Work

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

Year: 2013

Type: article

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-HT(1A) agonist, and diazepam, a benzodiazepine, influence phosphorylation of GluA1 subunits of AMPA receptors at the potentiating residue Ser(845) and Ser(831) in corticolimbic regions. To test the functional relevance of these changes, phosphomutant GluA1 mice lacking phosphorylatable Ser(845) 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.

Source: The International Journal of Neuropsychopharmacology

DOI: 10.1017/s1461145712001174

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

Institutions: Karolinska Institutet, National Institute on Alcohol Abuse and Alcoholism, Johns Hopkins University

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: National Institutes of Health