Atomoxetine reverses attentional deficits produced by noradrenergic deafferentation of medial prefrontal cortex.

Academic Article


  • BACKGROUND: The majority of studies assessing executive function in attention deficit disorder (ADD) have shown deficits in attentional set shifting using either the Wisconsin card sorting task or the intra-dimensional/extra-dimensional set-shifting task (ID/ED). Damage to the prefrontal cortex in humans, primates, and rodents impairs extra-dimensional (ED) shifts. Noradrenergic depletion of the medial prefrontal cortex in rats is sufficient to impair attentional set shifting. Atomoxetine, a selective norepinephrine (NE) re-uptake inhibitor, is hypothesized to produce beneficial effects in patient with ADD by augmenting NE release in prefrontal cortex. MATERIALS AND METHODS: We assessed the effects of systemic administration of atomoxetine (0.0, 0.1, 0.3, and 0.9 mg/kg/ml) in normal and noradrenergically lesioned (NE-LX) rats on attentional-set shifts. We replicated findings showing NE-LX rats are selectively impaired on the ED shifts but not reversals or other discriminations. RESULTS: Atomoxetine remediated the attentional set-shifting impairments in NE-LX rats but impaired ED performance of non-lesioned rats. DISCUSSION: Though atomoxetine is neurochemically selective, it is not wholly specific at doses >0.3 mg/kg. All doses of the drug were similar in their efficacy in reversing the ED deficit, but the effectiveness of the 0.1 mg/kg dose supports the hypothesis that increases in prefrontal NE alone are sufficient to improve attention in NE-LX rats. Moreover, the detrimental effects of the drug in non-lesioned rats support the hypothesis that optimal levels of NE in prefrontal cortex are critical to attentional set shifting with both supra- and sub-optimal levels producing attentional impairments.
  • Authors

  • Newman, Lori A
  • Darling, Jenna
  • McGaughy, Jill
  • Status

    Publication Date

  • September 2008
  • Published In

  • Psychopharmacology  Journal
  • Keywords

  • Adrenergic Uptake Inhibitors
  • Animals
  • Atomoxetine Hydrochloride
  • Attention
  • Attention Deficit Disorder with Hyperactivity
  • Behavior, Animal
  • Discrimination Learning
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Norepinephrine
  • Prefrontal Cortex
  • Propylamines
  • Psychomotor Performance
  • Rats
  • Rats, Long-Evans
  • Digital Object Identifier (doi)

    Start Page

  • 39
  • End Page

  • 50
  • Volume

  • 200
  • Issue

  • 1