Chronic prenatal ethanol exposure alters ionotropic glutamate receptor subunit protein levels in the adult guinea pig cerebral cortex.
BACKGROUND
The superfamily of glutamate-gated ion channels mediates fast excitatory synaptic transmission in the central nervous system and is composed of the NMDA, AMPA, and kainate receptors. Binding studies have shown that chronic prenatal and/or neonatal ethanol exposure produces persistent effects on the numbers of some of these channels. However, whether or not this chronic ethanol exposure produces long-lasting effects on the expression of specific ionotropic receptor subunits remains an open question.


METHODS
Timed pregnant Dunkin-Hartley strain guinea pigs received oral administration of one of the following regimens between gestational days 2 and 67: (1) 4 g of ethanol per kilogram of maternal body weight per day with ad libitum access to pellet food and water (ethanol group), (2) isocaloric sucrose- and pair-feeding with ad libitum access to water (sucrose group), or (3) isovolumetric water with ad libitum access to food and water (water group). The maternal blood ethanol concentration produced by the ethanol regimen was 71 +/- 12 mM. Adult offspring were killed on postnatal day 61, and cerebral cortical tissue was analyzed for ionotropic glutamate receptor subunit expression by Western immunoblotting.


RESULTS
There was a statistically significant decrease in NR2B subunit protein expression and an increase in GluR2/3 subunit protein expression in the ethanol group. Expression of NR1, NR2A, NR2C, GluR1, GluR6/7, and KA2 subunit proteins was not affected.


CONCLUSIONS
These results demonstrate that chronic prenatal ethanol exposure produces long-lasting effects on the subunit composition of NMDA and AMPA receptors in the cerebral cortex of the adult guinea pig.
Dettmer
Todd S
TS
Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque 87131-0001, USA.
Barnes
Alicia
A
Iqbal
Umar
U
Bailey
Craig D C
CD
Reynolds
James N
JN
Brien
James F
JF
Valenzuela
C Fernando
CF
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
C121001:NR2B NMDA receptor; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C104723:glutamate receptor ionotropic, AMPA 3; D000431:Ethanol; C104722:glutamate receptor ionotropic, AMPA 2