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Rats were examined for cognitive flexibility using the attentional set-shifting task (adapted from26). A rectangular arena divided into three quadrants was used for the testing arena. One quadrant was marked as the start box, while the remaining quadrants contained pots defined by a pair of cues along two stimulus dimensions: odor and digging medium. Rats were food restricted (80% of normal dietary intake) for a minimum of seven days prior to the testing day. A ‘Cheerio’ (toasted whole grain cereal) reward was placed at the bottom of the “positive” pot and buried in the digging medium. Rats were then trained to reliably dig in pots to obtain the reward during the habituation period. The following day, rats underwent training in which they were taught simple discrimination tasks, to reach a criterion of six consecutive correct trials. On the day of testing, rats were exposed to a series of tasks of increasing difficulty that included a compound discrimination (CD), an intra-dimensional shift (ID), two reversals (R1 and R2) and an extra-dimensional shift (ED). The testing portion of AST typically took 3–8 h to complete per rat. Based on our previously published work27, and that of others28, we anticipated deficits in reversal learning (R1) and ED, that were analyzed by one-way ANOVA, followed by a Holm–Sidak post hoc test. The experimenter was blinded to the treatment of the subject during all portions of AST.

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