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The Physiology and Pharmacology of Dopamine Receptors: From Normal Signaling...
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The Physiology and Pharmacology of Dopamine Receptors: From Normal Signaling to Pathology

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (28 October 2022) | Viewed by 11636

Special Issue Editor

Prof. Dr. Jaromír Mysliveček

E-Mail Website
Guest Editor
Institute of Physiology, 1st Faculty of Medicine, Charles University, Albertov 5, 128 00 Prague, Czech Republic
Interests: muscarinic receptors; biological rhythm; behavior; locomotor activity; dopamine receptors; adrenoceptors; stress

Special Issue Information

Dear Colleagues,

The neurotransmitter dopamine, belonging to catecholamines, is an important molecule that activates two classes of receptors: D1-like and D2-like. Both these groups comprise more receptor subtypes: D1-like includes D1 and D5 dopamine receptors, and D2-like includes D2, D3 and D4 dopamine receptors. These groups also differ in signaling—while D1-like mostly activates adenylyl cyclase, D2-like receptors inhibit this enzyme. Dopamine receptors are expressed in many tissues in the organisms. In the central nervous system, they affect locomotion, they play a role in reward behavior, in neuroendocrine control, and in emotion. However, they also play an important role in the periphery: they have immunomodulatory effects in inflammatory diseases, they affect important functions of the cardio-pulmonary system, as well as renal functions. Pathologies in dopamine receptor, thus, have led to many diseases such as schizophrenia, addiction, Parkinson's disease, genetic hypertension and others. This Special Issue on “The Physiology and Pharmacology of Dopamine Receptors: From Normal Signaling to Pathology” will present a selection of original research papers or reviews that address these topics.

Prof. Dr. Jaromír Mysliveček
Guest Editor

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Keywords

  • dopamine receptor
  • signaling
  • Parkinson’s disease
  • addiction
  • inflammation
  • central nervous system
  • peripheral dopamine

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Published Papers (4 papers)

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Research

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21 pages, 2563 KiB  
Article
Hypothalamic A11 Nuclei Regulate the Circadian Rhythm of Spinal Mechanonociception through Dopamine Receptors and Clock Gene Expression
by Celia Piña-Leyva, Manuel Lara-Lozano, Marina Rodríguez-Sánchez, Guadalupe C. Vidal-Cantú, Ericka Barrientos Zavalza, Ismael Jiménez-Estrada, Rodolfo Delgado-Lezama, Leonardo Rodríguez-Sosa, Vinicio Granados-Soto, Juan Antonio González-Barrios and Benjamín Florán-Garduño
Life 2022, 12(9), 1411; https://doi.org/10.3390/life12091411 - 10 Sep 2022
Cited by 2 | Viewed by 2823
Abstract
Several types of sensory perception have circadian rhythms. The spinal cord can be considered a center for controlling circadian rhythms by changing clock gene expression. However, to date, it is not known if mechanonociception itself has a circadian rhythm. The hypothalamic A11 area [...] Read more.
Several types of sensory perception have circadian rhythms. The spinal cord can be considered a center for controlling circadian rhythms by changing clock gene expression. However, to date, it is not known if mechanonociception itself has a circadian rhythm. The hypothalamic A11 area represents the primary source of dopamine (DA) in the spinal cord and has been found to be involved in clock gene expression and circadian rhythmicity. Here, we investigate if the paw withdrawal threshold (PWT) has a circadian rhythm, as well as the role of the dopaminergic A11 nucleus, DA, and DA receptors (DR) in the PWT circadian rhythm and if they modify clock gene expression in the lumbar spinal cord. Naïve rats showed a circadian rhythm of the PWT of almost 24 h, beginning during the night–day interphase and peaking at 14.63 h. Similarly, DA and DOPAC’s spinal contents increased at dusk and reached their maximum contents at noon. The injection of 6-hydroxydopamine (6-OHDA) into the A11 nucleus completely abolished the circadian rhythm of the PWT, reduced DA tissue content in the lumbar spinal cord, and induced tactile allodynia. Likewise, the repeated intrathecal administration of D1-like and D2-like DA receptor antagonists blunted the circadian rhythm of PWT. 6-OHDA reduced the expression of Clock and Per1 and increased Per2 gene expression during the day. In contrast, 6-OHDA diminished Clock, Bmal, Per1, Per2, Per3, Cry1, and Cry2 at night. The repeated intrathecal administration of the D1-like antagonist (SCH-23390) reduced clock genes throughout the day (Clock and Per2) and throughout the night (Clock, Per2 and Cry1), whereas it increased Bmal and Per1 throughout the day. In contrast, the intrathecal injection of the D2 receptor antagonists (L-741,626) increased the clock genes Bmal, Per2, and Per3 and decreased Per1 throughout the day. This study provides evidence that the circadian rhythm of the PWT results from the descending dopaminergic modulation of spinal clock genes induced by the differential activation of spinal DR. Full article
(This article belongs to the Special Issue The Physiology and Pharmacology of Dopamine Receptors: From Normal Signaling to Pathology)
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16 pages, 5967 KiB  
Article
Alterations of Dopamine Receptors and the Adaptive Changes of L-Type Calcium Channel Subtypes Regulate Cocaine-Seeking Habit in Tree Shrew
by Ying Duan, Lingtong Jin, Wenjie Du, Shubo Jin, Yiming Meng, Yonghui Li, Jianjun Zhang, Jing Liang, Nan Sui and Fang Shen
Life 2022, 12(7), 984; https://doi.org/10.3390/life12070984 - 30 Jun 2022
Cited by 1 | Viewed by 1932
Abstract
The putamen (Put) is necessary for habitual actions, while the nucleus caudate (Cd) is critical for goal-directed actions. However, compared with the natural reward (such as sucrose)-seeking habit, how drug-related dysfunction or imbalance between the Put and Cd is involved in cocaine-seeking habit, [...] Read more.
The putamen (Put) is necessary for habitual actions, while the nucleus caudate (Cd) is critical for goal-directed actions. However, compared with the natural reward (such as sucrose)-seeking habit, how drug-related dysfunction or imbalance between the Put and Cd is involved in cocaine-seeking habit, which is not easy to bias behavior to goal-directed actions, is absent. Therefore, in our present study, in comparison with sucrose-habitual behavior, we evaluated the distinctive changes of the two subtypes of dopamine (DA) receptors (D1R and D2R) in cocaine-seeking habitual behavior animals. Moreover, the adaptive changes of Cav1.2 and Cav1.3, as prime downstream targets of D1R and D2R respectively, were also assessed. Our results showed that a similar percentage of the animals exhibited habitual seeking behavior after cocaine or sucrose variable-interval self-administration (SA) training in tree shrews. In addition, compared with animals with non-habitual behavior, animals with cocaine habitual behavior showed higher D1Rs and Cav1.2 expression in the Put accompanied with lower D2Rs and Cav1.3 expression in the Cd. However, after sucrose SA training, animals with habitual behavior only showed lower membrane expression of D2R in the Put than animals with non-habitual behavior. These results suggested that the upregulation of D1Rs-Cav1.2 signaling may lead to hyper-excitability of the Put, and the inactivation of D2Rs-Cav1.3 signaling may result in depressed activity in the Cd. This imbalance function between the Put and Cd, which causes an inability to shift between habits and goal-directed actions, may underlie the compulsive addiction habit. Full article
(This article belongs to the Special Issue The Physiology and Pharmacology of Dopamine Receptors: From Normal Signaling to Pathology)
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20 pages, 3821 KiB  
Article
Modulation by Estradiol of L-Dopa-Induced Dyskinesia in a Rat Model of Post-Menopausal Hemiparkinsonism
by Kaja Kolmančič, Marko Živin and Maja Zorović
Life 2022, 12(5), 640; https://doi.org/10.3390/life12050640 - 26 Apr 2022
Cited by 1 | Viewed by 2313
Abstract
Treatment with levodopa (L-dopa) in Parkinson’s disease (PD) leads to involuntary movements termed L-dopa-induced dyskinesia (LID). There are contradictory data about the influence of hormone therapy in female PD patients with LID and of 17-β-estradiol (E2) on animal correlates of LID-abnormal involuntary movements [...] Read more.
Treatment with levodopa (L-dopa) in Parkinson’s disease (PD) leads to involuntary movements termed L-dopa-induced dyskinesia (LID). There are contradictory data about the influence of hormone therapy in female PD patients with LID and of 17-β-estradiol (E2) on animal correlates of LID-abnormal involuntary movements (AIMs). Our aim was to characterize the influence of E2 on motor impairment and AIMs in ovariectomized 6-hydroxydopamine (6-OHDA) rat model of PD. Half of the rats received empty and the other half implants filled with E2. Following the 6-OHDA surgery, the rats received daily treatment with either L-dopa or saline for 16 days. They were assessed for AIMs, contralateral rotations, and FAS. In the L-dopa-treated rats, E2 intensified and prolonged AIMs and contralateral rotations. On the other hand, it had no effect on motor impairment. Postmortem tyrosine hydroxylase immunostaining revealed an almost complete unilateral lesion of nigrostriatal dopaminergic neurons. E2 partially prevented the upregulation of striatal ΔFosB caused by dopamine depletion. L-dopa potentiated the upregulation of ΔFosB within the dopamine-depleted striatum and this effect was further enhanced by E2. We speculate that the potentiating effects of E2 on AIMs and on contralateral rotations could be explained by the molecular adaptations within the striatal medium spiny neurons of the direct and indirect striatofugal pathways. Full article
(This article belongs to the Special Issue The Physiology and Pharmacology of Dopamine Receptors: From Normal Signaling to Pathology)
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Review

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19 pages, 598 KiB  
Review
Dopamine and Dopamine-Related Ligands Can Bind Not Only to Dopamine Receptors
by Jaromir Myslivecek
Life 2022, 12(5), 606; https://doi.org/10.3390/life12050606 - 19 Apr 2022
Cited by 8 | Viewed by 3566
Abstract
The dopaminergic system is one of the most important neurotransmitter systems in the central nervous system (CNS). It acts mainly by activation of the D1-like receptor family at the target cell. Additionally, fine-tuning of the signal is achieved via pre-synaptic modulation [...] Read more.
The dopaminergic system is one of the most important neurotransmitter systems in the central nervous system (CNS). It acts mainly by activation of the D1-like receptor family at the target cell. Additionally, fine-tuning of the signal is achieved via pre-synaptic modulation by the D2-like receptor family. Some dopamine drugs (both agonists and antagonists) bind in addition to DRs also to α2-ARs and 5-HT receptors. Unfortunately, these compounds are often considered subtype(s) specific. Thus, it is important to consider the presence of these receptor subtypes in specific CNS areas as the function virtually elicited by one receptor type could be an effect of other—or the co-effect of multiple receptors. However, there are enough molecules with adequate specificity. In this review, we want to give an overview of the most common off-targets for established dopamine receptor ligands. To give an overall picture, we included a discussion on subtype selectivity. Molecules used as antipsychotic drugs are reviewed too. Therefore, we will summarize reported affinities and give an outline of molecules sufficiently specific for one or more subtypes (i.e., for subfamily), the presence of DR, α2-ARs, and 5-HT receptors in CNS areas, which could help avoid ambiguous results. Full article
(This article belongs to the Special Issue The Physiology and Pharmacology of Dopamine Receptors: From Normal Signaling to Pathology)
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