Seizures have been shown to promote the proliferation of granule cell precursors in the adult brain, but the underlying mechanisms remain largely unknown. Using systemic
bromodeoxyuridine (
BrdU) to label dividing cells, we examined the effects of selective
ionotropic glutamate receptor antagonists on granule cell precursor proliferation in adult rats after pentylenetrazol (PTZ)-induced generalized
clonic seizures. We found that the
NMDA receptor antagonist
MK-801 significantly inhibited behavioral and EEG
seizures and completely blocked seizure-induced increase in the number of
BrdU-labeled cells in the dentate gyrus. Although the
AMPA/KA receptor antagonist
DNQX was not observed to affect
seizures, it significantly suppressed the number of
BrdU-labeled cells in the dentate gyrus. Double immunohistochemical staining showed that both the mature granule cells and the majority of
BrdU-labeled, mitotically active cells expressed the
NMDA receptor subunit NR1 and the
AMPA/KA receptor subunit GluR2. Because accumulated evidence showed that mild
seizures are sufficient to promote precursor cell proliferation, the present findings that
MK-801 inhibited
seizures and completely blocked seizure-induced increase in precursor cell proliferation suggest that the direct blockade action of
MK-801 on
NMDA receptors on the granule cell precursors may play an important role in blocking seizure-induced precursor cell proliferation. The suppression of seizure-induced proliferation of granule cell precursors by
DNQX may be achieved by the direct action of
DNQX on
AMPA/KA receptors on the granule cell precursors. Thus, our findings indicate that
seizures may promote cell proliferation in the adult rat dentate gyrus through glutamatergic mechanisms acting on both
NMDA and
AMPA/KA receptors.