Reduced phosphorylation of GluA1 subunits relates to anxiety-like behaviours in mice

Carly Kiselycznyk, Xiaoqun Zhang, Richard L. Huganir, Andrew Holmes, Per Svenningsson

Research output: Contribution to journalArticle

Abstract

Anxiety and depression are highly prevalent and frequently co-morbid conditions. The ionotropic glutamate receptors N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) mediate actions of monoaminergic antidepressants and have been directly targeted by novel fast-acting antidepressants. Less is known about the role of these receptors in anxiety-like states. Here we investigate how two distinct anxiolytic agents, buspirone, a partial 5-HT1A agonist, and diazepam, a benzodiazepine, influence phosphorylation of GluA1 subunits of AMPA receptors at the potentiating residue Ser845 and Ser831 in corticolimbic regions. To test the functional relevance of these changes, phosphomutant GluA1 mice lacking phosphorylatable Ser845 and Ser 831 were examined in relevant behavioural paradigms. These mutant mice exhibited a reduced anxiety-like phenotype in the light/dark exploration task and elevated plus maze, but not in the novelty induced hypophagia paradigm. These data indicate that reduced potentiation of the AMPA receptor signalling, via decreased GluA1 phoshorylation, is specifically involved in approach-avoidance based paradigms relevant for anxiety-like behaviours.

Original languageEnglish (US)
Pages (from-to)919-924
Number of pages6
JournalInternational Journal of Neuropsychopharmacology
Volume16
Issue number4
DOIs
StatePublished - May 1 2013

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Keywords

  • AMPA
  • glutamate
  • hippocampus
  • mutant mice

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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