The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: behavior and metabolism.
This work describes a novel epilepsy model, combining pentylenetetrazole (PTZ) kindling with the senescence-accelerated mouse P8 (SAMP8) a model for aging. The 2- and 8-month-old SAMP8 mice were treated with PTZ, phenobarbital plus PTZ or saline every 48 h during a period of 40 days. Both 2- and 8-month-old PTZ-kindled mice showed a behavioral pattern that was very similar to severe chronic epilepsy with secondary generalized seizures. Two out of six 8-month-old animals died in the PTZ group. Interestingly, atypical absence seizures were limited to the 8-month-old PTZ group. Furthermore, 8-month-old mice were more sensitive to the sedative effect of phenobarbital. The concentrations of several amino acids were examined by HPLC. Lower levels of amino acids were found in the 8-month-old compared to the 2-month-old control animals. No biochemical changes were observed between the groups of 2-month-old animals, while in the 8-month-old animals both treatment groups showed significantly higher concentrations of GABA, glutamine and glutathione. Thus, it could be shown that cerebral metabolism of 8-month-old SAMP8 mice was more sensitive to PTZ and phenobarbital than metabolism of 2-month-old mice. Furthermore, it is suggested that glutamate metabolism in brains of 8-month-old SAMP8 mice is altered and that excessive glutamate is transformed, in considerable amounts, into glutamate related metabolites, possibly in astrocytes.
Kondziella
Daniel
D
Department of Clinical Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
Bidar
Abdel
A
Urfjell
Bente
B
Sletvold
Olav
O
Sonnewald
Ursula
U
D000375:Aging / Q000502:physiology*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism* / Q000523:psychology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007696:Kindling, Neurologic; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D013997:Time Factors
D000596:Amino Acids; D000927:Anticonvulsants; D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D006993:Hypnotics and Sedatives; D010433:Pentylenetetrazole; D010634:Phenobarbital