Prostaglandins Leukot Essent Fatty Acids. 2012 Jun 30. [Epub ahead of print]

Brain anticonvulsant protection of mice given chronic carbamazepine under various fatty acid and magnesium diet conditions.

Pagès N, Maurois P, Delplanque B, Bac P, Vamecq J.

NMPA, CNPS, Paris XI University, Orsay, France; Toxicology, Pharmacy, Strasbourg University, Illkirch, France.

Abstract

The anticonvulsant and mood stabilizer drug carbamazepine (CBZ) was evaluated for anti-seizure activity after drug pretreatment of young weaning mice given various oil-based diets. These diets had various mono-(MUFA) and poly-(PUFA) unsaturated fatty acid contents, were associated or not with magnesium deprivation, and were given over the entire experimental period (34 days). The diets included a commercial and three purified synthetic diets (n-6 PUFA, n-3 PUFA and MUFA-based chows containing 5% corn/sunflower oils 1:3, 5% rapeseed oil and 5% high oleic acid sunflower oil/sunflower oil 7:3, respectively). A 10-days CBZ treatment (50mg/kg/day fragmented in two daily intraperitoneal injections of 25mg/kg) was given 20 days after initiating diet administration and evaluations of mice was performed 4 days after arrest of CBZ in various seizure tests. In these conditions, CBZ pretreatment still exhibited anticonvulsant protection especially in magnesium-deficient animals. Ethosuximide (ESM)-like profiles under MUFA and n-3 PUFA diets and unusual GABA(A)ergic profile under n-6 PUFA diet in magnesium-deficiency dependent audiogenic seizures (MDDAS) test as well as protection against NMDA-induced seizures in all lipid (n-3 PUFA>MUFA and n-6 PUFA) diet conditions were observed in CBZ-pretreated mice. By highlighting ESM-like and anti-NMDA mechanisms previously induced by an n-3 PUFA diet, present CBZ anticonvulsant properties suggest brain protective targets common to CBZ and n-3 PUFAs.

PMID:22749692