title: A once-per-day, drug-in-food protocol for prolonged administration of antiepileptic drugs in animal models.
abstract: OBJECTIVE
  Convenient and effective methods for administering potential antiepileptic drugs (AEDs) chronically should facilitate many experiments in animal models of chronic epilepsy with spontaneous recurrent seizures. This proof-of-principle study aimed to optimize a once-per-day, drug-in-food protocol by testing the effect of carbamazepine (CBZ) on the frequency of convulsive seizures in rats with kainate-induced epilepsy.
  
  
  METHODS
  Adult male rats were given repeated low-dose kainate injections until convulsive status epilepticus persisted for >3 h. After the rats developed spontaneous recurrent seizures, food pellets with CBZ (30, 100, or 300 mg/kg/day) were provided once per day in three 2-week trials (n = 7-9 rats) involving 5 days of CBZ or control treatment, separated by two recovery days within a trial. The total amount of food provided and consumed per day corresponded to a normal caloric diet (60 g/kg/day).
  
  
  RESULTS
  When provided once per day, all animals ate the CBZ-containing food irregularly but continuously throughout the 24-h day. With this daily feeding protocol, CBZ significantly reduced the frequency of spontaneous convulsive seizures in a dose-dependent manner. It is important to note that the effect of CBZ was consistent across the 5 days and throughout each day of the trials. With food administered at 9:00 a.m., and blood assayed at 5:00 p.m., higher food levels of CBZ resulted in higher plasma concentrations of CBZ.
  
  
  CONCLUSIONS
  This AED-in-food protocol is simple, efficient, inexpensive, reliable, and noninvasive; it allows easier long-term drug administration and is less stressful and more humane than other methods of AED administration.
authors.affiliation: Department of Physiology, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA.
authors.forename: Atif
authors.initials: A
authors.lastname: Ali
authors.forename: Yashomati
authors.initials: Y
authors.lastname: Dua
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Constance
authors.forename: Michael R
authors.initials: MR
authors.lastname: Franklin
authors.forename: F Edward
authors.initials: FE
authors.lastname: Dudek
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology*; D002220:Carbamazepine / Q000008:administration & dosage* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy; D005526:Food, Formulated; D007608:Kainic Acid; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D051381:Rats; D012640:Seizures / Q000188:drug therapy*; D013226:Status Epilepticus / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D004364:Pharmaceutical Preparations; D002220:Carbamazepine; D007608:Kainic Acid