The role of
glutamate receptors in the inferior colliculus (IC) in audiogenic and audiogenic-like
seizures was investigated in adult rats with transient neonatal
hypothyroidism by 0.02%
propylthiouracil (PTU) treatment through mother's milk (PTU rats) and in naive rats treated intracisternally with
N-methyl-d-aspartate (
NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic
acid (
AMPA), or
cyclothiazide, an inhibitor of rapid
AMPA receptor desensitization. All rats showed audiogenic or audiogenic-like
seizures characterized by running fit (RF) and
generalized tonic-clonic seizures (GTCS). While systemically administered
MK-801 inhibited GTCS, intracisternally administered
NBQX inhibited RF and GTCS in both audiogenic and audiogenic-like
seizures. Auditory stimulation shortened the latency to GTCS induced by
AMPA, but not
NMDA, at a subclinical dose and further elongated the shortened duration of RF, but not GTCS, induced by
MK-801 pretreatment. Furthermore, Northern blot analysis was used to evaluate the expression of the immediate-early gene c-fos in the IC following induction of audiogenic or audiogenic-like
seizures. The significant induction of c-fos
mRNA by audiogenic
seizures in PTU rats or by
AMPA- or
cyclothiazide-induced
seizures in naive rats was prominent in the IC.
MK-801 suppressed c-fos
mRNA expression in the IC induced by audiogenic
seizures in PTU rats or by
AMPA-induced
seizures in naive rats.
NBQX suppressed the expression of c-fos
mRNA in the IC induced by
AMPA-induced
seizures but did not suppress c-fos
mRNA in PTU rats or rats with
cyclothiazide-induced
seizures. Auditory stimuli failed to affect c-fos
mRNA induction by
AMPA. The present study suggests that audiogenic-like
seizures can be reproduced by
glutamate receptor agonists in which
AMPA receptors are primarily linked to the initiation of audiogenic
seizures (RF) while
NMDA receptors presumably located within the IC are involved in the propagation of GTCS in audiogenic
seizures.