneal administration of docosahexaenoic acid for 14days increases serum unesterified DHA and seizure latency in the maximal pentylenetetrazol model.
abstract: Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) which has been shown to raise seizure thresholds following acute administration in rats. The aims of the present experiment were the following: 1) to test whether subchronic DHA administration raises seizure threshold in the maximal pentylenetetrazol (PTZ) model 24h following the last injection and 2) to determine whether the increase in seizure threshold is correlated with an increase in serum and/or brain DHA. Animals received daily intraperitoneal (i.p.) injections of 50mg/kg of DHA, DHA ethyl ester (DHA EE), or volume-matched vehicle (albumin/saline) for 14days. On day 15, one subset of animals was seizure tested in the maximal PTZ model (Experiment 1). In a separate (non-seizure tested) subset of animals, blood was collected, and brains were excised following high-energy, head-focused microwave fixation. Lipid analysis was performed on serum and brain (Experiment 2). For data analysis, the DHA and DHA EE groups were combined since they did not differ significantly from each other. In the maximal PTZ model, DHA significantly increased seizure latency by approximately 3-fold as compared to vehicle-injected animals. This increase in seizure latency was associated with an increase in serum unesterified DHA. Total brain DHA and brain unesterified DHA concentrations, however, did not differ significantly in the treatment and control groups. An increase in serum unesterified DHA concentration reflecting increased flux of DHA to the brain appears to explain changes in seizure threshold, independent of changes in brain DHA concentrations.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; University of Toronto Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Marc-Olivier
authors.initials: MO
authors.lastname: Trépanier
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; University of Toronto Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Joonbum
authors.initials: J
authors.lastname: Lim
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; University of Toronto Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Terence K Y
authors.initials: TK
authors.lastname: Lai
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; University of Toronto Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Domenichiello
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Chuck T
authors.initials: CT
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; University of Toronto Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Ameer Y
authors.initials: AY
authors.lastname: Taha
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; University of Toronto Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; University of Toronto Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: mac.burnham@utoronto.ca.
authors.forename: W M
authors.initials: WM
authors.lastname: Burnham
mesh_terms: D000818:Animals; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D004281:Docosahexaenoic Acids; D010433:Pentylenetetrazole
keywords: Docosahexaenoic acid; Omega-3 polyunsaturated fatty acids; Pentylenetetrazol; Rat; Seizures