Involvement of NMDA receptors in alcohol-mediated behavior: mice with reduced affinity of the NMDA R1 glycine binding site display an attenuated sensitivity to ethanol.
BACKGROUND
Ethanol antagonizes central effects of glutamate by inhibition of the N-methyl-D-aspartate (NMDA) receptor function. The co-agonist glycine has been shown to reverse alcohol-mediated effects. The aim of this study was to evaluate the influence of the glycine binding site of the NMDA receptor on the behavioral effects of alcohol by investigating mice with an 80% reduced affinity of the NMDA R1 subunit for glycine (Grin1(D481N)).


METHODS
Free-choice and forced alcohol intake was studied over a period of 52 days. Anxiolytic activity (elevated plus maze, open field) and motor coordination (rotarod) was tested after 3 days of forced alcohol intake and during ethanol withdrawal.


RESULTS
In contrast to wild-type mice, alcohol-associated anxiolysis and motor impairment was attenuated in Grin1(D481N) mice during intoxication. Free-choice alcohol intake did not differ between wild-type and Grin1(D481N) mice.


CONCLUSIONS
Our results give first evidence in vivo for a possible role of an altered NMDA-receptor complex with a hyposensitive glycine binding site for behavioral effects mediated by ethanol.
Kiefer
Falk
F
Department of Psychiatry, University Hospital of Hamburg, Hamburg, Germany.
Jahn
Holger
H
Koester
Anja
A
Montkowski
Alexandra
A
Reinscheid
Rainer K
RK
Wiedemann
Klaus
K
D000428:Alcohol Drinking / Q000235:genetics / Q000523:psychology; D000435:Alcoholic Intoxication / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000523:psychology; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D002492:Central Nervous System Depressants; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol