Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.2
3.9
Journals
Biomedicines
Special Issues
Dopamine Signaling Pathway in Health and Disease—2nd Edition
share announcement

Dopamine Signaling Pathway in Health and Disease—2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 14433

Special Issue Editors

Prof. Dr. Floriana Volpicelli

E-Mail Website
Guest Editor
Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131, Naples, Italy
Interests: synaptic plasticity; synaptic transmission; signaling pathways; regulation of gene expression
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Maria Concetta Miniaci

E-Mail Website
Guest Editor
Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80131, Naples, Italy
Interests: Neuromodulation; synaptic plasticity; learning and memory; neurodegeneration
Special Issues, Collections and Topics in MDPI journals
Dr. Luisa Speranza

E-Mail Website1 Website2
Guest Editor
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
Interests: neuronal plasticity and homeostasis; autophagy; protein synthesis; intellectual disability
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dopamine plays a pivotal role as a neurotransmitter, regulating numerous essential physiological functions within the central nervous system. These functions encompass motor behavior, affective and emotional states, reward and reinforcement behaviors, as well as various higher cognitive functions. The four primary dopaminergic pathways are the nigrostriatal, mesocortical, mesolimbic, and tuberoinfundibular pathways. Dysfunction in the dopaminergic transmission is recognized as a core alteration in several neurological and psychiatric disorders, including Parkinson’s disease, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD), and addiction. 

This Special Issue, titled "Dopamine Signaling Pathway in Health and Disease—2nd Edition", will feature a curated collection of original research papers and reviews. These contributions will explore the cellular and molecular mechanisms that underlie dopaminergic neuromodulation under physiological conditions, as well as in preclinical cellular and animal models of dopaminergic neurodegeneration. Additionally, the issue will examine innovative pharmacological approaches for addressing dopamine-related disorders.

Prof. Dr. Floriana Volpicelli
Prof. Dr. Maria Concetta Miniaci
Dr. Luisa Speranza
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. Biomedicines 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 2600 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

  • differentiation
  • disease modeling 
  • dopamine and drugs
  • gene expression
  • human stem cells
  • neuronal development
  • reprogramming
  • signaling pathways
  • neurodegeneration
  • neuromodulation

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (8 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

20 pages, 5298 KiB  
Article
SNX19 Interacts with Caveolin-1 and Flotillin-1 to Regulate D1R Endocytosis and Signaling
by Bibhas Amatya, Jacob Q. M. Polzin, Van A. M. Villar, Jiang Yang, Prasad Konkalmatt, Xiaoyan Wang, Raisha C. Cadme, Peng Xu, John J. Gildea, Santiago Cuevas, Ines Armando, Robin A. Felder, Pedro A. Jose and Hewang Lee
Biomedicines 2025, 13(2), 481; https://doi.org/10.3390/biomedicines13020481 - 15 Feb 2025
Viewed by 603
Abstract
Background: Sorting nexin 19 (SNX19) is important in the localization and trafficking of the dopamine D1 receptor (D1R) to lipid raft microdomains. However, the interaction between SNX19 and the lipid raft components caveolin-1 or flotillin-1 and, in particular, their roles [...] Read more.
Background: Sorting nexin 19 (SNX19) is important in the localization and trafficking of the dopamine D1 receptor (D1R) to lipid raft microdomains. However, the interaction between SNX19 and the lipid raft components caveolin-1 or flotillin-1 and, in particular, their roles in the cellular endocytosis and cell membrane trafficking of the D1R have not been determined. Methods: Caveolin-1 and flotillin-1 motifs were analyzed by in silico analysis; colocalization was observed by confocal immunofluorescence microscopy; protein-protein interaction was determined by co-immunoprecipitation. Results: In silico analysis revealed the presence of putative caveolin-1 and flotillin-1 binding motifs within SNX19. In mouse and human renal proximal tubule cells (RPTCs), SNX19 was localized mainly in lipid rafts. In mouse RPTCs transfected with wild-type (WT) Snx19, fenoldopam (FEN), a D1-like receptor agonist, increased the colocalization of SNX19 with caveolin-1 and flotillin-1. FEN also increased the co-immunoprecipitation of SNX19 with caveolin-1 and flotillin-1, effects that were prevented by SCH39166, a D1-like receptor antagonist. The FEN-mediated increase in the residence of SNX19 in lipid rafts and the colocalization of the D1R with caveolin-1 and flotilin-1 were attenuated by the deletion of a caveolin-1 (YHTVNRRYREF) (ΔCav1) or a flotillin-1 (EEGPGTETETGLPVS) (ΔFlot1) binding motif. The FEN-mediated increase in intracellular cAMP production was also impaired by the deletion of either the flotillin-1 or caveolin-1 binding motif. Nocodazole, a microtubule depolymerization inhibitor, interfered with the FEN-mediated increase in the colocalization between SNX19 and D1R. Conclusion: SNX19 contains caveolin-1 and flotillin-1 binding motifs, which play an important role in D1R endocytosis and signaling. Full article
(This article belongs to the Special Issue Dopamine Signaling Pathway in Health and Disease—2nd Edition)
►▼ Show Figures

Graphical abstract

15 pages, 1521 KiB  
Article
Disease-Associated Dopamine Receptor D2 Variants Exhibit Functional Consequences Depending on Different Heterotrimeric G-Protein Subunit Combinations
by Nele Niebrügge, Olga Trovato, Roman Praschberger and Andreas Lieb
Biomedicines 2025, 13(1), 46; https://doi.org/10.3390/biomedicines13010046 - 28 Dec 2024
Viewed by 1153
Abstract
Background: Dopamine receptors (DRs) are G-protein-coupled receptors (GPCRs) found in the central nervous system (CNS). DRs are essential for mediating various downstream signaling cascades and play a critical role in regulating the dopaminergic nigrostriatal pathway, which is involved in motor control. Recently, mutations [...] Read more.
Background: Dopamine receptors (DRs) are G-protein-coupled receptors (GPCRs) found in the central nervous system (CNS). DRs are essential for mediating various downstream signaling cascades and play a critical role in regulating the dopaminergic nigrostriatal pathway, which is involved in motor control. Recently, mutations in DRD2 (WT), p.Ile212Phe (I212F), and p.Met345Arg (M345R) have been associated with hyperkinetic movement disorders and shown to alter heterotrimeric G-protein complex signaling and β-arrestin recruitment. Methods: To conduct a detailed investigation of the I212F and M345R functional phenotypes, we used the TRansdUcer PATHway (TRUPATH) assay to study heterotrimeric G-protein recruitment and the Parallel Receptorome Expression and Screening via Transcriptional Output (PRESTO-Tango) assay to evaluate transcriptional activation following arrestin translocation for β-arrestin recruitment. Results: In our study, we could confirm the reported mutant’s loss-of-function phenotype in β-arrestin 2 recruitment (reduced agonist potency and decreased maximal signaling efficacy in comparison to the WT). However, a detailed analysis of basal/constitutive activity also revealed a gain-of-function phenotype for mutant M345R. For a more comprehensive investigation of heterotrimeric G-protein complex signaling, we investigated the impact of WT mutants in combination with (i) a specifically suggested assay, and (ii) the most abundantly expressed heterotrimeric G-protein complex combinations in WT receptor-enriched regions. We were able to confirm the reported gain-of-function phenotype by Rodriguez-Contreras et al. and extend it by the use of the most abundant heterotrimeric G-protein subunits, GαoA and Gαi1, β1 and β2, and γ3 and γ7, in mouse and human basal ganglia. Conclusions: Although our results indicate that the interaction of the two variants with the most highly expressed heterotrimeric G-protein complex subunit combinations also results in a gain-of-function phenotype, they also clearly demonstrate that the phenotype can be significantly altered, dependent on heterotrimeric G-protein complex expression. Full article
(This article belongs to the Special Issue Dopamine Signaling Pathway in Health and Disease—2nd Edition)
►▼ Show Figures

Figure 1

22 pages, 4034 KiB  
Article
Dopamine-Sensitive Anterior Cingulate Cortical Glucose-Monitoring Neurons as Potential Therapeutic Targets for Gustatory and Other Behavior Alterations
by Edina Hormay, Bettina László, István Szabó, Kitti Mintál, Beáta Berta, Tamás Ollmann, László Péczely, Bernadett Nagy, Attila Tóth, Kristóf László, László Lénárd and Zoltán Karádi
Biomedicines 2024, 12(12), 2803; https://doi.org/10.3390/biomedicines12122803 - 10 Dec 2024
Viewed by 822
Abstract
Background: The anterior cingulate cortex (ACC) is known for its involvement in various regulatory functions, including in the central control of feeding. Activation of local elements of the central glucose-monitoring (GM) neuronal network appears to be indispensable in these regulatory processes. Destruction [...] Read more.
Background: The anterior cingulate cortex (ACC) is known for its involvement in various regulatory functions, including in the central control of feeding. Activation of local elements of the central glucose-monitoring (GM) neuronal network appears to be indispensable in these regulatory processes. Destruction of these type 2 glucose transporter protein (GLUT2)-equipped chemosensory cells results in multiple feeding-associated functional alterations. Methods: In order to examine this complex symptomatology, (1) dopamine sensitivity was studied in laboratory rats by means of the single-neuron-recording multibarreled microelectrophoretic technique, and (2) after local bilateral microinjection of the selective type 2 glucose transporter proteindemolishing streptozotocin (STZ), open-field, elevated plus maze, two-bottle and taste reactivity tests were performed. Results: A high proportion of the anterior cingulate cortical neurons changed their firing rate in response to microelectrophoretic administration of D-glucose, thus verifying them as local elements of the central glucose-monitoring network. Approximately 20% of the recorded cells displayed activity changes in response to microelectrophoretic application of dopamine, and almost 50% of the glucose-monitoring units here proved to be dopamine-sensitive. Moreover, taste stimulation experiments revealed even higher (80%) gustatory sensitivity dominance of these chemosensory cells. The anterior cingulate cortical STZ microinjections resulted in extensive behavioral and taste-associated functional deficits. Conclusions: The present findings provided evidence for the selective loss of glucose-monitoring neurons in the anterior cingulate cortex leading to motivated behavioral and gustatory alterations. This complex dataset also underlines the varied significance of the type 2 glucose transporter protein-equipped, dopamine-sensitive glucose-monitoring neurons as potential therapeutic targets. These units appear to be indispensable in adaptive control mechanisms of the homeostatic–motivational–emotional–cognitive balance for the overall well-being of the organism. Full article
(This article belongs to the Special Issue Dopamine Signaling Pathway in Health and Disease—2nd Edition)
►▼ Show Figures

Figure 1

18 pages, 7734 KiB  
Article
Direct Pathway Neurons in the Mouse Ventral Striatum Are Active During Goal-Directed Action but Not Reward Consumption During Operant Conditioning
by Stefano Cataldi, Clay Lacefield, N Shashaank and David Sulzer
Biomedicines 2024, 12(12), 2755; https://doi.org/10.3390/biomedicines12122755 - 2 Dec 2024
Viewed by 1482
Abstract
Background/Objectives: Learning is classically modeled to consist of an acquisition period followed by a mastery period when the skill no longer requires conscious control and becomes automatic. Dopamine neurons projecting to the ventral striatum (VS) produce a teaching signal that shifts from responding [...] Read more.
Background/Objectives: Learning is classically modeled to consist of an acquisition period followed by a mastery period when the skill no longer requires conscious control and becomes automatic. Dopamine neurons projecting to the ventral striatum (VS) produce a teaching signal that shifts from responding to rewarding or aversive events to anticipating cues, thus facilitating learning. However, the role of the dopamine-receptive neurons in the ventral striatum, particularly in encoding decision-making processes, remains less understood. Methods: Here, we introduce an operant conditioning paradigm using open-source microcontrollers to train mice in three sequential learning phases. Phase I employs classical conditioning, associating a 5 s sound cue (CS) with a sucrose–water reward. In Phase II, the CS is replaced by a lever press as the requirement for reward delivery, marking an operant conditioning stage. Phase III combines these elements, requiring mice to press the lever during the CS to obtain the reward. We recorded calcium signals from direct pathway spiny projection neurons (dSPNs) in the VS throughout the three phases of training. Results: We find that dSPNs are specifically engaged when the mouse makes a decision to perform a reward-seeking action in response to a CS but are largely inactive during actions taken outside the CS. Conclusions: These findings suggest that direct pathway neurons in the VS contribute to decision-making in learned action–outcome associations, indicating a specialized role in initiating operant behaviors. Full article
(This article belongs to the Special Issue Dopamine Signaling Pathway in Health and Disease—2nd Edition)
►▼ Show Figures

Graphical abstract

18 pages, 3851 KiB  
Article
Possible Potentiating Effects of Combined Administration of Alcohol, Caffeine, and Nicotine on In Vivo Dopamine Release in Addiction-Related Circuits Within the CNS of Rats
by Carmen Costas-Ferreira, Martiño Barreiro-Chapela, Rafael Durán and Lilian R. Ferreira Faro
Biomedicines 2024, 12(11), 2591; https://doi.org/10.3390/biomedicines12112591 - 13 Nov 2024
Viewed by 1548
Abstract
Background: Studies that assess the effects of the interaction of psychoactive substances on dopamine release, the key neurotransmitter in the neurochemical and behavioral effects related to drug consumption, are crucial to understand both their roles and the dysfunctions they produce in the central [...] Read more.
Background: Studies that assess the effects of the interaction of psychoactive substances on dopamine release, the key neurotransmitter in the neurochemical and behavioral effects related to drug consumption, are crucial to understand both their roles and the dysfunctions they produce in the central nervous system. Objective: We evaluated the effects of individual and combined administration of the three most widely consumed psychoactive substances in the world, ethanol, caffeine, and nicotine, on dopaminergic neurotransmission in three brain regions of rats related to addiction: the prefrontal cortex (PFC), the nucleus accumbens (NAcc), and the dorsal striatum. Methods: The dopamine levels were measured in vivo by cerebral microdialysis associated with HPLC-ED. Results: We observed that local administration of a single concentration of caffeine (5 mM) or nicotine (5 mM) significantly increased the dopamine levels in all three areas studied, while ethanol (300 mM) increased them in the NAcc and striatum. Perfusion of nicotine + caffeine produced a synergistic effect in both the NAcc and striatum, with increases in the in vivo dopamine release greater than the sum of the effects of both substances. When administering the combination of nicotine + caffeine + ethanol, we observed an additive effect in the NAcc, while in the PFC we observed a synergistic effect. Conclusions: Our results support the stimulating effects of caffeine, nicotine, and ethanol on the brain reward system. In addition, we also observed that the administration of different mixtures of these substances produces synergistic and additive effects on the release of dopamine in the mesocortical and nigrostriatal systems. Full article
(This article belongs to the Special Issue Dopamine Signaling Pathway in Health and Disease—2nd Edition)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

34 pages, 1692 KiB  
Review
Enduring Neurobiological Consequences of Early-Life Stress: Insights from Rodent Behavioral Paradigms
by Luisa Speranza, Kardelen Dalim Filiz, Pellegrino Lippiello, Maria Grazia Ferraro, Silvia Pascarella, Maria Concetta Miniaci and Floriana Volpicelli
Biomedicines 2024, 12(9), 1978; https://doi.org/10.3390/biomedicines12091978 - 2 Sep 2024
Cited by 7 | Viewed by 4749
Abstract
Stress profoundly affects physical and mental health, particularly when experienced early in life. Early-life stress (ELS) encompasses adverse childhood experiences such as abuse, neglect, violence, or chronic poverty. These stressors can induce long-lasting changes in brain structure and function, impacting areas involved in [...] Read more.
Stress profoundly affects physical and mental health, particularly when experienced early in life. Early-life stress (ELS) encompasses adverse childhood experiences such as abuse, neglect, violence, or chronic poverty. These stressors can induce long-lasting changes in brain structure and function, impacting areas involved in emotion regulation, cognition, and stress response. Consequently, individuals exposed to high levels of ELS are at an increased risk for mental health disorders like depression, anxiety, and post-traumatic stress disorders, as well as physical health issues, including metabolic disorders, cardiovascular disease, and cancer. This review explores the biological and psychological consequences of early-life adversity paradigms in rodents, such as maternal separation or deprivation and limited bedding or nesting. The study of these experimental models have revealed that the organism’s response to ELS is complex, involving genetic and epigenetic mechanisms, and is associated with the dysregulation of physiological systems like the nervous, neuroendocrine, and immune systems, in a sex-dependent fashion. Understanding the impact of ELS is crucial for developing effective interventions and preventive strategies in humans exposed to stressful or traumatic experiences in childhood. Full article
(This article belongs to the Special Issue Dopamine Signaling Pathway in Health and Disease—2nd Edition)
►▼ Show Figures

Figure 1

28 pages, 6931 KiB  
Review
BDNF-Regulated Modulation of Striatal Circuits and Implications for Parkinson’s Disease and Dystonia
by Daniel Wolf, Maurilyn Ayon-Olivas and Michael Sendtner
Biomedicines 2024, 12(8), 1761; https://doi.org/10.3390/biomedicines12081761 - 5 Aug 2024
Cited by 2 | Viewed by 2040
Abstract
Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival, and plasticity. BDNF is necessary for neuronal and functional maintenance in the striatum and the substantia nigra, both structures involved in the pathogenesis of Parkinson’s Disease (PD). Depletion of [...] Read more.
Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival, and plasticity. BDNF is necessary for neuronal and functional maintenance in the striatum and the substantia nigra, both structures involved in the pathogenesis of Parkinson’s Disease (PD). Depletion of BDNF leads to striatal degeneration and defects in the dendritic arborization of striatal neurons. Activation of tropomyosin receptor kinase B (TrkB) by BDNF is necessary for the induction of long-term potentiation (LTP), a form of synaptic plasticity, in the hippocampus and striatum. PD is characterized by the degeneration of nigrostriatal neurons and altered striatal plasticity has been implicated in the pathophysiology of PD motor symptoms, leading to imbalances in the basal ganglia motor pathways. Given its essential role in promoting neuronal survival and meditating synaptic plasticity in the motor system, BDNF might have an important impact on the pathophysiology of neurodegenerative diseases, such as PD. In this review, we focus on the role of BDNF in corticostriatal plasticity in movement disorders, including PD and dystonia. We discuss the mechanisms of how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Evidence for alterations of BDNF and TrkB in PD patients and animal models are reviewed, and the potential of BDNF to act as a therapeutic agent is highlighted. Advancing our understanding of these mechanisms could pave the way toward innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases. Full article
(This article belongs to the Special Issue Dopamine Signaling Pathway in Health and Disease—2nd Edition)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

12 pages, 996 KiB  
Systematic Review
The Role of Dopamine in Gastric Cancer—A Systematic Review of the Pathogenesis Phenomena Developments
by Radu-Cristian Cimpeanu, Dragoș Fortofoiu, Elena Sandu, Ioana-Gabriela Dragne, Mariana-Emilia Caragea, Roxana-Ioana Dumitriu-Stan, Bianca-Margareta Salmen, Lidia Boldeanu, Delia Viola Reurean-Pintilei and Cristin-Constantin Vere
Biomedicines 2024, 12(12), 2786; https://doi.org/10.3390/biomedicines12122786 - 7 Dec 2024
Viewed by 973
Abstract
Background: In the last few decades, it has been emphasized that dopamine, a well-known neurotransmitter with multiple roles in central nervous system, is also implicated in the activity of peripheral tissues and organs, more specifically influencing the gastrointestinal system (GI). Methods: We registered [...] Read more.
Background: In the last few decades, it has been emphasized that dopamine, a well-known neurotransmitter with multiple roles in central nervous system, is also implicated in the activity of peripheral tissues and organs, more specifically influencing the gastrointestinal system (GI). Methods: We registered a protocol under the CRD42024547935 identifier in the Prospero register of systematic reviews. Furthermore, using the Population, Intervention, Comparison, Outcome, and Study Design strategy to guide our study rationale, and under the Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations, we conducted a qualitative systematic literature search based on the PubMed, Scopus, and Web of Science databases using the “gastric cancers AND dopamine” search criteria. We obtained 68 articles from PubMed, 142 articles from Scopus, and 99 articles from the Web of Science database. Results: Within gastric cancer biology, dopamine has notable effects on STAT-3 and DARPP-32. STAT-3, a transcription factor involved in cellular proliferation and invasion, plays a significant role in cancer progression. Conclusions: Understanding the roles of dopamine in cancer, beyond aspects such as cancer cell invasion, immune response modulation, or tumor growth, could guide the development of new cancer therapies by modulating its pathways, especially the DARPP-32/CXCR4/CXCL-12 complex axis, in order to improve the morbidity and mortality caused by this type of cancer. Full article
(This article belongs to the Special Issue Dopamine Signaling Pathway in Health and Disease—2nd Edition)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-8
Back to TopTop