Dose-dependent anticonvulsant effects of linoleic and alpha-linolenic polyunsaturated fatty acids on pentylenetetrazol induced seizures in rats.
OBJECTIVE
Linoleic and alpha-linolenic polyunsaturated fatty acids, derived from plant oils, have been reported to reduce neuronal excitability ex vivo and in cell culture. The evidence derived from animal seizure models, however, has been contradictory. The goal of the present study was to assess the dose-dependent anticonvulsant effects of a fatty acid mixture containing linoleic and alpha-linolenic acids in a 4 to 1 ratio (the "SR-3" compound).


METHODS
The maximal pentylenetetrazol seizure model and Long-Evans hooded rats were used.


RESULTS
Daily intraperitoneal injection of SR-3 for 21 consecutive days raised omega-3 polyunsaturated fatty acid (n-3 PUFA) composition in the unesterified fatty acid fraction of brain lipids (p < 0.05), and increased latency to seizure onset when administered at 200 mg/kg (p < 0.05), but not at 40 mg/kg (p > 0.05). There were no significant effects of SR-3 on seizure occurrence or on seizure severity (p > 0.05). A toxic effect of the SR-3 compound on peristalsis was observed at a dose of 400 mg/kg and above.


CONCLUSIONS
Linoleic and alpha-linolenic polyunsaturated fatty acids in a 4 to 1 ratio raises n-3 PUFA composition of unesterified fatty acids in the brain and increases resistance to pentylenetetrazol-induced seizures.
Taha
Ameer Y
AY
Department of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Canada. a.taha@utoronto.ca
Filo
Elvis
E
Ma
David W L
DW
McIntyre Burnham
W
W
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D003292:Convulsants / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019787:Linoleic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012640:Seizures / Q000139:chemically induced*; D017962:alpha-Linolenic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000927:Anticonvulsants; D003292:Convulsants; D017962:alpha-Linolenic Acid; D019787:Linoleic Acid; D010433:Pentylenetetrazole