Atomoxetine accelerates attentional set shifting without affecting learning rate in the rat

Shifting to a new rule is a form of behavioral flexibility that is impaired in numerous psychiatric and neurological illnesses. Animal studies have revealed that this form of flexibility depends upon norepinephrine (NE) neurotransmission. Atomoxetine, a NE reuptake inhibitor, improves performance of humans in set shifting tasks. Our objective was to validate its effects in a rodent set shifting task. We tested the drug effect using an operant task that required a shift from a visual cue-guided behavior to a novel location-guided rule. A 1.0-mg/kg dose significantly accelerated rule shifting without affecting learning strategies, such as win-stay or lose-shift. Fitting behavioral performance with a learning function provided a measure of learning rate. This novel analysis revealed that atomoxetine accelerated shifting to the new rule without affecting learning rate.