Effects of the Non-Stimulant Norepinephrine Reuptake Inhibitor, Atomoxetine, on Cognitive Flexibility in Healthy Adult Long-Evans Rats

Executive function is the control of multiple higher order cognitive processes that include attention, working memory, and cognitive flexibility. Cognitive flexibility is the ability to shift behavioral strategies in response to changing environmental demands and task complexity. This cognitive modality is often impaired in many neuropsychiatric disorders like attention deficit hyperactivity disorder (ADHD). Deficits in cognitive flexibility are associated with dysregulation of the catecholamines, norepinephrine (NE) and dopamine (DA) within the prefrontal cortex (PFC). Atomoxetine (ATX), a non-stimulant NE reuptake inhibitor, elevates levels of NE and DA in the PFC by inhibiting the norepinephrine transporter (NET). ATX is used to treat ADHD and improves components of cognitive flexibility in rodent models of cognitive disorder. However, the effects of ATX on cognitive flexibility in healthy adult rats have not been demonstrated. Within the current study, an automated operant strategy shifting task (SST) of cognitive flexibility was used to examine the effects of ATX (0.3-1mg/kg) on performance in male and female Long-Evans rats. Rats initially acquired a visual cue strategy to collect sucrose reward pellets. Twenty-four hours after initial acquisition, rats were assessed for retrieval of the visual cue strategy followed by a series of strategy shifting and reversal learning challenges.