The role of the brain reward system in depression

Naranjo, Claudio A.; Tremblay, Lescia K.; Busto, Usoa E.

doi:10.1016/s0278-5846(01)00156-7

Cited by 245Neurotransmitter Receptor Influence on BehaviorTreatment of Major DepressionNeural and Behavioral Psychology Studies

The role of the brain reward system in depression

Naranjo, Claudio A., Tremblay, Lescia K., Busto, Usoa E.·2001·Progress in Neuro-Psychopharmacology and Biological Psychiatry

DOI 10.1016/s0278-5846(01)00156-7

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Abstract

The goal of this review is to familiarize the reader about the potential involvement of the brain reward system (BRS) in symptoms of Major Depressive Disorder (MDD). The authors introduce a novel approach to study the pathophysiology of MDD that includes pharmacological probing of BRS pathways (e.g. d-amphetamine, hydromorphone) together with an elicited and measurable behavioral component (e.g. pleasant effects, increased energy, altered cognition). To this date, the major focus of MDD pathophysiology studies has been to characterize biological differences between healthy subjects and depressed patients such as alteration in the monoaminergic and endocrine systems. The relative importance of the various biological changes has not been elucidated, that is, linking these with specific behavioral manifestations in MDD have rarely been attempted. One core symptom of MDD is a decreased experience of pleasure or interest in previously enjoyed activities (i.e. anhedonia) such as work or hobbies, and is accompanied by decreased motivation or drive. The BRS consists of the neural pathways involved in eliciting rewarding experiences in animals and humans. The hypothesis is that altered BRS function may be an underlying brain mechanism of the loss of pleasure/interest experienced in MDD, and will be manifested through an altered response to a BRS probe. The authors have examined BRS function in MDD by introducing a pharmacological probe (i.e. d-amphetamine/d-amph). Amphetamine is defined as a probe due to its ability to release dopamine within major components of the BRS (i.e. the mesocorticolimbic dopamine system.) In addition to the objective pharmacological effects (e.g. altered heart rate), BRS probes like d-amph elicit reliable and measurable behavior, that is, the hedonic effects. A review of the neurobiology of MDD, the BRS, the rationale for implicating the BRS in depressive symptoms, and preliminary data, are presented in this article.

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The Neural Correlates of Anhedonia in Major Depressive Disorder
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Neural Evidence for Enhanced Error Detection in Major Depressive Disorder
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Neurobiological mechanisms of anhedonia
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Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood
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Meta-analysis of reward processing in major depressive disorder reveals distinct abnormalities within the reward circuit
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Reinforcement learning in depression: a review of computational research
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The antidepressant effect of running is associated with increased hippocampal cell proliferation
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Why Don't You Try Harder? An Investigation of Effort Production in Major Depression
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The Psychopathology and Treatment of Bipolar Disorder
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Sex differences in the effects of two stress paradigms on dopaminergic neurotransmission
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The natural context of wellbeing: Ecological momentary assessment of the influence of nature and daylight on affect and stress for individuals with depression levels varying from none to clinical
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Dopamine D2-Like Receptors and the Antidepressant Response
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Transcranial magnetic stimulation induces increases in extracellular levels of dopamine and glutamate in the nucleus accumbens
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Antidepressant-like actions of DOV 21,947: a “triple” reuptake inhibitor
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Behavioral Alterations in Reward System Function
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Brain Systems Underlying Susceptibility to Helplessness and Depression
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Emotional sensitivity for motherhood: Late pregnancy is associated with enhanced accuracy to encode emotional faces
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Chronic treatment with fluoxetine up-regulates cellular BDNF mRNA expression in rat dopaminergic regions
Molteni, R., Calabrese, F., Bedogni, F., Tongiorgi, E., Fumagalli, F., Racagni, G., & Andrea Riva, M. (2006) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145705005766 · Cited by 132 · see citing works
Disruption to the development of maternal responsiveness? The impact of prenatal depression on mother–infant interactions
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Impact of frequency of internet use on development of brain structures and verbal intelligence: Longitudinal analyses
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Neural mechanisms of reinforcement learning in unmedicated patients with major depressive disorder
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Depressive symptoms in early pregnancy disrupt attentional processing of infant emotion
Pearson, R. M., Cooper, R. M., Penton‐Voak, I. S., Lightman, S. L., & Evans, J. (2009) · Psychological Medicine · doi:10.1017/s0033291709990961 · Cited by 128 · see citing works
The effects of tyrosine depletion in normal healthy volunteers: implications for unipolar depression
McLean, A., Rubinsztein, J. S., Robbins, T. W., & Sahakian, B. J. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1586-8 · Cited by 125 · see citing works
Anhedonia revisited: Is there a role for dopamine-targeting drugs for depression?
Argyropoulos, S. V., & Nutt, D. (2013) · Journal of Psychopharmacology · doi:10.1177/0269881113494104 · Cited by 122 · see citing works
Cognitive, Behavioral, and Affective Responses to Reward: Links with Hypomanic Symptoms
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Evaluation of reward processes in an animal model of depression
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The neural circuitry of reward and its relevance to psychiatric disorders
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Reward‐aversion circuitry in analgesia and pain: Implications for psychiatric disorders
Borsook, D., Becerra, L. R., Carlezon, W. A., Shaw, M. E., Renshaw, P. F., Elman, I., & Levine, J. D. (2006) · European Journal of Pain · doi:10.1016/j.ejpain.2005.12.005 · Cited by 122 · see citing works
Vitamin D and Pain: Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities
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Vitamin D and Autism Spectrum Disorder: A Literature Review
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Structural and functional models of depression: from sub‐types to substrates
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Acupuncture treatment modulates the corticostriatal reward circuitry in major depressive disorder
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Short- and Long-Term Functional Consequences of Fluoxetine Exposure During Adolescence in Male Rats
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Preclinical and Clinical Pharmacology of DOV 216,303, a “Triple” Reuptake Inhibitor
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NEURAL REACTIVITY TO REWARD AS A PREDICTOR OF COGNITIVE BEHAVIORAL THERAPY RESPONSE IN ANXIETY AND DEPRESSION
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Extracellular Signal-Regulated Kinase-2 within the Ventral Tegmental Area Regulates Responses to Stress
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Simultaneous detection of dopamine, ascorbic acid, and uric acid at electrochemically pretreated carbon nanotube biosensors
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The empirical status of melancholia: Implications for psychology
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The Reward Probability Index: Design and Validation of a Scale Measuring Access to Environmental Reward
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Serotonin transporter polymorphism mediates vulnerability to loss of incentive motivation following acute tryptophan depletion.
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‘The risks of playing it safe’: a prospective longitudinal study of response to reward in the adolescent offspring of depressed parents
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Emerging drugs for major depressive disorder
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The subjective and cognitive effects of acute phenylalanine and tyrosine depletion in patients recovered from depression
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The Interface of Oxytocin-Labeled Cells and Serotonin Transporter-Containing Fibers in the Primate Hypothalamus: A Substrate for SSRIs Therapeutic Effects?
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Oestrogen‐deficient female aromatase knockout (ArKO) mice exhibit ‘depressive‐like’ symptomatology
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Validation of an ELISA for urinary dopamine: applications in monitoring treatment of dopamine‐related disorders
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Prospect of a Dopamine Contribution in the Next Generation of Antidepressant Drugs: The Triple Reuptake Inhibitors
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Deficits in sustaining reward responses in subsyndromal and syndromal major depression
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Localization of white-matter lesions and effect of vascular risk factors in late-onset major depression
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Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals
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The Ups and Downs of Modelling Mood Disorders in Rodents
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Emotional dysfunction in Parkinson's disease.
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Retinoid-Mediated Regulation of Mood: Possible Cellular Mechanisms
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Emotional Dysfunction in Parkinson’s Disease
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Differentiating the abnormalities of social and monetary reward processing associated with depressive symptoms
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Antidepressant-Like Effect of D2/3 Receptor-, but not D4 Receptor-Activation in the Rat Forced Swim Test
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Programmed Acute Electrical Stimulation of Ventral Tegmental Area Alleviates Depressive-Like Behavior
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Brain reward system dysfunction in major depressive disorder: differential behavioural response to d-amphetamine and corresponding neuroanatomical substrates
Tremblay, L. K. (2002) · TSpace (University of Toronto)
Self-citation
Probing Brain Reward System Function in Major Depressive Disorder: Altered Response to Dextroamphetamine
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Self-citation
Is depression associated with dysfunction of the central reward system?
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This Month in Archives of General Psychiatry
(2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.5.407
Functional Neuroanatomical Substrates of Altered Reward Processing in Major Depressive Disorder Revealed by a Dopaminergic Probe
Tremblay, L. K., Naranjo, C. A., Graham, S. J., Herrmann, N., Mayberg, H. S., Hevenor, S., & Busto, U. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.11.1228 · Cited by 340 · see citing works
Self-citation

Authors: Naranjo, C. A., Tremblay, L. K., & Busto, U. E.
Affiliations: Sunnybrook Health Science Centre (CA)
Corresponding author: Naranjo, Claudio A.
Venue: Progress in Neuro-Psychopharmacology and Biological Psychiatry
Publisher: Elsevier BV
Published: 2001-05
Volume: 25
Issue: 4
Pages: 781-823
ISSN: 0278-5846 (ISSN-L)
DOI: 10.1016/s0278-5846(01)00156-7
OpenAlex: W2040295810
Cited by: 245
References: 271
Citations by year: 2025: 7 · 2024: 5 · 2023: 3 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 8 · 2014: 7 · 2013: 13 · 2012: 13
FWCI: 0.77
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: brain reward system, major depressive disorder, anhedonia, dopamine, mesocorticolimbic dopamine system, amphetamine challenge, hydromorphone, motivation, depression pathophysiology
MeSH terms: Amphetamine, Central Nervous System Stimulants, Animals, Brain, Brain Chemistry, Depressive Disorder, Humans, Reward

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The role of the brain reward system in depression

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