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Schlagwörter:
Glutamate Schizophrenia Schizoaffective Cognition Executive function Knockout
Zusammenfassung:
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 toWT 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
