title: Pharmacological and neuroethological studies of three antiepileptic drugs in the Genetic Audiogenic Seizure Hamster (GASH:Sal).
abstract: Epilepsy modeling is essential for understanding the basic mechanisms of the epileptic process. The Genetic Audiogenic Seizure Hamster (GASH:Sal) exhibits generalized tonic-clonic seizures of genetic origin in response to sound stimulation and is currently being validated as a reliable model of epilepsy. Here, we performed a pharmacological and neuroethological study using well-known and widely used antiepileptic drugs (AEDs), including phenobarbital (PB), valproic acid (VPA), and levetiracetam (LEV). The intraperitoneal administration of PB (5-20mg/kg) and VPA (100-300mg/kg) produced a dose-dependent decrease in GASH:Sal audiogenic seizure severity scores. The administration of LEV (30-100mg/kg) did not produce a clear effect. Phenobarbital showed a short plasmatic life and had a high antiepileptic effect starting at 10mg/kg that was accompanied by ataxia. Valproic acid acted only at high concentrations and was the AED with the most ataxic effects. Levetiracetam at all doses also produced sedation and ataxia side effects. We conclude that the GASH:Sal is a reliable genetic model of epilepsy suitable to evaluate AEDs.
authors.affiliation: Institute of Neurosciences of Castilla and León/IBSAL, University of Salamanca, Salamanca, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Barrera-Bailón
authors.forename: J A C
authors.initials: JA
authors.lastname: Oliveira
authors.forename: D E
authors.initials: DE
authors.lastname: López
authors.forename: L J
authors.initials: LJ
authors.lastname: Muñoz
authors.forename: N
authors.initials: N
authors.lastname: Garcia-Cairasco
authors.forename: C
authors.initials: C
authors.lastname: Sancho
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020195:Epilepsy, Reflex / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D000077287:Levetiracetam; D008124:Locomotion / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D010634:Phenobarbital / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D010889:Piracetam / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D018398:Homeodomain Proteins; D014157:Transcription Factors; C484468:spalt protein, vertebrate; D000077287:Levetiracetam; D014635:Valproic Acid; D010634:Phenobarbital; D010889:Piracetam
keywords: Animal models of epilepsy; Levetiracetam; Pharmacokinetics; Phenobarbital; Seizures; Valproic acid