The International Journal of Neuropsychopharmacology

Brief Report

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

Carly Kiselycznyka1a3 c1, Xiaoqun Zhanga1, Richard L. Huganira2, Andrew Holmesa3 and Per Svenningssona1

a1 Laboratory of Translational Neuropharmacology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

a2 The Solomon H. Snyder Department of Neuroscience, John Hopkins University, Baltimore, MD, USA

a3 Laboratory for Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA

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 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.

(Received February 20 2012)

(Reviewed March 26 2012)

(Revised July 31 2012)

(Accepted September 04 2012)

(Online publication January 29 2013)

Key words

  • AMPA;
  • glutamate;
  • hippocampus;
  • mutant mice

Correspondence

c1 Address for correspondence: Dr C. Kiselycznyk, 300 George St., Suite 901, New Haven, CT 06511-6662, USA. Tel.: +1 203 785 2157 Fax: +1 203 785 7357 Email: carly.kiselycznyk@yale.edu