Affordable Access

Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?

Authors
Journal
Neurobiology of Disease
0969-9961
Publisher
Elsevier
Publication Date
Volume
40
Issue
3
Identifiers
DOI: 10.1016/j.nbd.2010.08.005
Keywords
  • Animals
  • Antimanic Agents
  • Behavior
  • Animal
  • Central Nervous System Stimulants
  • Disease Models
  • Animal
  • Gene Deletion
  • Lithium Compounds
  • Mice
  • Mice
  • Inbred C57Bl
  • Mice
  • Knockout
  • Phenotype
  • Psychotic Disorders
  • Receptors
  • Ampa

Abstract

Glutamatergic dysfunction is strongly implicated in schizophrenia and mood disorders. GluA1 knockout (KO) mice display schizophrenia- and depression-related abnormalities. Here, we asked whether GluA1 KO show mania-related abnormalities. KO were tested for behavior in approach/avoid conflict tests, responses to repeated forced swim exposure, and locomotor responses under stress and after psychostimulant treatment. The effects of rapid dopamine depletion and treatment with lithium or a GSK-3β inhibitor (SB216763) on KO locomotor hyperactivity were tested. Results showed that KO exhibited novelty- and stress-induced locomotor hyperactivity, reduced forced swim immobility and alterations in approach/avoid conflict tests. Psychostimulant treatment and dopamine depletion exacerbated KO locomotor hyperactivity. Lithium, but not SB216763, treatment normalized KO anxiety-related behavior and partially reversed hyperlocomotor behavior, and also reversed elevated prefrontal cortex levels of phospho-MARCKS and phospho-neuromodulin. Collectively, these findings demonstrate mania-related abnormalities in GluA1 KO and, combined with previous findings, suggest this mutant may provide a novel model of features of schizoaffective disorder.

There are no comments yet on this publication. Be the first to share your thoughts.