The role of dopamine in the pathophysiology and treatment of apathy

T.T.-J. Chong, Masud Husain

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

66 Citations (Scopus)


Disorders of diminished motivation, such as apathy, are common and prevalent across a wide range of medical conditions, including Parkinson's disease, Alzheimer's dementia, stroke, depression, and schizophrenia. Such disorders have a significant impact on morbidity and quality of life, yet their management lacks consensus and remains unsatisfactory. Here, we review laboratory and clinical evidence for the use of dopaminergic therapies in the treatment of apathy. Dopamine is a key neurotransmitter that regulates motivated decision making in humans and other species. A large corpus of evidence suggests that it plays an important role in promoting approach behavior by attributing incentive salience to reward stimuli, and facilitating the overcoming of effort costs. Furthermore, dopaminergic neurons innervate several frontostriatal structures that mediate reward-guided behavior. Based on these findings, there are a priori reasons for considering dopamine in the treatment of disorders of diminished motivation. We highlight key studies that have attempted to use dopamine to manage patients with apathy, and that collectively offer cautious evidence in favor of its efficacy. However, many of these studies are small, unblinded, and uncontrolled, and utilize subjective, questionnaire-based measures of apathy. Given the development of novel paradigms which are able to objectively dissect motivational dysfunction, we are now well positioned to quantify the effect of specific classes of dopaminergic medication on reward- and effort-based decision making in apathy. We anticipate that such paradigms will lay the foundation for future studies to evaluate new and existing treatments for disorders of motivation, using sensitive measures of apathy as primary quantifiable end points.

Original languageEnglish
Title of host publicationProgress in Brain Research
EditorsBettina Studer, Stefan Knecht
Number of pages42
ISBN (Print)9780444637017
Publication statusPublished - 2016

Publication series

NameProgress in Brain Research
ISSN (Print)00796123
ISSN (Electronic)18757855


  • Apathy
  • Decision making
  • Disorders of motivation
  • Dopamine
  • Effort
  • Motivation
  • Reward

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