Acute administration of docosahexaenoic acid increases resistance to pentylenetetrazol-induced seizures in rats.
OBJECTIVE
Docosahexaenoic acid (DHA), an omega-3 fatty acid, has been reported to raise seizure thresholds. The purpose of the present study was to test the acute anticonvulsant effects of unesterified DHA in rats, using the maximal pentylenetetrazol (PTZ) seizure model, and also to examine DHA incorporation and distribution into blood serum total lipids and brain phospholipids and unesterified fatty acids. Sedation was measured to monitor for the potential toxicity of DHA.


METHODS
Male Wistar rats received subcutaneous injections of saline, oleic acid (OA), or DHA. An initial pilot study (Experiment 1) established 400mg/kg as an effective dose of DHA in the maximal PTZ seizure test. A subsequent time-response study, using 400mg/kg (Experiment 2), established 1 hour as an effective postinjection interval for administering DHA subcutaneously. A final study (Experiment 3) comprised two different groups. The first group ("seizure-tested rats") received saline, OA, or DHA (400mg/kg) subcutaneously, and were seizure tested in the maximal PTZ test 1 hour later to confirm the seizure latency measurements at that time. The second group ("assay rats") received identical subcutaneous injections of saline, OA, or DHA (400mg/kg). One hour postinjection, however, they were sacrificed for assay rather than being seizure tested. Assays involved the analysis of serum and brain DHA. Sedation was measured in both Experiment 3 groups during the 1-hour period prior to seizure testing or sacrifice.


RESULTS
As noted above, 400mg/kg proved to be an effective subcutaneous dose of DHA (Experiment 1), and 1 hour proved to be the most effective injection-test interval (Experiment 2). In Experiment 3, in the seizure-tested animals, subcutaneous administration of 400mg/kg of DHA significantly increased latency to PTZ seizure onset 1 hour postinjection relative to the saline- and OA-injected controls, which did not differ significantly from each other (P>0.05). In the assay animals, no significant effects of treatment on blood serum total lipids or on brain phospholipid or unesterified fatty acid profiles (P>0.05) were observed. There were also no differences in sedation among the three groups (P>0.05).


CONCLUSIONS
DHA increases resistance to PTZ-induced seizures without altering measures of sedation and, apparently, without changing DHA concentrations in serum or brain.
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. a.taha@utoronto.ca
Ameer Y
AY
Taha
Melanie A
MA
Jeffrey
Nadeen M Y
NM
Taha
Saimir
S
Bala
W M
WM
Burnham
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D007279:Injections, Subcutaneous / Q000379:methods; D008055:Lipids / Q000097:blood; D008297:Male; D019301:Oleic Acid / Q000494:pharmacology / Q000627:therapeutic use; D010433:Pentylenetetrazole; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors
D000927:Anticonvulsants; D005227:Fatty Acids; D008055:Lipids; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D010433:Pentylenetetrazole