-Original-

Acute Atomoxetine Selectively Modulates Encoding of Reward Value in Ventral Medial Prefrontal Cortex

Chihiro Suzuki¹, Yumiko Ikeda², Amane Tateno³, Yoshiro Okubo³, Haruhisa Fukayama¹ and Hidenori Suzuki²

¹Anesthesiology and Clinical Physiology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
²Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
³Department of Neuropsychiatry, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

Background: A recent neurocognitive model of attention-deficit hyperactivity disorder (ADHD) has proposed a primary deficit in reward function as well as in executive function to account for underlying neural substrates of ADHD symptoms. Atomoxetine has been widely used as a non-stimulant medication for ADHD with little abuse liability. Although animal studies have reported that atomoxetine increases extracellular levels of both noradrenaline and dopamine in the prefrontal cortex, which receives input from a mesocorticolimbic pathway involved in reward function, there have been few studies in humans concerning the effects of atomoxetine in terms of reward function. Therefore, we investigated whether a single dose of atomoxetine (acute atomoxetine) affects reward processing in healthy adults.
Methods: We used functional magnetic resonance imaging and adopted the monetary incentive delay task to separately examine neural responses to monetary reward anticipation in the nucleus accumbens and outcome in the ventral medial prefrontal cortex (vmPFC). The experiment was designed as a randomized, placebo-controlled within-subjects cross-over trial. Fourteen healthy adults completed two series of studies, taking either atomoxetine or placebo.
Results: Atomoxetine significantly decreased vmPFC activation during gain outcome compared to placebo. In gain anticipation, however, atomoxetine did not show a significant increase in the nucleus accumbens activation compared with placebo.
Conclusions: These results suggest that atomoxetine affects reward value encoding through selective modulation of vmPFC activity related to reward outcome. Therefore, such modulatory action may partly contribute to a therapeutic effect of atomoxetine for a group of ADHD patients with increased activity in vmPFC.

J Nippon Med Sch 2019; 86: 98-107

Keywords
atomoxetine, functional MRI, monetary incentive delay task, reward value encoding, ventral medial prefrontal cortex

Correspondence to
Hidenori Suzuki, MD, PhD, Department of Pharmacology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
hsuzuki@nms.ac.jp

Received, December 13, 2018
Accepted, December 28, 2018