Neonatal ethanol exposure reduces AMPA but not NMDA receptor levels in the rat neocortex.
Fetal alcohol syndrome (FAS) is the leading cause of mental retardation in western society. We investigated possible changes in glutamate receptor levels in neonatal animals following ethanol exposure using radioligand binding and western blot analysis. We used a vapor chamber to administer ethanol to neonatal Wistar rats 3 h a day from postnatal day (PND) 4-9. A separation control group was separated from their mothers for the same time and duration as the vapor treatment, while a normal control group was left to develop normally. Daily ethanol administrations resulted in decreased brain weight and body weight, as well as microencephaly (decreased brain:body weight ratio). Neither the affinity nor maximum binding of [(3)H]MK-801 (dizoclipine maleate) in the cortex of PND10 rats differed between treatment groups. Western blot analysis also failed to reveal any changes in NMDAR1, NMDAR2A, or NMDAR2B receptor levels. In contrast, the AMPA receptor subunit GluR1 was greatly reduced in vapor-treated pups compared with control pups, as revealed by western blot analysis. A similar reduction was found in westerns with an antibody recognizing the GluR2 and 4 subunits. These results indicate that ethanol reduces AMPA rather than NMDA receptors in the developing neocortex, possibly by blocking NMDA receptors during development.
Bellinger
Frederick P
FP
Alcohol Research Unit, Department of Biochemistry, The University of Queensland, St. Lucia QLD 4072, Australia. rikkugon@yohoo.com
Davidson
Mark S
MS
Bedi
Kuldip S
KS
Wilce
Peter A
PA
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism; D019579:Neocortex / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D014316:Tritium
D000906:Antibodies; D002492:Central Nervous System Depressants; D016291:Dizocilpine Maleate; D000431:Ethanol; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; C104724:glutamate receptor ionotropic, AMPA 4; C104722:glutamate receptor ionotropic, AMPA 2