Amino acid levels in some lethargic mouse brain areas before and after pentylenetetrazole kindling

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2005-05, Vol.81 (1), p.47-53
• Main Authors: De Luca, Grazia, Di Giorgio, Rosa Maria, Macaione, Salvatore, Calpona, Pina Rita, Costantino, Santa, Di Paola, Eugenio Donato, Costa, Nicola, Rotiroti, Domenicantonio, Ibbadu, Guido Ferreri, Russo, Emilio, De Sarro, Giovambattista
• Format: Article
• Language: English
• Subjects: Absence seizures; Amino Acids - metabolism; Animals; Biochemistry and metabolism; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Central nervous system; Epilepsy; Fundamental and applied biological sciences. Psychology; Kindling, Neurologic - drug effects; Kindling, Neurologic - metabolism; Lethargic mice; Male; Mice; Mice, Knockout; Neuroactive amino acids; Pentylenetetrazole - toxicity; Pentylenetetrazole kindling; Seizures - chemically induced; Seizures - metabolism; Sleep Stages - drug effects; Sleep Stages - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2005.02.012

Genetic animal models have contributed significantly to our understanding of epilepsy causes. Lethargic mice are considered a valid model of absence epilepsy, which have been shown to possess behavioral, electrographic and pharmacological profiles similar to those of humans with absence epilepsies. Single gene mutations that comprise the β 4 subunit of voltage-sensitive Ca 2+ channels underlie the spontaneous discharges of the absence, non-convulsive seizures of lethargic mice. There are no available data concerning how the mutant channels actually behave at terminals in response to chemical activation by subconvulsant stimulation with pentylenetetrazole. In this study, we found no significant difference in the convulsive dose 50 between lethargic and control mice. Lethargic mice showed a more rapid development of kindling to pentylenetetrazole than control animals. No significant differences were observed between the groups of mice rechallenged with pentylenetetrazole 30 or 60 days after the end of the chronic treatment. Marked differences in brain amino acid levels were found between the two strains of mice in basal conditions and after kindling. In conclusion, our results indicate that lethargic mice show a range of biochemical and behavioral changes, correlated in particular with a higher susceptibility to develop kindled seizures.