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Behavioral flexibility is a cognitive process depending on prefrontal areas allowing adaptive responses to environmental changes. Serotonin transporter knockout (5-HTT−/−) rodents show improved reversal learning in addition to orbitofrontal cortex changes. Another form of behavioral flexibility, extradimensional strategy set-shifting (EDSS), heavily depends on the medial prefrontal cortex. This region shows functional changes in 5-HTT−/− rodents as well. Here we subjected 5-HTT−/− rats and their wild-type counterparts to an EDSS paradigm and a supplementary latent inhibition task. Results indicate that 5-HTT−/− rats also show improved EDSS, and indicate that reduced latent inhibition may contribute as an underlying mechanism.