Tolerance to ethanol intoxication after chronic ethanol: role of GluN2A and PSD-95

Rachel A. Daut; Erica F. Busch; Jessica Ihne; Daniel Fisher; Masayoshi Mishina; Seth G. N. Grant; Marguerite Camp; Andrew Holmes

doi:10.1111/adb.12110

Tolerance to ethanol intoxication after chronic ethanol: role of GluN2A and PSD-95

Rachel A. Daut, Erica F. Busch, Jessica Ihne, Daniel Fisher, Masayoshi Mishina, Seth G. N. Grant, Marguerite Camp, Andrew Holmes^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

The neural and genetic factors underlying chronic tolerance to alcohol are currently unclear. The GluN2AN-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 C57BL/6J, GluN2A or PSD-95 knockout mice assayed 2-3 days later. However, significant tolerance to LORR was evident 1 day after CIE in C57BL/6J and PSD-95 knockouts, but absent in GluN2A knockouts. These data suggest a role for GluN2A in tolerance, extending evidence that human GluN2A gene variation is involved in alcohol dependence.

Original language	English
Pages (from-to)	259-262
Number of pages	4
Journal	Addiction Biology
Volume	20
Issue number	2
Early online date	7 Jan 2014
DOIs	https://doi.org/10.1111/adb.12110
Publication status	Published - Mar 2015

Keywords

chronic ethanol
GluN2A and PSD-95
tolerance
CHRONIC INTERMITTENT ETHANOL
NMDA RECEPTOR NR2A
MICE
DEPENDENCE
ASSOCIATION
ALCOHOLISM
MODULATION
SUBUNIT

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@article{e69a6feb99924cc9b4ec16680f780e6e,

title = "Tolerance to ethanol intoxication after chronic ethanol: role of GluN2A and PSD-95",

abstract = "The neural and genetic factors underlying chronic tolerance to alcohol are currently unclear. The GluN2AN-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 C57BL/6J, GluN2A or PSD-95 knockout mice assayed 2-3 days later. However, significant tolerance to LORR was evident 1 day after CIE in C57BL/6J and PSD-95 knockouts, but absent in GluN2A knockouts. These data suggest a role for GluN2A in tolerance, extending evidence that human GluN2A gene variation is involved in alcohol dependence.",

keywords = "chronic ethanol, GluN2A and PSD-95, tolerance, CHRONIC INTERMITTENT ETHANOL, NMDA RECEPTOR NR2A, MICE, DEPENDENCE, ASSOCIATION, ALCOHOLISM, MODULATION, SUBUNIT",

author = "Daut, {Rachel A.} and Busch, {Erica F.} and Jessica Ihne and Daniel Fisher and Masayoshi Mishina and Grant, {Seth G. N.} and Marguerite Camp and Andrew Holmes",

year = "2015",

month = mar,

doi = "10.1111/adb.12110",

language = "English",

volume = "20",

pages = "259--262",

journal = "Addiction Biology",

issn = "1355-6215",

publisher = "Wiley",

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T1 - Tolerance to ethanol intoxication after chronic ethanol

T2 - role of GluN2A and PSD-95

AU - Daut, Rachel A.

AU - Busch, Erica F.

AU - Ihne, Jessica

AU - Fisher, Daniel

AU - Mishina, Masayoshi

AU - Grant, Seth G. N.

AU - Camp, Marguerite

AU - Holmes, Andrew

PY - 2015/3

Y1 - 2015/3

N2 - The neural and genetic factors underlying chronic tolerance to alcohol are currently unclear. The GluN2AN-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 C57BL/6J, GluN2A or PSD-95 knockout mice assayed 2-3 days later. However, significant tolerance to LORR was evident 1 day after CIE in C57BL/6J and PSD-95 knockouts, but absent in GluN2A knockouts. These data suggest a role for GluN2A in tolerance, extending evidence that human GluN2A gene variation is involved in alcohol dependence.

AB - The neural and genetic factors underlying chronic tolerance to alcohol are currently unclear. The GluN2AN-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 C57BL/6J, GluN2A or PSD-95 knockout mice assayed 2-3 days later. However, significant tolerance to LORR was evident 1 day after CIE in C57BL/6J and PSD-95 knockouts, but absent in GluN2A knockouts. These data suggest a role for GluN2A in tolerance, extending evidence that human GluN2A gene variation is involved in alcohol dependence.

KW - chronic ethanol

KW - GluN2A and PSD-95

KW - tolerance

KW - CHRONIC INTERMITTENT ETHANOL

KW - NMDA RECEPTOR NR2A

KW - MICE

KW - DEPENDENCE

KW - ASSOCIATION

KW - ALCOHOLISM

KW - MODULATION

KW - SUBUNIT

U2 - 10.1111/adb.12110

DO - 10.1111/adb.12110

M3 - Article

VL - 20

SP - 259

EP - 262

JO - Addiction Biology

JF - Addiction Biology

SN - 1355-6215

IS - 2

ER -

Tolerance to ethanol intoxication after chronic ethanol: role of GluN2A and PSD-95

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Keywords

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