The objective of this study was to determine if a change in brain tissue
excitatory amino acid receptor binding occurs during pregnancy using in vitro quantitative autoradiography and to examine seizure potential during pregnancy via central injection of
N-methyl-D-aspartate (
NMDA). For the receptor autoradiography studies, eight pregnant rats (day 21) and eight non-pregnant rats were euthanized with
carbon dioxide, perfused, their brains dissected and frozen. Cryostat sections were taken and labeled in vitro by one of the following
ligands: [3H]-
CGP 39653, [3H]-
glycine, [3H]-
MK-801, [3H]-2-amino-3-hydroxy-5-methyl-4-
isoxazole propionate (
AMPA) or [3H]-
kainate. Optical density measurements of binding in 11 brain regions were performed using image analysis. To test seizure susceptibility, 74 rats were surgically implanted with an
electrode into the hippocampus and a
cannula into the lateral ventricle. Rats were mated; others served as non-pregnant controls. On gestational day 20, rats were randomized to receive no
drug or an injection of
NMDA (34, 68 or 136 nmol) through their indwelling
cannulae.
Seizures were assessed for 20 min. During pregnancy, the density of the
NMDA competitive antagonist site measured by [3H]-
CGP 39653 was decreased in the hippocampus, thalamus and hypothalamus (P<0.01), while the
glycine modulation site was decreased in the cortex, hippocampus, thalamus, caudate and cerebellum (P<0.01).
Kainate binding was significantly decreased in the hippocampus (P<0. 05). Total seizure duration and total number of
seizures were significantly reduced in pregnant vs. non-pregnant rats (P<0.05). Pregnancy is associated with a significant alteration of
NMDA and non-
NMDA receptor binding in rats. These findings suggest that pregnancy affords some protection against
seizures induced by an activation of
NMDA receptors in the brain.