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Tolerance to ethanol intoxication after chronic ethanol: role of G lu N 2 A and PSD ‐95
Author(s) -
Daut Rachel A.,
Busch Erica F.,
Ihne Jessica,
Fisher Daniel,
Mishina Masayoshi,
Grant Seth G. N.,
Camp Marguerite,
Holmes Andrew
Publication year - 2015
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12110
Subject(s) - ethanol , knockout mouse , receptor , alcohol , alcohol tolerance , gene knockout , nmda receptor , protein subunit , medicine , chemistry , endocrinology , gene , biochemistry
Abstract The neural and genetic factors underlying chronic tolerance to alcohol are currently unclear. The G lu N 2 A N ‐methyl‐D‐aspartate receptors ( NMDAR ) subunit and the NMDAR ‐anchoring protein PSD ‐95 mediate acute alcohol intoxication and represent putative mechanisms mediating tolerance. We found that chronic intermittent ethanol exposure ( CIE ) did not produce tolerance [loss of righting reflex ( LORR )] or withdrawal‐anxiety in C 57 BL /6 J , G lu N 2 A or PSD ‐95 knockout mice assayed 2–3 days later. However, significant tolerance to LORR was evident 1 day after CIE in C 57 BL /6 J and PSD ‐95 knockouts, but absent in G lu N 2 A knockouts. These data suggest a role for G lu N 2 A in tolerance, extending evidence that human G lu N 2 A gene variation is involved in alcohol dependence.