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Role of Dopamine in Health and Disease: Biological Aspect 2.0
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Role of Dopamine in Health and Disease: Biological Aspect 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 12355

Special Issue Editors

Dr. Anna Grzywacz

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Guest Editor
Independent Laboratory of Health Promotion, Department of Psychiatry, Pomeranian Medical University in Szczecin, 11 Chlapowskiego St., 70-204 Szczecin, Poland
Interests: clinic of psychiatry; addiction; genetics; personality traits
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jolanta Masiak

E-Mail Website
Guest Editor
Neurophysiological Independent Unit, Department of Psychiatry, Medical University of Lublin, 20-093 Lublin, Poland
Interests: clinical psychiatry; neurophysiology; reward system; dopamine; addictions; sport
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The dopaminergic system controls several vital central and peripheral nervous system functions, among others cognition, reward behaviors, processing of aversive experiences, and control of movement. Alterations of dopaminergic neurotransmission are involved in the pathogenesis mental of neurodegenerative disorders. The special issue with the leading topic of dopamine is an excellent opportunity for researchers, who deal with it, to share their knowledge. The major topic is dopamine in health and disease, but it can be presented from a different perspective—including basic, associative, genetic, and epigenetic research studies. We invite you to publish your papers within these subject areas: dopamine in addictions; dopamine in sports; dopamine in neurological diseases; dopamine as a neurotransmitter of happiness.

Dr. Anna Grzywacz
Prof. Dr. Jolanta Masiak
Guest Editors

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Keywords

  • dopamine
  • addiction
  • neurophysiology
  • dopaminergic system
  • neurotransmitter

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Published Papers (7 papers)

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Research

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28 pages, 5439 KiB  
Article
Initial Molecular Mechanisms of the Pathogenesis of Parkinson’s Disease in a Mouse Neurotoxic Model of the Earliest Preclinical Stage of This Disease
by Anna Kolacheva, Ekaterina Pavlova, Alyona Bannikova, Vsevolod Bogdanov and Michael Ugrumov
Int. J. Mol. Sci. 2024, 25(2), 1354; https://doi.org/10.3390/ijms25021354 - 22 Jan 2024
Cited by 1 | Viewed by 1459
Abstract
Studying the initial molecular mechanisms of the pathogenesis of Parkinson’s disease (PD), primarily in the nigrostriatal dopaminergic system, is one of the priorities in neurology. Of particular interest is elucidating these mechanisms in the preclinical stage of PD, which lasts decades before diagnosis [...] Read more.
Studying the initial molecular mechanisms of the pathogenesis of Parkinson’s disease (PD), primarily in the nigrostriatal dopaminergic system, is one of the priorities in neurology. Of particular interest is elucidating these mechanisms in the preclinical stage of PD, which lasts decades before diagnosis and is therefore not available for study in patients. Therefore, our main goal was to study the initial molecular mechanisms of the pathogenesis of PD in the striatum, the key center for dopamine regulation in motor function, in a mouse model of the earliest preclinical stage of PD, from 1 to 24 h after the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It was shown that the content of tyrosine hydroxylase (TH), the first enzyme in dopamine synthesis, does not change within 6 h after the administration of MPTP, but decreases after 24 h. In turn, TH activity increases after 1 h, decreases after 3 h, remains at the control level after 6 h, and decreases 24 h after the administration of MPTP. The concentration of dopamine in the striatum gradually decreases after MPTP administration, despite a decrease in its degradation. The identified initial molecular mechanisms of PD pathogenesis are considered as potential targets for the development of preventive neuroprotective treatment. Full article
(This article belongs to the Special Issue Role of Dopamine in Health and Disease: Biological Aspect 2.0)
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18 pages, 1113 KiB  
Article
Social Interaction in Adolescent Rats with Neonatal Ethanol Exposure: Impact of Sex and CE-123, a Selective Dopamine Reuptake Inhibitor
by Justyna Socha, Pawel Grochecki, Irena Smaga, Joanna Jastrzębska, Olga Wronikowska-Denysiuk, Marta Marszalek-Grabska, Tymoteusz Slowik, Robert Kotlinski, Małgorzata Filip, Gert Lubec and Jolanta H. Kotlinska
Int. J. Mol. Sci. 2024, 25(2), 1041; https://doi.org/10.3390/ijms25021041 - 15 Jan 2024
Cited by 3 | Viewed by 1556
Abstract
Children with fetal alcohol spectrum disorders (FASDs) demonstrate deficits in social functioning that contribute to early withdrawal from school and delinquency, as well as the development of anxiety and depression. Dopamine is involved in reward, motivation, and social behavior. Thus, we evaluated whether [...] Read more.
Children with fetal alcohol spectrum disorders (FASDs) demonstrate deficits in social functioning that contribute to early withdrawal from school and delinquency, as well as the development of anxiety and depression. Dopamine is involved in reward, motivation, and social behavior. Thus, we evaluated whether neonatal ethanol exposure (in an animal model of FASDs) has an impact on social recognition memory using the three-chamber social novelty discrimination test during early and middle adolescence in male and female rats, and whether the modafinil analog, the novel atypical dopamine reuptake inhibitor CE-123, can modify this effect. Our study shows that male and female rats neonatally exposed to ethanol exhibited sex- and age-dependent deficits in social novelty discrimination in early (male) and middle (female) adolescence. These deficits were specific to the social domain and not simply due to more general deficits in learning and memory because these animals did not exhibit changes in short-term recognition memory in the novel object recognition task. Furthermore, early-adolescent male rats that were neonatally exposed to ethanol did not show changes in the anxiety index but demonstrated an increase in locomotor activity. Chronic treatment with CE-123, however, prevented the appearance of these social deficits. In the hippocampus of adolescent rats, CE-123 increased BDNF and decreased its signal transduction TrkB receptor expression level in ethanol-exposed animals during development, suggesting an increase in neuroplasticity. Thus, selective dopamine reuptake inhibitors, such as CE-123, represent interesting drug candidates for the treatment of deficits in social behavior in adolescent individuals with FASDs. Full article
(This article belongs to the Special Issue Role of Dopamine in Health and Disease: Biological Aspect 2.0)
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12 pages, 709 KiB  
Article
Analysis of the Methylation Level of the DAT1 Dopamine Transporter Gene in Patients Addicted to Stimulants, Taking into Account an Analysis of Personality Traits
by Remigiusz Recław, Milena Lachowicz, Krzysztof Chmielowiec, Jolanta Chmielowiec, Aleksandra Strońska-Pluta, Michał Tomasz Kowalski, Bartosz Kudliński and Anna Grzywacz
Int. J. Mol. Sci. 2024, 25(1), 532; https://doi.org/10.3390/ijms25010532 - 30 Dec 2023
Viewed by 1275
Abstract
Drug addiction is a chronic biochemical drug use disorder that affects the human brain and behavior and leads to the uncontrolled use of legal or illicit drugs. It has been shown that three factors are involved in the development of addiction: genetic factors, [...] Read more.
Drug addiction is a chronic biochemical drug use disorder that affects the human brain and behavior and leads to the uncontrolled use of legal or illicit drugs. It has been shown that three factors are involved in the development of addiction: genetic factors, a diverse environment, and the effect of medication on gene expression. The comprehensive approach and holistic analysis of the problem are due to the multigenic and multifactorial nature of addiction. Dopamine, one of the major neurotransmitters in the brain, is believed to be the “culprit” that leads to a drug abuse-induced “high”. That is why, in our research, we focused mainly on the genes related to dopaminergic reuptake. In the present study, we chose methylation of the DAT1 dopamine transporter gene based on molecular reasons related to the dopaminergic theory of addiction. This study included two groups: 226 stimulant-dependent and 290 non-stimulant-dependent subjects. The analysis consisted of a case–control comparison of people addicted to psychostimulants compared to a control group of healthy and non-addicted people. There were differences in the levels of statistical significance between the groups. Our research shows lower methylation of islands 1, 9, and 14 in addicted people and greater methylation of islands 32 and 33. The difference in individual CpG methylation islands of the gene under study provides valuable information about the DNA methylation process in patients addicted to psychostimulants. Pearson’s linear correlation analysis in stimulant dependence showed a negative correlation between total methylation island levels and the NEO-FFI Neuroticism scale. In subjects with neuroticism, the methylation level was statistically significantly lower. Pearson’s linear correlation analysis of stimulant-dependent subjects showed a positive correlation between total methylation island levels and the NEO-FFI Openness scale and the NEO-FFI Conscientiousness scale. Full article
(This article belongs to the Special Issue Role of Dopamine in Health and Disease: Biological Aspect 2.0)
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19 pages, 2070 KiB  
Article
Repeated Cocaine Intake Differentially Impacts Striatal D2/3 Receptor Availability, Psychostimulant-Induced Dopamine Release, and Trait Behavioral Markers of Drug Abuse
by Ginna Urueña-Méndez, Andrea Dimiziani, Lidia Bellés, Raphaël Goutaudier and Nathalie Ginovart
Int. J. Mol. Sci. 2023, 24(17), 13238; https://doi.org/10.3390/ijms241713238 - 26 Aug 2023
Cited by 3 | Viewed by 1533
Abstract
Current research indicates that altered dopamine (DA) transmission in the striatum contributes to impulsivity and novelty-seeking, and it may mediate a link concerning a higher susceptibility to drug abuse. Whether increased susceptibility to drug abuse results from a hyperdopaminergic or hypodopaminergic state is [...] Read more.
Current research indicates that altered dopamine (DA) transmission in the striatum contributes to impulsivity and novelty-seeking, and it may mediate a link concerning a higher susceptibility to drug abuse. Whether increased susceptibility to drug abuse results from a hyperdopaminergic or hypodopaminergic state is still debated. Here, we simultaneously tracked changes in DA D2/3 receptor (D2/3R) availability and amphetamine-(AMPH)-induced DA release in relation to impulsivity and novelty-seeking prior to, and following, cocaine self-administration (SA) in Roman high- (RHA) and low- (RLA) avoidance rats. We found that high-impulsive/high novelty-seeking RHA rats exhibited lower D2/3R availabilities and higher AMPH-induced DA release in the striatum that predicted higher levels of cocaine intake compared with RLAs. Cocaine SA did not alter striatal D2/3R availability or impulsivity in RHA or RLA rats. Critically, cocaine exposure led to a baseline-dependent blunting of stimulated DA release in high-impulsive/high novelty-seeking RHA rats only, and to a baseline-dependent increase in novelty-seeking in low-impulsive/low novelty-seeking RLA rats only. Altogether, we propose that susceptibility to drug abuse results from an innate hyper-responsive DA system, promoting impulsive action and novelty-seeking, and producing stronger initial drug-reinforcing effects that contribute to the initiation and perpetuation of drug use. However, with repeated cocaine use, a tolerance to drug-induced striatal DA elevations develops, leading to a compensatory increase in drug consumption to overcome the reduced reward effects. Full article
(This article belongs to the Special Issue Role of Dopamine in Health and Disease: Biological Aspect 2.0)
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22 pages, 5106 KiB  
Article
Dopamine D3 Receptor Modulates Akt/mTOR and ERK1/2 Pathways Differently during the Reinstatement of Cocaine-Seeking Behavior Induced by Psychological versus Physiological Stress
by Aurelio Franco-García, Rocío Guerrero-Bautista, Juana María Hidalgo, Victoria Gómez-Murcia, María Victoria Milanés and Cristina Núñez
Int. J. Mol. Sci. 2023, 24(13), 11214; https://doi.org/10.3390/ijms241311214 - 7 Jul 2023
Viewed by 1410
Abstract
Stress triggers relapses in cocaine use that engage the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and dentate gyrus (DG). Preclinical research suggests that D3 receptor (D3R) antagonists may be a promising means to attenuate cocaine reward and relapse. As [...] Read more.
Stress triggers relapses in cocaine use that engage the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and dentate gyrus (DG). Preclinical research suggests that D3 receptor (D3R) antagonists may be a promising means to attenuate cocaine reward and relapse. As D3R regulates the activity of the Akt/mTOR and MEK/ERK1/2 pathways, we assessed the effects of SB-277011-A, a D3R antagonist, on the activity of these kinases during the reinstatement of cocaine-induced conditioned place preference (CPP) induced by psychological (restraint) and physiological (tail pinch) stress. Both stimuli reactivated an extinguished cocaine-CPP, but only restrained animals decreased their locomotor activity during reinstatement. Cocaine-seeking behavior reactivation was correlated with decreased p-Akt, p-mTOR, and p-ERK1/2 activation in both nuclei of restrained animals. While a D3R blockade prevented stress-induced CPP reinstatement and plasma corticosterone enhancement, SB-277011-A distinctly modulated Akt, mTOR, and ERK1/2 activation depending on the stressor and the dose used. Our data support the involvement of corticosterone in the SB-277011-A effects in restrained animals. Additionally, the ratios p-mTOR/mTOR and/or p-ERK1/2 /ERK1/2 in the BLA during stress-induced relapse seem to be related to the locomotor activity of animals receiving 48 mg/kg of the antagonist. Hence, our study indicates the D3R antagonist’s efficacy to prevent stress-induced relapses in drug use through distinct modulation of Akt/mTOR and MEK/ERK1/2 pathways in memory-processing nuclei. Full article
(This article belongs to the Special Issue Role of Dopamine in Health and Disease: Biological Aspect 2.0)
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Review

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25 pages, 1210 KiB  
Review
Systematic-Narrative Hybrid Literature Review: Crosstalk between Gastrointestinal Renin–Angiotensin and Dopaminergic Systems in the Regulation of Intestinal Permeability by Tight Junctions
by Nadia Khan, Magdalena Kurnik-Łucka, Gniewomir Latacz and Krzysztof Gil
Int. J. Mol. Sci. 2024, 25(10), 5566; https://doi.org/10.3390/ijms25105566 - 20 May 2024
Viewed by 1168
Abstract
In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin–angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) [...] Read more.
In the first part of this article, the role of intestinal epithelial tight junctions (TJs), together with gastrointestinal dopaminergic and renin–angiotensin systems, are narratively reviewed to provide sufficient background. In the second part, the current experimental data on the interplay between gastrointestinal (GI) dopaminergic and renin–angiotensin systems in the regulation of intestinal epithelial permeability are reviewed in a systematic manner using the PRISMA methodology. Experimental data confirmed the copresence of DOPA decarboxylase (DDC) and angiotensin converting enzyme 2 (ACE2) in human and rodent enterocytes. The intestinal barrier structure and integrity can be altered by angiotensin (1-7) and dopamine (DA). Both renin–angiotensin and dopaminergic systems influence intestinal Na+/K+-ATPase activity, thus maintaining electrolyte and nutritional homeostasis. The colocalization of B0AT1 and ACE2 indicates the direct role of the renin–angiotensin system in amino acid absorption. Yet, more studies are needed to thoroughly define the structural and functional interaction between TJ-associated proteins and GI renin–angiotensin and dopaminergic systems. Full article
(This article belongs to the Special Issue Role of Dopamine in Health and Disease: Biological Aspect 2.0)
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21 pages, 1794 KiB  
Review
Anti-Inflammatory Effects of Peripheral Dopamine
by Shaun C. Moore, Pedro A. S. Vaz de Castro, Daniel Yaqub, Pedro A. Jose and Ines Armando
Int. J. Mol. Sci. 2023, 24(18), 13816; https://doi.org/10.3390/ijms241813816 - 7 Sep 2023
Cited by 9 | Viewed by 2714
Abstract
Dopamine is synthesized in the nervous system where it acts as a neurotransmitter. Dopamine is also synthesized in a number of peripheral organs as well as in several types of cells and has organ-specific functions and, as demonstrated more recently, is involved in [...] Read more.
Dopamine is synthesized in the nervous system where it acts as a neurotransmitter. Dopamine is also synthesized in a number of peripheral organs as well as in several types of cells and has organ-specific functions and, as demonstrated more recently, is involved in the regulation of the immune response and inflammatory reaction. In particular, the renal dopaminergic system is very important in the regulation of sodium transport and blood pressure and is particularly sensitive to stimuli that cause oxidative stress and inflammation. This review is focused on how dopamine is synthesized in organs and tissues and the mechanisms by which dopamine and its receptors exert their effects on the inflammatory response. Full article
(This article belongs to the Special Issue Role of Dopamine in Health and Disease: Biological Aspect 2.0)
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