title: Brain anticonvulsant protection of mice given chronic carbamazepine under various fatty acid and magnesium diet conditions.
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 (50 mg/kg/day fragmented in two daily intraperitoneal injections of 25 mg/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.
authors: NMPA, CNPS, Paris XI University, Orsay, France.
authors: Nicole
authors: N
authors: Pagès
authors: Pierre
authors: P
authors: Maurois
authors: Bernadette
authors: B
authors: Delplanque
authors: Pierre
authors: P
authors: Bac
authors: Joseph
authors: J
authors: Vamecq
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002220:Carbamazepine / Q000008:administration & dosage* / Q000494:pharmacology; D004032:Diet; D004334:Drug Administration Schedule; D020195:Epilepsy, Reflex / Q000209:etiology / Q000517:prevention & control; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage*; D005260:Female; D008274:Magnesium / Q000008:administration & dosage*; D008275:Magnesium Deficiency / Q000150:complications; D051379:Mice; D016202:N-Methylaspartate; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology; D010672:Phenytoin / Q000008:administration & dosage / Q000494:pharmacology; D012640:Seizures / Q000209:etiology / Q000517:prevention & control; D015398:Signal Transduction
chemical_list: D000927:Anticonvulsants; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D016718:Arachidonic Acid; D002220:Carbamazepine; D010672:Phenytoin; D016202:N-Methylaspartate; D008274:Magnesium; D010634:Phenobarbital