Expression of N-methyl-d-aspartate (NMDA) receptor subunits and splice variants in an animal model of long-term voluntary alcohol self-administration.
Long-term, free-choice, alcohol self-administration with repeated alcohol deprivation phases is known to enhance N-methyl-d-aspartate (NMDA) receptor activity. We hypothesized that this might not only reflect an increase in NMDA receptor density, but that differential transcriptional regulation and alternative splicing of the various subunits comprising the NMDA receptor may lead to changes in receptor composition and subsequent function. We, therefore, aimed to further investigate this effect in various brain regions. The relative mRNA expression of exon 5 inclusion/exclusion variants of the NR1 subunit, and the relative expression of NR2A, NR2B and NR2C subunits was examined in rats subjected to long-term free-choice, alcohol self-administration with repeated alcohol deprivation phases. We observed a relative decrease of the NR2C/NR2A mRNA ratio and an increase of NR1 splice variants including exon 5 (NR1+E5) in the striatum but not in the cortex, hippocampus or cerebellum in the experimental group. Our results demonstrate that long-term voluntary alcohol self-administration, affects the regulation of genes encoding the various subunits and splice variants of the NMDA receptor in a brain regional-specific manner.
Raeder
Hanna
H
Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
Holter
Sabine M
SM
Hartmann
Annette M
AM
Spanagel
Rainer
R
Moller
Hans-Juergen
HJ
Rujescu
Dan
D
D000437:Alcoholism / Q000235:genetics / Q000378:metabolism; D017398:Alternative Splicing / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D005091:Exons / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D021122:Protein Subunits / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012646:Self Administration / Q000379:methods*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D014018:Tissue Distribution
C120997:NR2A NMDA receptor; C432823:NR2C NMDA receptor; D010446:Peptide Fragments; D021122:Protein Subunits; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol