N-methyl-D-aspartate receptor binding is altered and seizure potential reduced in pregnant rats.
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.
Standley
C A
CA
Department of Obstetrics and Gynecology, Wayne State University/Hutzel Hospital, Detroit, MI 48201, USA. cstand@arizona.midwestern.edu
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003292:Convulsants; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011869:Radioligand Assay; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D015763:2-Amino-5-phosphonovalerate; D003292:Convulsants; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D005998:Glycine; D016202:N-Methylaspartate; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C069052:CGP 39653