Abstract
Rationale
The nucleus accumbens (NAc) works as a key brain structure of the reward system, in which reward-related neural activity is well correlated with dopamine release from mesolimbic dopaminergic neurons.
Objectives
Since modafinil can modulate dopaminergic transmission through re-uptake inhibition of dopamine, we investigated whether modafinil affects the reward-related brain activity in the NAc in healthy subjects.
Methods
Twenty healthy participants underwent two series of functional magnetic resonance imaging while performing monetary incentive delay task in which they were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money, under modafinil or placebo condition. Blood oxygenation-level dependent (BOLD) activation signals during gain and loss anticipations were analyzed in the NAc as an a priori region of interest as well as the whole brain.
Results
Modafinil significantly changed subjective feelings toward positive ones. The activation of BOLD signals was observed during gain anticipation under the placebo and modafinil conditions in the left and bilateral NAc, respectively. The modafinil condition showed significantly higher BOLD signal change at the highest gain (+¥500) cue compared to the placebo condition.
Conclusions
The present study showed that modafinil affects reward processing in the NAc in healthy subjects through enhancing more positive anticipation, and it may provide a basis for the use of this drug for treating anhedonia observed in psychiatric disorders.
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Acknowledgements
We thank Dr. Knutson for his helpful advice on the MID task, Mr. Nagaya, Mr. Kanaya, Mr. Suda, Ms. Takei and Mr. Sakurai (Clinical Imaging Center for Healthcare, Nippon Medical School) for their assistance in performing the MRI examinations. We also thank Ms. Kishi and Ms. Fukano for help as clinical research coordinators and Dr. Gerz for his English editing of our manuscript. This study was supported by a Grant-in-Aid for Encouragement of Young Scientists (B) (24791237 to Y.I.) and a Grant-in-Aid for Challenging Exploratory Research (22659212 to Y.O.) from the Japan Society for the Promotion of Science, and a grant (S0801035 to H.S.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
Conflict of interest statement
Dr. Suzuki has received speaker's honoraria from Pfizer and Eisai within the past 3 years. Dr. Okubo has received grants or speaker's honoraria from Dainippon Sumitomo Pharma, GlaxoSmithKline, Janssen Pharmaceutical, Otsuka, Pfizer, Eli Lilly, Astellas, Yoshitomi, and Meiji within the past 3 years. For the remaining authors, none were declared.
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Funayama, T., Ikeda, Y., Tateno, A. et al. Modafinil augments brain activation associated with reward anticipation in the nucleus accumbens. Psychopharmacology 231, 3217–3228 (2014). https://doi.org/10.1007/s00213-014-3499-0
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DOI: https://doi.org/10.1007/s00213-014-3499-0