Amygdala-kindled and pentylenetetrazole-induced seizures in glutamate transporter GLAST-deficient mice

The glutamatergic system has been shown to be important for the induction o f epileptiform activity and the development of epileptogenesis. To investig ate the role of the astroglial glutamate transporter GLAST in epileptogenes is, we examined amygdala (AM)-kindled and pentylenetetrazole (PTZ)-induced seizures in GLAST-deficient mice (GLAST(-/-)) and compared them to those ob served in wild-type mice (GLAST(+/+) and maternal C57Black6/J(C57) mice. AM -kindling resulted in no significant differences in afterdischarge threshol d or in the seizure responses induced by first stimulation between these gr oups. In addition, although no significant differences were seen in kindled seizure development, the generalized seizure duration of AM-kindled seizur es in GLAST(-/-) mice was significantly prolonged (approximately 35%) compa red with that of C57 mice. Furthermore, GLAST(-/-) mice showed more severe stages of PTZ-induced seizures than GLAST(+/+) mice, and the latency to the onset of seizures was significantly shorter for the mutant mice. These res ults indicate that GLAST is one of factors determinig seizure susceptibilit y. (C) 1999 Elsevier Science B.V. All rights reserved.