title: Do GluA1 knockout mice exhibit behavioral abnormalities relevant to the negative or cognitive symptoms of schizophrenia and schizoaffective disorder?
abstract: The glutamate system has been strongly implicated in the pathophysiology of psychotic illnesses, including schizophrenia and schizoaffective disorder. We recently found that knockout (KO) mice lacking the AMPA GluA1 subunit displayed behavioral abnormalities relevant to some of the positive symptoms of these disorders. Here we phenotyped GluA1 KO mice for behavioral phenotypes pertinent to negative and cognitive/executive symptoms. GluA1 KO mice were tested for conspecific social interactions, the acquisition and extinction of an operant response for food-reward, operant-based pairwise visual discrimination and reversal learning, and impulsive choice in a delay-based cost/benefit decision-making T-maze task. Results showed that GluA1 KO mice engaged in less social interaction than wildtype (WT) controls when tested in a non-habituated, novel environment, but, conversely, displayed more social interaction in a well habituated, familiar environment. GluA1 KO mice were faster to acquire an operant stimulus-response for food reward than WT and were subsequently slower to extinguish the response. Genotypes showed similar pairwise discrimination learning and reversal, although GluA1 KO mice made fewer errors during early reversal. GluA1 KO mice also displayed increased impulsive choice, being less inclined to choose a delayed, larger reward when given a choice between this and a smaller, immediate reward, compared to WT mice. Finally, sucrose preference did not differ between genotypes. Collectively, these data add to the growing evidence that GluA1 KO mice display at least some phenotypic abnormalities mimicking those found in schizophrenia/schizoaffective disorder. Although these mice, like any other single mutant line, are unlikely to model the entire disease, they may nevertheless provide a useful tool for studying the role of GluA1 in certain aspects of the pathophysiology of major psychotic illness.
authors.affiliation: Department of Experimental Psychology, South Parks Road, University of Oxford, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Barkus
authors.forename: Michael
authors.initials: M
authors.lastname: Feyder
authors.forename: Carolyn
authors.initials: C
authors.lastname: Graybeal
authors.forename: Tara
authors.initials: T
authors.lastname: Wright
authors.forename: Lisa
authors.initials: L
authors.lastname: Wiedholz
authors.forename: Alicia
authors.initials: A
authors.lastname: Izquierdo
authors.forename: Carly
authors.initials: C
authors.lastname: Kiselycznyk
authors.forename: Wolfram
authors.initials: W
authors.lastname: Schmitt
authors.forename: David J
authors.initials: DJ
authors.lastname: Sanderson
authors.forename: J Nicholas P
authors.initials: JN
authors.lastname: Rawlins
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Saksida
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bussey
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
authors.forename: David
authors.initials: D
authors.lastname: Bannerman
authors.forename: Andrew
authors.initials: A
authors.lastname: Holmes
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D011618:Psychotic Disorders / Q000235:genetics / Q000378:metabolism*; D018091:Receptors, AMPA / Q000172:deficiency* / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D012919:Social Behavior
chemical_list: D018091:Receptors, AMPA