Atomoxetine accelerates attentional set shifting without affecting learning rate in the rat
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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.
KeywordsAttention Learning Set-shifting Behavioral flexibility Rat Norepinephrine Prefrontal cortex ADHD Schizophrenia
We thank G. Katakalidis and D. Vasilyev for training animals. We also thank A. Dwarakanath for the technical assistance with the psigfit MATLAB toolbox.
This work was funded by a Marie Curie fellowship to N.K.T. (PIIF-GA-2012-331122) in the European Union FP7 funding scheme and the Max Planck Society.
Conflict of interest
The authors declare that they have no competing interests.
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