Tolerance to ethanol intoxication after chronic ethanol: role of GluN2A and PSD‐95. (7th January 2014)

• Record Type: Journal Article
• Authors: Daut, Rachel A.; Busch, Erica F.; Ihne, Jessica; Fisher, Daniel; Mishina, Masayoshi; Grant, Seth G. N.; Camp, Marguerite; Holmes, Andrew
• Is Part Of: Addiction biology. Volume 20:Number 2(2015:Mar.)
• Page Start: 259
• Page End: 262
• Publication Date: 2014-01-07
• Subjects: Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12110
• Languages: English
• ISSNs: 1355-6215

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>The neural and genetic factors underlying chronic tolerance to alcohol are currently unclear. The GluN2A <italic>N</italic>‐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.</p> </abstract>