Effects of chronic prenatal ethanol exposure on NMDA receptor number and affinity for [3H]MK-801 in the cerebral cortex of the young postnatal and adult guinea-pig
Rajan K. Puri A , James N. Reynolds A and James F. Brien A B
+ Author Affiliations
- Author Affiliations
A Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen’s University, Kingston, Ontario, K7L 3N6, Canada.
B Author to whom correspondence should be addressed. email: brienj@post.queensu.ca
Reproduction, Fertility and Development 15(4) 207-214 https://doi.org/10.1071/RD03022
Submitted: 4 March 2003 Accepted: 1 May 2003 Published: 13 August 2003
Abstract
The objective of this study was to test the hypothesis that chronic prenatal ethanol exposure (CPEE) produces changes in the number and/or affinity of N-methyl-D-aspartate (NMDA) receptors in the cerebral cortex that are developmental-age-dependent. Timed, pregnant Dunkin–Hartley-strain guinea-pigs received oral intubation of one of the following regimens, given daily as two equally divided doses 2 h apart, from gestational day (GD) 2 to GD 67 (term, ∼GD 68): (i) 4 g ethanol kg−1 maternal bodyweight; (ii) isocaloric sucrose with pair feeding; or (iii) water. Maternal blood ethanol concentration was measured on GD 57 or 58 at 1 h after the daily dose, and was 51.1 ± 8.5 mM (235 ± 39 mg dL−1; n = 8). At postnatal day (PD) 11 (pre-weaning) and PD 61 (adulthood), body, brain and cerebral cortical weights of the offspring were measured. The number of NMDA receptors and their affinity for [3H]MK-801 were measured in a crude cerebral cortical membrane preparation using saturation isotherm analysis to determine the Bmax and KD. Chronic prenatal ethanol exposure decreased offspring brain and cerebral cortical weights at PD 11 and PD 61. At PD 11, there was no CPEE-induced change of [3H]MK-801 binding characteristics in the cerebral cortex. At PD 61, both Bmax and KD for [3H]MK-801 binding to cerebral cortical NMDA receptors were decreased by CPEE compared with the isocaloric sucrose/pair-fed and water treatment groups. Loss of cerebral cortical NMDA receptors and increased affinity of the remaining receptors for [3H]MK-801 in the adult guinea-pig, compared with no change in the number or affinity of these receptors in the young postnatal offspring, demonstrated that the effects of CPEE on these ionotropic glutamate receptors are developmental-age-dependent.
Extra keywords: ethanol central nervous system teratogenicity
Acknowledgments
This research was supported by an operating grant from the Canadian Institutes of Health Research (MT-8073).
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