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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.

SUBMITTER: Daut RA

PROVIDER: S-EPMC4085154 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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

Daut Rachel A RA Busch Erica F EF Ihne Jessica J Fisher Daniel D Mishina Masayoshi M Grant Seth G N SG Camp Marguerite M Holmes Andrew A

Addiction biology 20140107 2

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, sig ...[more]

PMID: 24397780

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