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.
KeywordsAttention Learning Set-shifting Behavioral flexibility Rat Norepinephrine Prefrontal cortex ADHD Schizophrenia
- Koda K, Ago Y, Cong Y et al (2010) Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice. J Neurochem 114:259–270. doi:10.1111/j.1471-4159.2010.06750.x PubMedGoogle Scholar
- Pedersen CS, Goetghebeur P, Dias R (2009) Chronic infusion of PCP via osmotic mini-pumps: a new rodent model of cognitive deficit in schizophrenia characterized by impaired attentional set-shifting (ID/ED) performance. J Neurosci Methods 185:66–69. doi:10.1016/j.jneumeth.2009.09.014 CrossRefPubMedGoogle Scholar
- Sun H, Cocker PJ, Zeeb FD, Winstanley CA (2011) Chronic atomoxetine treatment during adolescence decreases impulsive choice, but not impulsive action, in adult rats and alters markers of synaptic plasticity in the orbitofrontal cortex. Psychopharmacology 219:285–301. doi:10.1007/s00213-011-2419-9 CrossRefPubMedGoogle Scholar