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.
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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. / Kiefer, Falk; Jahn, Holger; Koester, Anja; Montkowski, Alexandra; Reinscheid, Rainer K; Wiedemann, Klaus.
In: BIOL PSYCHIAT, Vol. 53, No. 4, 4, 2003, p. 345-351.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 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.
AU - Kiefer, Falk
AU - Jahn, Holger
AU - Koester, Anja
AU - Montkowski, Alexandra
AU - Reinscheid, Rainer K
AU - Wiedemann, Klaus
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 53
SP - 345
EP - 351
JO - BIOL PSYCHIAT
JF - BIOL PSYCHIAT
SN - 0006-3223
IS - 4
M1 - 4
ER -