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

Research output: Contribution to journalArticle

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

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)259-262
Number of pages4
JournalAddiction Biology
Volume20
Issue number2
Early online date7 Jan 2014
DOIs
Publication statusPublished - Mar 2015

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.

    Research areas

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

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