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  • The International Journal of Neuropsychopharmacology, Volume 16, Issue 4
  • May 2013, pp. 919-924

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

  • Carly Kiselycznyk (a1) (a2), Xiaoqun Zhang (a1), Richard L. Huganir (a3), Andrew Holmes (a2) and Per Svenningsson (a1)
  • DOI:
  • Published online: 29 January 2013

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 Ser831 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.

Corresponding author
Address for correspondence: Dr C. Kiselycznyk, 300 George St., Suite 901, New Haven, CT 06511-6662, USA. Tel.: +1 203 785 2157Fax: +1 203 785 7357Email:
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  • ISSN: 1461-1457
  • EISSN: 1469-5111
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