Anxiety modulates cognitive deficits in a perinatal glutathione deficit animal model of schizophrenia.

In this study, we investigated long-term repercussion of early glutathione deficit by l-buthionine-(S,R)-sulfoximine (BSO) injections as a rat model of schizophrenia. BSO rats were tested through various behavioral tasks requiring animals to take into account previously delivered information. We showed that relative to controls, BSO rats (1) were less active and more anxious in an Elevated Plus Maze test, allowing us to split them into two subgroups with high and low anxiety levels; (2) demonstrated normal abilities of behavioral flexibility tested with a rat-adapted version of the Wisconsin Card Sorting Test (WCST), with even higher abilities in anxious BSO rats suggesting reduced interference of previously acquired rules; (3) did not forage normally in radial arm mazes and mainly used clockwise strategies; (4) exhibited a lack of habituation during a startle response task; and (5) showed a normal prepulse inhibition of the startle response (PPI) and a normal conditioned taste aversion (CTA). All these results indicate that early glutathione deficit provokes persistent changes in adulthood and improves the validity of this animal model of schizophrenia. They further suggest difficulties binding temporally separated events (WCST), except when the salience of this information is very strong (CTA). We propose that the transient glutathione deficit during cerebral development could alter a "cognitive binding" process in interaction with the emotional state that could possibly account for the disruption of integrative function that characterizes schizophrenia.