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 GluN2A 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 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.

journal_name

Addict Biol

journal_title

Addiction biology

authors

Daut RA,Busch EF,Ihne J,Fisher D,Mishina M,Grant SG,Camp M,Holmes A

doi

10.1111/adb.12110

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

259-62

issue

2

eissn

1355-6215

issn

1369-1600

journal_volume

20

pub_type

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