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Brain Sciences
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The Role of Dopamine in Neural Circuits
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The Role of Dopamine in Neural Circuits

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (9 February 2022) | Viewed by 31751

Special Issue Editors

Dr. Suelen Boschen

E-Mail Website
Guest Editor
Mayo Clinic, Rochester, NY, USA
Interests: pathophysiology mechanisms of neurodegenerative disorders; Parkinson's and Alzheimer's diseases; neuropsychological disorders; schizophrenia; depression
Dr. Paolo D'Aquila

E-Mail Website
Guest Editor
Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, Italy
Interests: dopamine; dopamine receptor; ingestion; licking microstructure; motivation; reward; behavioral activation; antidepressant drugs; depression model
Special Issues, Collections and Topics in MDPI journals
Dr. Deranda Lester

E-Mail Website
Guest Editor
Psychology Department, University of Memphis, 400 Innovation Drive Room 202, Memphis, TN 38152, USA
Interests: behavioral neuroscience; addiction; reward; anxiety; ADHD; dopamine; electrochemistry; oxytocin

Special Issue Information

Dear Colleagues,

The classic anatomical separation of the midbrain dopaminergic pathways into four distinct circuits was defined over four decades ago and remains valid today. The multiple subsets of the midbrain dopaminergic neurons transmit distinct functional signals with different roles in the brain. For example, dopaminergic neurons in the ventral tegmental area (VTA) project to the prefrontal cortex via the mesocortical and to the nucleus accumbens via the mesolimbic pathways, and play a role in reward and motivation. The dopamine neurons in the substantia nigra pars compacta, that project to the striatum, form the nigrostriatal pathway and are associated with the control of motor function and procedural learning. Lastly, in the tuberoinfundibular pathway, dopaminergic neurons in the hypothalamus project to the pituitary gland and regulate the secretion of prolactin. Over the past decade, however, our understanding of the midbrain dopaminergic circuitry has changed from a simple anatomo-functional classification to a more intricately organized complex of interdigitated dopamine neuron subtypes that express different molecular features, with specific signaling, functional properties, and a diverse behavioral outcome. A comprehensive review of the organization and dynamic characteristics of the dopaminergic circuitry is essential to understand its physiological role in multiple biological functions, as well as its involvement in neurological and psychiatric diseases. This research topic focuses on presenting recent advances on the role of dopamine in motivation, drug addiction, motor control, and reward and aversive processing, while providing a link to the associated brain circuitry and its relevance to neuropsychiatric function and potential therapies.

Dr. Suelen Boschen
Dr. Paolo D'Aquila
Dr. Deranda Lester
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • The Role of Dopamine in Neural Circuits

    dopamine
  • motivation
  • reward
  • aversion
  • learning
  • motor behavior
  • dopamine receptors

Published Papers (8 papers)

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Editorial

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3 pages, 163 KiB  
Editorial
A Special Issue on the Roles of Dopamine in Neural Circuits, Genetics, and Behavior
by Suelen L. Boschen, Paolo S. D’Aquila and Deranda B. Lester
Brain Sci. 2024, 14(1), 20; https://doi.org/10.3390/brainsci14010020 - 23 Dec 2023
Cited by 1 | Viewed by 859
Abstract
Over the past 80 years, research on dopamine has undergone significant evolution, reshaping our understanding of its roles in the brain and the body [...] Full article
(This article belongs to the Special Issue The Role of Dopamine in Neural Circuits)

Research

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11 pages, 506 KiB  
Article
Expression of Dopamine-Related Genes in Four Human Brain Regions
by Ansley Grimes Stanfill and Xueyuan Cao
Brain Sci. 2020, 10(8), 567; https://doi.org/10.3390/brainsci10080567 - 18 Aug 2020
Cited by 6 | Viewed by 3333
Abstract
A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes [...] Read more.
A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions. Full article
(This article belongs to the Special Issue The Role of Dopamine in Neural Circuits)
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10 pages, 749 KiB  
Communication
Transient Administration of Dopaminergic Precursor Causes Inheritable Overfeeding Behavior in Young Drosophila melanogaster Adults
by Thiago C. Moulin, Federico Ferro, Samuel Berkins, Angela Hoyer, Michael J. Williams and Helgi B. Schiöth
Brain Sci. 2020, 10(8), 487; https://doi.org/10.3390/brainsci10080487 - 28 Jul 2020
Cited by 6 | Viewed by 3032
Abstract
Imbalances in dopaminergic signaling during development have been indicated as part of the underlying neurobiology of several psychiatric illnesses, including schizophrenia, major depression, bipolar disorder, and food addiction. Yet, how transient manipulation of dopaminergic signaling influences long-lasting behavioral consequences, or if these modifications [...] Read more.
Imbalances in dopaminergic signaling during development have been indicated as part of the underlying neurobiology of several psychiatric illnesses, including schizophrenia, major depression, bipolar disorder, and food addiction. Yet, how transient manipulation of dopaminergic signaling influences long-lasting behavioral consequences, or if these modifications can induce inheritable traits, it is still not understood. In this study, we used the Drosophila melanogaster model to test if transient pharmacological activation of the dopaminergic system leads to modulations of feeding and locomotion in adult flies. We observed that transient administration of a dopaminergic precursor, levodopa, at 6 h, 3 days or 5 days post-eclosion, induced overfeeding behavior, while we did not find significant effects on locomotion. Moreover, this phenotype was inherited by the offspring of flies treated 6 h or 3 days post-eclosion, but not the offspring of those treated 5 days post-eclosion. These results indicate that transient alterations in dopaminergic signaling can produce behavioral alterations in adults, which can then be carried to descendants. These findings provide novel insights into the conditions in which environmental factors can produce transgenerational eating disorders. Full article
(This article belongs to the Special Issue The Role of Dopamine in Neural Circuits)
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11 pages, 632 KiB  
Article
Contribution of Dopamine Transporter Gene Methylation Status to Cannabis Dependency
by Anna Grzywacz, Wojciech Barczak, Jolanta Chmielowiec, Krzysztof Chmielowiec, Aleksandra Suchanecka, Grzegorz Trybek, Jolanta Masiak, Paweł Jagielski, Katarzyna Grocholewicz and Blazej Rubiś
Brain Sci. 2020, 10(6), 400; https://doi.org/10.3390/brainsci10060400 - 23 Jun 2020
Cited by 15 | Viewed by 3036
Abstract
The susceptibility to cannabis dependency results from the influence of numerous factors such as social, genetic, as well as epigenetic factors. Many studies have attempted to discover a molecular basis for this disease. However, our study aimed at evaluating the connection between altered [...] Read more.
The susceptibility to cannabis dependency results from the influence of numerous factors such as social, genetic, as well as epigenetic factors. Many studies have attempted to discover a molecular basis for this disease. However, our study aimed at evaluating the connection between altered methylation of the dopamine transporter gene (DAT1) promoter CpG sites and cannabis dependency. In the cases of some DNA sequences, including the DAT1 gene region, their methylation status in blood cells may reflect a systemic modulation in the whole organism. Consequently, we isolated the DNA from the peripheral blood cells from a group of 201 cannabis-dependent patients and 285 controls who were healthy volunteers and who were matched for age and sex. The DNA was subjected to bisulfite conversion and sequencing. Our analysis revealed no statistical differences in the general methylation status of the DAT1 gene promoter CpG island between the patients and controls. Yet, the analysis of individual CpG sites where methylation occurred indicated significant differences. These sites are known to be bound by transcription factors (e.g., SP1, p53, PAX5, or GR), which, apart from other functions, were shown to play a role in the development of the nervous system. Therefore, DAT1 gene promoter methylation studies may provide important insight into the mechanism of cannabis dependency. Full article
(This article belongs to the Special Issue The Role of Dopamine in Neural Circuits)
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12 pages, 451 KiB  
Article
Dopamine Receptor DRD2 Gene rs1076560, Personality Traits and Anxiety in the Polysubstance Use Disorder
by Aleksandra Suchanecka, Jolanta Chmielowiec, Krzysztof Chmielowiec, Jolanta Masiak, Olimpia Sipak-Szmigiel, Mariusz Sznabowicz, Wojciech Czarny, Monika Michałowska-Sawczyn, Grzegorz Trybek and Anna Grzywacz
Brain Sci. 2020, 10(5), 262; https://doi.org/10.3390/brainsci10050262 - 30 Apr 2020
Cited by 10 | Viewed by 3108
Abstract
Development of an addiction is conditioned by many factors. The dopaminergic system has been shown to be the key element in this process. In this paper, we analyzed the influence of dopamine receptor 2 polymorphism rs1076560 in two groups—polysubstance-dependent male patients (n = [...] Read more.
Development of an addiction is conditioned by many factors. The dopaminergic system has been shown to be the key element in this process. In this paper, we analyzed the influence of dopamine receptor 2 polymorphism rs1076560 in two groups—polysubstance-dependent male patients (n = 299) and the controls matched for age (n = 301). In both groups, we applied the same questionnaires for testing—Mini-international neuropsychiatric interview, the NEO Five-Factor Inventory, and the State–Trait Anxiety Inventory. The real-time PCR method was used for genotyping. When we compared the controls with the case group subjects, we observed significantly higher scores in the second group on both the state and trait scales of anxiety, as well as on the Neuroticism and Openness scales of the NEO-FFI; and lower scores on the scales of Extraversion and Agreeability of the NEO-FFI. The model 2 × 3 factorial ANOVA of the addicted subjects and controls was performed, and the DRD2 rs1076560 variant interaction was found for the anxiety state and trait scales, and for the NEO-FFI Neuroticism scale. The observed associations allow noticing that analysis of psychological factors in combination with genetic data opens new possibilities in addiction research. Full article
(This article belongs to the Special Issue The Role of Dopamine in Neural Circuits)
18 pages, 5127 KiB  
Article
Transient Chemogenetic Inhibition of D1-MSNs in the Dorsal Striatum Enhances Methamphetamine Self-Administration
by Robert J. Oliver, Dvijen C. Purohit, Khush M. Kharidia and Chitra D. Mandyam
Brain Sci. 2019, 9(11), 330; https://doi.org/10.3390/brainsci9110330 - 19 Nov 2019
Cited by 8 | Viewed by 3798
Abstract
The dorsal striatum is important for the development of drug addiction; however, the role of dopamine D1 receptor (D1R) expressing medium-sized spiny striatonigral (direct pathway) neurons (D1-MSNs) in regulating excessive methamphetamine intake remains elusive. Here we seek to determine if modulating D1-MSNs in [...] Read more.
The dorsal striatum is important for the development of drug addiction; however, the role of dopamine D1 receptor (D1R) expressing medium-sized spiny striatonigral (direct pathway) neurons (D1-MSNs) in regulating excessive methamphetamine intake remains elusive. Here we seek to determine if modulating D1-MSNs in the dorsal striatum alters methamphetamine self-administration in animals that have demonstrated escalation of self-administration. A viral vector-mediated approach was used to induce expression of the inhibitory (Gi coupled-hM4D) or stimulatory (Gs coupled-rM3D) designer receptors exclusively activated by designer drugs (DREADDs) engineered to specifically respond to the exogenous ligand clozapine-N-oxide (CNO) selectively in D1-MSNs in the dorsal striatum. CNO in animals expressing hM4D increased responding for methamphetamine compared to vehicle in a within subject treatment paradigm. CNO in animals that did not express DREADDs (DREADD naïve-CNO) or expressed rM3D did not alter responding for methamphetamine, demonstrating specificity for hM4D-CNO interaction in increasing self-administration. Postmortem tissue analysis reveals that hM4D-CNO animals had reduced Fos immunoreactivity in the dorsal striatum compared to rM3D-CNO animals and DREADD naïve-CNO animals. Cellular mechanisms in the dorsal striatum in hM4D-CNO animals reveal enhanced expression of D1R and Ca2+/calmodulin-dependent kinase II (CaMKII). Conversely, rM3D-CNO animals had enhanced activity of extracellular signal-regulated kinase (Erk1/2) and Akt in the dorsal striatum, supporting rM3D-CNO interaction in these animals compared with drug naïve controls, DREADD naïve-CNO and hM4D-CNO animals. Our studies indicate that transient inhibition of D1-MSNs-mediated strengthening of methamphetamine addiction-like behavior is associated with cellular adaptations that support dysfunctional dopamine signaling in the dorsal striatum. Full article
(This article belongs to the Special Issue The Role of Dopamine in Neural Circuits)
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Review

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14 pages, 799 KiB  
Review
Regulation of Voluntary Physical Activity Behavior: A Review of Evidence Involving Dopaminergic Pathways in the Brain
by Anaissa Ruiz-Tejada, Janet Neisewander and Christos S. Katsanos
Brain Sci. 2022, 12(3), 333; https://doi.org/10.3390/brainsci12030333 - 01 Mar 2022
Cited by 11 | Viewed by 10638
Abstract
Physical activity leads to well-established health benefits. Current efforts to enhance physical activity have targeted mainly socioeconomic factors. However, despite these efforts, only a small number of adults engage in regular physical activity to the point of meeting current recommendations. Evidence collected in [...] Read more.
Physical activity leads to well-established health benefits. Current efforts to enhance physical activity have targeted mainly socioeconomic factors. However, despite these efforts, only a small number of adults engage in regular physical activity to the point of meeting current recommendations. Evidence collected in rodent models and humans establish a strong central nervous system component that regulates physical activity behavior. In particular, dopaminergic pathways in the central nervous system are among the best-characterized biological mechanisms to date with respect to regulating reward, motivation, and habit formation, which are critical for establishing regular physical activity. Herein, we discuss evidence for a role of brain dopamine in the regulation of voluntary physical activity behavior based on selective breeding and pharmacological studies in rodents, as well as genetic studies in both rodents and humans. While these studies establish a role of dopamine and associated mechanisms in the brain in the regulation of voluntary physical activity behavior, there is clearly need for more research on the underlying biology involved in motivation for physical activity and the formation of a physical activity habit. Such knowledge at the basic science level may ultimately be translated into better strategies to enhance physical activity levels within the society. Full article
(This article belongs to the Special Issue The Role of Dopamine in Neural Circuits)
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11 pages, 432 KiB  
Review
Role of Stress-Related Dopamine Transmission in Building and Maintaining a Protective Cognitive Reserve
by Simona Cabib, Claudio Latagliata and Cristina Orsini
Brain Sci. 2022, 12(2), 246; https://doi.org/10.3390/brainsci12020246 - 11 Feb 2022
Cited by 6 | Viewed by 2070
Abstract
This short review presents the hypothesis that stress-dependent dopamine (DA) transmission contributes to developing and maintaining the brain network supporting a cognitive reserve. Research has shown that people with a greater cognitive reserve are better able to avoid symptoms of degenerative brain changes. [...] Read more.
This short review presents the hypothesis that stress-dependent dopamine (DA) transmission contributes to developing and maintaining the brain network supporting a cognitive reserve. Research has shown that people with a greater cognitive reserve are better able to avoid symptoms of degenerative brain changes. The paper will review evidence that: (1) successful adaptation to stressors involves development and stabilization of effective but flexible coping strategies; (2) this process requires dynamic reorganization of functional networks in the adult brain; (3) DA transmission is amongst the principal mediators of this process; (4) age- and disease-dependent cognitive impairment is associated with dysfunctional connectivity both between and within these same networks as well as with reduced DA transmission. Full article
(This article belongs to the Special Issue The Role of Dopamine in Neural Circuits)
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