IMR Press / FBS / Volume 10 / Issue 2 / DOI: 10.2741/S518

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


Molecular role of dopamine in anhedonia linked to reward deficiency syndrome (RDS) and anti- reward systems

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1 Department of Psychiatry, McKnight Brain Institute, University of Florida, College of Medicine, Gainesville, FL, USA
2 Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
3 Global Integrated Services Unit University of Vermont Center for Clinical and Translational Science, College of Medicine, Burlington, VT, USA
4 Department of Addiction Research, Dominion Diagnostics, LLC, North Kingstown, RI, USA
5 Center for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purbe Medinpur, West Bengal, India
6 Division of Neuroscience Research and Therapy, The Shores Treatment and Recovery Center, Port St. Lucie, Fl., USA
7 Division of Nutrigenomics, Sanus Biotech, Austin TX, USA
8 Department of Psychiatry, Washington University School of Medicine, St. Louis, Mo, USA
9 Department of Psychology, Curry College, Milton, MA, USA
10 Department of Psychiatry, Wright State University, Boonshoft School of Medicine, Dayton, OH, USA

*Author to whom correspondence should be addressed.

Front. Biosci. (Schol Ed) 2018, 10(2), 309–325;
Published: 1 January 2018

Anhedonia is a condition that leads to the loss of feelings pleasure in response to natural reinforcers like food, sex, exercise, and social activities. This disorder occurs in addiction, and an array of related neuropsychiatric syndromes, including schizophrenia, depression, and Post Traumatic Stress Disorder (PTSD). Anhedonia may by due to derangements in mesolimbic dopaminergic pathways and their terminal fields (e.g., striatum, amygdala, and prefrontal cortex) that persist long after the traces of the causative drugs are eliminated (pharmacokinetically). Here we postulate that anhedonia is not a distinct entity but is rather an epiphenomenon of hypodopaminergic states and traits arising from the interaction of genetic traits and epigenetic neurobiological alterations in response to environmental influences. Moreover, dopaminergic activity is rather complex, and so it may give rise to differential pathophysiological processes such as incentive sensitization, aberrant learning and stress-like “anti-reward” phenomena. These processes may have additive, synergistic or antagonistic interactions with the concurrent reward deficiency states leading in some instances to more severe and long-lasting symptoms. Operant understanding of the neurogenetic antecedents to reward deficiency syndrome (RDS) and the elucidation of reward gene polymorphisms may provide a map for accessing an individual’s genetic risk for developing Anhedonia. Prevention techniques that can restore homeostatic balance via physiological activation of dopaminergic receptors (D2/D3) may be instrumental for targeting not only anhedonia per se but also drug craving and relapse.

Reward Deficiency Syndrome
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