Dopamine Mechanisms Research Articles

Intelligent luminescent microneedle and hydrogel patches for visual monitoring of lactic acid and dopamine

Dopamine (DA) and lactic acid (LA) are vital biochemical indicators of neurotransmitters and tissue oxidation monitoring, which can comprehensively assess the neurological and physical conditions. The combination of fluorescent sensor and artificial intelligence shows great potentials in monitoring and quantizing of human biochemicals. Herein, a Tb3+ functionalized hydrogen-bonded organic framework material (Tb@ME-TPA) is synthesized based on coordination post-synthesis modification, and its sensing mechanism for DA and LA is investigated by experiments and theoretical calculations. For visual detection of DA and LA in actual environment, Tb@ME-TPA is fabricated into PVA films and microneedle patches, which hold the advantages of high efficiency, sensitivity and anti-interference. In addition, microneedles-based probe for minimally invasive sensing of DA in the dermal interstitial fluid along with a portable smartphone platform are designed to monitor with high accuracy. Furthermore, an intelligent back-propagation neural network model based on fluorescence image recognition is constructed, which can combine optical sensing of LA with deep learning by computer, greatly improving the efficiency and accuracy. This work not only presents a novel idea for the integration of fluorescent materials, smartphones and deep learning, but also provides an effective method for the prediction of diseases as well as the real-time monitoring of overall well-being.

Dopamine, an exogenous quorum sensing signaling molecule or a modulating factor in Pseudomonas aeruginosa?

Pseudomonas aeruginosa is recognized globally as an opportunistic pathogen of considerable concern due to its high virulence and pathogenicity, especially in immunocompromised individuals. While research has identified several endogenous quorum sensing (QS) signaling molecules that enhance the virulence and pathogenicity of P. aeruginosa, investigations on exogenous QS signaling molecules or modulating factors remain limited. This study found that dopamine serves as an exogenous QS signaling molecule or modulating factor of P. aeruginosa PAO1, enhancing the production of virulence factors and biofilms. Compared to the control group, treatment with 40 μM dopamine resulted in a 33.1 % increase in biofilm formation, 68.1 % increase in swimming mobility, 63.1 % increase in swarming mobility, 147.2 % increase in the signaling molecule 3-oxo-C12-HSL, and 50.5 %, 28.5 %, 27.0 %, and 33.2 % increases in the virulence factors alginate, rhamnolipids, protease, and pyocyanin, respectively. This study further explored the mechanism of dopamine regulating the biofilm formation and virulence of P. aeruginosa PAO1 through transcriptome and metabolome. Transcriptomic analysis showed that dopamine promoted the expression of virulence genes psl, alg, lasA, rhlABC, rml, and phz in P. aeruginosa PAO1. Metabolomic analysis revealed changes in the concentrations of tryptophan, pyruvate, ethanolamine, glycine, 3-hydroxybutyric acid, and alizarin. Furthermore, KEGG enrichment analysis of altered genes and metabolites indicated that dopamine enhanced phenylalanine, tyrosine, and tryptophan in P. aeruginosa PAO1. The results of this study will contribute to the development of novel exogenous QS signaling molecules or modulating factors and advance our understanding of the interactions between P. aeruginosa and the host environment.

MnO2 nanosheets based catechol oxidase mimics for robust electrochemical sensor: Synthesis, mechanism and its application for ultrasensitive and selective detection of dopamine

Nanozymes have favorable activity and good stability, which are potential alternatives to natural enzymes and widely applied in biosensing. However, nanozymes based electrochemical sensors are fewer, because many nanozymes are not easy to form efficient electrocatalytic interface and experience interference from the possible oxidizable species. Herein, ultrathin MnO2 nanosheets (MnO2 NSs) were synthesized by reduction of KMnO4 in acidic environment by chemical precipitation method. The MnO2 NSs show excellent catechol oxidase mimicking activity. The steady-state kinetics of MnO2 NSs shows a higher Vmax of 3.441 µM s−1. Additionally, the catalytic mechanism is that in the presence of oxygen, catechol or its analogues are oxidized to quinone or quinoids, while oxygen is reduced to H2O. Afterwards, the possible mechanism of dopamine (DA) at MnO2 NSs-modified electrode is investigated. DA is first catalytically oxidized to dopamine quinone (DQ) by MnO2 NSs based catechol oxidase, which further undergoes irreversible electrochemical reduction to DA involving two protons and two electrons transfer during the process. On the basis of this, a selective and ultrasensitive amperometric detection of DA at 0.0 V (vs. SCE) was explored, which have two linear parts, 0.01–20 μM and 20–100 μM DA with the LOD of 4.1 nM (S/N = 3). Most importantly, the presence of oxidizable species including ascorbic acid, uric acid and cysteine may coexist with DA in biological systems do not exhibit any appreciable interference. The as-proposed method was applicable to detect DA in human serum samples with good satisfactory accuracy and recovery. This research casts prospect to apply nanozymes for electrochemical sensor with excellent analytical performance.

Electrochemical and quantum chemical approaches to the study of dopamine sensing using bentonite and l-cysteine modified carbon paste electrode

This work presents a significant investigation involving both electrochemical experiment and quantum chemical simulation approaches. The objective was to characterize the electrochemical detection of dopamine (DA). The detection was carried out using a modified carbon paste electrode (CPE) incorporating bentonite (Bent) and l-cysteine (CySH) (named as CySH/Bent/CPE). To understand and explain the oxidation mechanism of DA on the CySH/Bent modified electrode surface, the coupling of the two approaches were exploited. The CySH/Bent/CPE showed excellent electroactivity toward DA such as good sensibility, selectivity, stability, and regenerative ability. The developed sensor shows a dynamic linear range from 0.8 to 80 μM with a limit of detection and quantification of 0.5 μM and 1.5 μM, respectively. During the quantitative analysis of DA in presence of ascorbic acid (AA) and uric acid (UA) the electrochemical oxidation signals of AA, DA, and UA distinctly appear as three separate peaks. The potential differences between the peaks are 190 mv, 150 mv, and 340 mV for the AA–DA, DA–UA, and AA–UA oxidation pairs, respectively. These observations stem from square wave voltammetry (SWV) studies, along with the corresponding redox peak potential separations. The developed sensor is simple and accurate to monitor DA in human serum samples. On the other hand, CySH acts as an electrocatalyst on the CySH/Bent/CPE surface by increasing its active electron transfer sites, as suggested by the quantum chemical modeling with analytical results of Fukui. Furthermore, the voltammetric results obtained agree well with the theoretical calculations.

A dopamine mechanism for reward maximization

Individual survival and evolutionary selection require biological organisms to maximize reward. Economic choice theories define the necessary and sufficient conditions, and neuronal signals of decision variables provide mechanistic explanations. Reinforcement learning (RL) formalisms use predictions, actions, and policies to maximize reward. Midbrain dopamine neurons code reward prediction errors (RPE) of subjective reward value suitable for RL. Electrical and optogenetic self-stimulation experiments demonstrate that monkeys and rodents repeat behaviors that result in dopamine excitation. Dopamine excitations reflect positive RPEs that increase reward predictions via RL; against increasing predictions, obtaining similar dopamine RPE signals again requires better rewards than before. The positive RPEs drive predictions higher again and thus advance a recursive reward-RPE-prediction iteration toward better and better rewards. Agents also avoid dopamine inhibitions that lower reward prediction via RL, which allows smaller rewards than before to elicit positive dopamine RPE signals and resume the iteration toward better rewards. In this way, dopamine RPE signals serve a causal mechanism that attracts agents via RL to the best rewards. The mechanism improves daily life and benefits evolutionary selection but may also induce restlessness and greed.

Protective effects of dopamine against non-alcoholic steatohepatitis via inhibiting p65 pathways in vivo and in vitro.

Currently, the role and mechanism of dopamine in non-alcoholic steatohepatitis (NASH) remains unclear. In vitro experiments utilized FFA and LPS to establish NASH cell models, while a fibrotic cell model was created using TGFβ1 to investigate the impact of dopamine on cellular lipid metabolism, inflammation, and fibrosis. In vivo experiments involved the use of MCD and HFD diets to induce NASH in mouse models for observing the effects of dopamine on NASH disease progression. Our study showed that dopamine significantly downregulated the expression levels of Caspase 1, IL-1β and IL18 in the HepG2 NASH cell model. In addition, dopamine could inhibit the TGF-β1-induced accumulation of collagen I and α-SMA in LX2 cells. In vivo experiments have shown that dopamine attenuation in mice is associated with MCD diet-induced and HFD-induced steatohepatitis. Mechanically, dopamine inhibits the p65 signaling pathway in NASH. In conclusion, the present study demonstrates the role of dopamine in ameliorating the symptoms of NASH and provides a direction for future research on the application of the dopaminergic system to liver disease.

Insight into polydopamine coating on microfiltration membrane with controlled surface pore size for enhanced membrane rejection

Membrane modification with polydopamine (PDA) is a common practice to enhance membrane selectivity and improve membrane compatibility with nanoparticles or thin films. Depending on the membrane surface properties, dopamine can deposit or penetrate into microporous membranes, leading to alteration in the membrane's physicochemical properties and consequently its performance. In this study, microfiltration (MF) polyethersulfone membranes with varying surface pore sizes were fabricated by manipulating the precasting time (solvent evaporation time of 3s, 15s, 30s and 60s) prior to non-solvent induced phase separation (NIPS) process. Notably, the coating of PDA slightly reduced the membrane's surface pore size and membrane's porosity. M60 membrane which possessed the smallest mean surface pores (∼300 nm), exhibited PDA clusters predominantly formed on top of the membrane surface. With an increase in surface pore size, dopamine can penetrate the porous structure of the MF membrane, leading to the polymerization of dopamine into PDA aggregates on both the membrane surface and inner pores. The M30 membrane had the largest surface pore size (∼500 nm), showing the formation of large PDA globules in the finger-like pores. The membrane (M30P) experienced significant narrowing of the inner pores, resulting in reduced water permeability. Overall, all PDA-coated membranes exhibited improved sucrose rejection (85–95%) compared to the uncoated ones (64–83%). These finding provides insight into the polymerization mechanism of dopamine on porous membranes prior to the incorporation of nanomaterials or thin film coating.

A role for dopamine in control of the hypoxic ventilatory response via D2 receptors in the zebrafish gill.

Dopamine is a neurotransmitter involved in oxygen sensing and control of reflex hyperventilation. In aquatic vertebrates, oxygen sensing occurs in the gills via chemoreceptive neuroepithelial cells (NECs), but a mechanism for dopamine in autonomic control of ventilation has not been defined. We used immunohistochemistry and confocal microscopy to map the distribution of tyrosine hydroxylase (TH), an enzyme necessary for dopamine synthesis, in the gills of zebrafish. TH was found in nerve fibers of the gill filaments and respiratory lamellae. We further identified dopamine active transporter (dat) and vesicular monoamine transporter (vmat2) expression in neurons of the gill filaments using transgenic lines. Moreover, TH- and dat-positive nerve fibers innervated NECs. In chemical screening assays, domperidone, a D2 receptor antagonist, increased ventilation frequency in zebrafish larvae in a dose-dependent manner. When larvae were confronted with acute hypoxia, the D2 agonist, quinpirole, abolished the hyperventilatory response. Quantitative polymerase chain reaction confirmed expression of drd2a and drd2b (genes encoding D2 receptors) in the gills, and their relative abundance decreased following acclimation to hypoxia for 48h. We localized D2 receptor immunoreactivity to NECs in the efferent gill filament epithelium, and a novel cell type in the afferent filament epithelium. We provide evidence for the synthesis and storage of dopamine by sensory nerve terminals that innervate NECs. We further suggest that D2 receptors on presynaptic NECs provide a feedback mechanism that attenuates the chemoreceptor response to hypoxia. Our studies suggest that a fundamental, modulatory role for dopamine in oxygen sensing arose early in vertebrate evolution.

A novel dopamine electrochemical sensor based on multiwall carbon nanotubes-cetyltrimethylammonium bromide/nitrogen doped ultra-thin carbon nanosheets composites modified glassy carbon electrode

Dopamine (DA), as an important neurotransmitter, plays pivotal roles in addiction and some diseases. Fast and sensitive detection is of great value. Herein, a novel DA sensor based on multiwall carbon nanotubes-cetyltrimethylammonium bromide/zinc/cobalt @ nitrogen doped ultra-thin carbon nanosheets (MWCNTs-CTAB/Zn/Co@N-CNSs) was constructed. The 2D Zn/Co@N-CNSs was derived from the Zn/Co-ZIF precursor which was obtained by the simple salt stencil method. For the detection of DA, the MWCNTs-CTAB/Zn/Co@N-CNSs/GCE presented wide linear range (0.10 μM–12.0 μM) and low detection limit (LOD, 0.037 μM, (S/N = 3)).With the help of density function theory calculation results, the redox mechanism and electrochemical reaction sites of DA were further revealed. Besides, MWCNTs-CTAB/Zn/Co@N-CNSs/GCE achieved good recovery and accuracy in detecting DA in actual samples (bovine serum protein and human serum).

An electrochemical reductive approach for selective determination of dopamine based on its reverse voltammetric preoxidation and intramolecular cyclization

In this paper, the cyclic voltammetric behavior of dopamine (DA) was investigated systematically at different potential windows on electrochemical reduce graphene oxide modified glassy carbon electrode, and we found that the electrochemical redox mechanism of DA is a multi-step ECE process and the redox peak appearing at low potentials (∼–0.30 V) was dependent on the oxidation of DA at high potentials (∼0.20 V). The electrolyte enriched with the DA preoxidation product was then analyzed by LC-MS/MS and its structure was identified as dopaminochrome (DC). So, we proposed a new insight for the non-oxidative electrochemical analysis of DA by reverse voltammetry preoxidation and intramolecular cyclization. Compared with the traditional forward scaning mode, the approach could minimize the interference of ascorbic acid (AA) and enable the dual quantitative analysis of DA in the presence of high concentration of AA with the linear range of 2.0 to 80 μM and 60 to 200 μM, respectively, and a detection limit of 1.0 μM. Furthermore, the voltammetric properties of norepinephrine (NE), epinephrine (EP), 3,4-dihydroxy-l-phenylalanine (l-DOPA), 4-O-methyldopamine (HMP) were also investigated. The similar voltammetric properties to DA of NE, EP, l-DOPA and HMP suggested that the proposed reverse voltammetric preoxidation method is generalizable and equally applicable to monoamine neurotransmitters with a catechol structure.

A re-consideration of neural/receptor mechanisms in chemotherapy-induced nausea and vomiting: current scenario and future perspective.

The neural mechanisms and the receptors behind the course of chemotherapy-induced nausea and vomiting (CINV) are well described and considered mechanistically multifactorial, whereas the neurobiology of nausea is not completely understood yet. Some of the anti-neoplastic medications like cisplatin result in biphasic vomiting response. The acute phase of vomiting is triggered mainly via the release of serotonin from the enterochromaffin (EC) cells in the gastrointestinal tract (GIT) and results in stimulation of dorsal vagal complex (DVC) of the vomiting center and the vomiting is initiated by downward communication to the gut via vagal efferents. Agonism of 5HT3 receptors is majorly involved in the mediation of the acute phase. Therefore, antagonists at 5HT3 receptors are effective in the management of acute-phase vomiting episodes. Likewise, Dopamine type 2 (D2) receptors, dopamine neurotransmitter, Muscarinic receptors (M3), GLP1 receptors, and histaminergic receptors (H1) are also implicated in the vomiting act as well. In continuation, Cannabinoid type 1 (CB1) receptors are also recommended and included in the guidelines as agonism of presynaptically located CB1 receptors inhibits the release of excitatory neurotransmitters responsible for vomiting initiation. The delayed phase involves the release of "Substance P" in the gut and results in the stimulation of neurokinin-1 (NK1) receptors centrally in the area postrema (AP) and nucleus tractus solitarius (NTS), subsequently the vomiting response. The current understanding is the existence of overlapping mechanisms of neurotransmitters, serotonin, dopamine, and substance P throughout the time course of CINV. Furthermore, the emetic neurotransmitters are released via calcium ion (Ca++)-dependent mechanisms, implicating the molecular targets of intracellular Ca++ signaling in emetic circuitry. The current review entails the neurobiology of nausea and vomiting induced by cancer chemotherapeutic agents and the recent approaches in the management.

Recent Advances in Polydopamine for Surface Modification and Enhancement of Energetic Materials: A Mini-Review

Polydopamine (PDA), inspired by the adhesive mussel foot proteins, is widely applied in chemical, biological, medical, and material science due to its unique surface coating capability and abundant active sites. Energetic materials (EMs) play an essential role in both military and civilian fields as a chemical energy source. Recently, PDA was introduced into EMs for the modification of crystal phase stability and the interfacial bonding effect, and, as a result, to enhance the mechanical, thermal, and safety performances. This mini-review summarizes the representative works in PDA modified EMs from three perspectives. Before that, the self-polymerization mechanisms of dopamine and the methods accelerating this process are briefly presented for consideration of researchers in this field. The future directions and remaining issues of PDA in this field are also discussed at last in this mini-review.

Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis.

Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.

Dual electrochemical quantitative analysis of dopamine based on flow injection amperometry with double glassy carbon electrodes

A simple, rapid and stable electrochemical flow injection amperometry (FI-Amp) system based on a flow cell with two glassy carbon electrodes arranged in series was constructed and the redox mechanism of dopamine (DA) was investigated as a research model. Electrochemical oxidation of DA occurs at the surface of the first working electrode (WE1, +0.24 V working potential), and then its oxidation product undergoes electrochemical reduction when it flows through the second working electrode (WE2, +0.05 V working potential). The source of the reduction currents on the WE2 was discussed and finally identified as dopaquinone (DAQ). In addition, dual quantitative analysis of DA was achieved by the oxidation current of DA on WE1 and the reduction current of DAQ on WE2. Under optimized conditions, the dual linear response ranges for DA were from 0.5 µM to 250 µM and 2 µM to 250 µM, and the dual limits of detection were found to be 0.20 µM and 0.68 µM (S/N = 3), respectively. Moreover, the RSDs of the amperometric responses for 5 µM, 50 µM and 200 µM DA were all less than 10% over 50 repeated injections, showing that the FI-Amp system has excellent repeatability and stability. The approach is universal and superior to the traditional three-electrode system. It can be used to study the mechanisms of molecular redox reactions and has great potential for application in the electrochemical identification of other electroactive molecules.

Dopamine alleviates cadmium stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed by high-throughput sequencing and soil metabolomics.

Dopamine has demonstrated promise as a stress-relief substance. However, the function of dopamine in Cd tolerance and its mechanism remains largely unknown. The current study was performed to investigate the mechanism of dopamine on alleviating apple Cd stress through regular application of CdCl2 and dopamine solution to potting soil. The results indicated that dopamine significantly reduced reactive oxygen species (ROS) and Cd accumulation and alleviated the inhibitory effect of Cd stress on the growth of apple plants through activation of the antioxidant system, enhancement of photosynthetic capacity, and regulation of gene expression related to Cd absorption and detoxification. The richness of the rhizosphere microbial community increased, and community composition and assembly were affected by dopamine treatment. Network analysis of microbial communities showed that the numbers of nodes and total links increased significantly after dopamine treatment, while the keystone species shifted. Linear discriminant analysis effect size indicated that some biomarkers were significantly enriched after dopamine treatment, suggesting that dopamine induced plants to recruit potentially beneficial microorganisms (Pseudoxanthomonas, Aeromicrobium, Bradyrhizobium, Frankia, Saccharimonadales, Novosphingobium, and Streptomyces) to resist Cd stress. The co-occurrence network showed several metabolites that were positively correlated with relative growth rate and negatively correlated with Cd accumulation, suggesting that potentially beneficial microorganisms may be attracted by several metabolites (L-threonic acid, profenamine, juniperic acid and (3β,5ξ,9ξ)-3,6,19-trihydroxyurs-12-en-28-oic acid). Our results demonstrate that dopamine alleviates Cd stress in apple trees by recruiting beneficial microorganisms to enhance the physiological resilience revealed. This study provides an effective means to reduce the harm to agricultural production caused by heavy metals.

Mussel-inspired quaternary composite hydrogels with high strength and high tissue adhesion for transdermal drug delivery: Synergistic hydrogen bonding and drug release mechanism

Low adhesion to skin remains a significant challenge for most hydrogel based transdermal drug delivery systems. Meanwhile, most of the methods to improve bio-adhesion often ignore the effect of the cohesion. Inspired by the adhesion mechanism of natural mussels and the synergistic balance theory based on cohesion and adhesion, we designed a poly (acrylamide-co-hydroxyethyl acrylate)-polydopamine-polyvinylpyrrolidone (PAHDP) quaternary composite hydrogel to enhance the cohesion and adhesion through the synergistic effect of multiple hydrogen bonds to achieve strong bio-adhesion to skin. The structure of PAHDP was characterized by FTIR, 1H NMR, SEM and TGA. The peeling adhesion force of PAHDP on porcine skin was improved by 9-fold compared with PAH hydrogel. At the same time, the adhesion force of drug-loaded PAHDP was 1.3 times that of Voltaren®EX. The rheological test further demonstrated that the synergistic hydrogen bonding can significantly improve the PAHDP cohesion. In addition, in vitro release, skin permeation and pharmacokinetics test of PAHDP hydrogel containing diclofenac sodium (DIC) showed that monomer dopamine (DA) could promote drug release. FTIR and molecular modeling were utilized to further demonstrate the enhanced drug release mechanism of DA. MTT assay, H&E staining and skin erythema analysis demonstrated that PAHDP was non-irritant to the skin. In conclusion, the innovatively prepared PAHDP hydrogel exhibits high skin adhesion, excellent mechanical properties, non-irritation and high drug release ability. This study also provides a simple and efficient strategy and theoretical basis for the preparation of high adhesion and high drug release hydrogels for transdermal drug delivery system.

A novel dopamine electrochemical sensor based on 3D flake nickel oxide/ cobalt oxide @ porous carbon nanosheets/carbon nanotubes/electrochemical reduced of graphene oxide composites modified glassy carbon electrode

Dopamine (DA), as an typical neurotransmitter, was believed to play important roles in addiction and some neurodegenerative diseases. Accurately and rapidly detection of DA is very valuable. In this study, a sensor based on 3D flake nickel oxide/ cobalt oxide@porous carbon nanosheets/carbon nanotubes/ electrochemical reduced of graphene oxide composites modified glassy carbon electrode (NiO/CoO@PCNs/CNTs/erGO/GCE) was constructed. The flake NiO/CoO@PCNs/CNTs were obtained by directly pyrolysis Ni/Co-MOF under nitrogen protection, which presented excellent electrochemical properties due to the synergistic catalytic effect and porous sheet structure. For the detection of DA, the NiO/CoO@PCNs/CNTs/erGO/GCE showed wider linear range (0.10 μM – 22.0 μM) and the detection limit (LOD) of DA was 0.045 μM, (S/N = 3). Additionally, the reaction sites and mechanism of DA were revealed by analyzing the electrochemical behavior with the help of density functional calculation. Moreover, the sensor showed satisfactory results in the determination of DA in real biological sample.

Ultrasensitive and Simple Dopamine Electrochemical Sensor Based on the Synergistic Effect of Cu-TCPP Frameworks and Graphene Nanosheets

Dopamine (DA) is an important neurotransmitter. Abnormal concentration of DA can result in many neurological diseases. Developing reliable determination methods for DA is of great significance for the diagnosis and monitoring of neurological diseases. Here, a novel and simple electrochemical sensing platform for quantitative analysis of DA was constructed based on the Cu-TCPP/graphene composite (TCPP: Tetrakis(4-carboxyphenyl)porphyrin). Cu-TCPP frameworks were selected in consideration of their good electrochemical sensing potential. The graphene nanosheets with excellent conductivity were then added to further improve the sensing efficiency and stability of Cu-TCPP frameworks. The electrochemical properties of the Cu-TCPP/graphene composite were characterized, showing its large electrode active area, fast electron transfer, and good sensing performance toward DA. The signal enhancement mechanism of DA was explored. Strong accumulation ability and high electrocatalytic rate were observed on the surface of Cu-TCPP/graphene-modified glassy carbon electrode (Cu-TCPP/graphene/GCE). Based on the synergistic sensitization effect, an ultrasensitive and simple DA electrochemical sensor was developed. The linear range is 0.02-100 and 100-1000 µM, and the detection limit is 3.6 nM for the first linear range. It was also successfully used in detecting DA in serum samples, and a satisfactory recovery was obtained.

Dopamine Dynamics and Neurobiology of Non-Response to Antipsychotics, Relevance for Treatment Resistant Schizophrenia: A Systematic Review and Critical Appraisal

Treatment resistant schizophrenia (TRS) is characterized by a lack of, or suboptimal response to, antipsychotic agents. The biological underpinnings of this clinical condition are still scarcely understood. Since all antipsychotics block dopamine D2 receptors (D2R), dopamine-related mechanisms should be considered the main candidates in the neurobiology of antipsychotic non-response, although other neurotransmitter systems play a role. The aims of this review are: (i) to recapitulate and critically appraise the relevant literature on dopamine-related mechanisms of TRS; (ii) to discuss the methodological limitations of the studies so far conducted and delineate a theoretical framework on dopamine mechanisms of TRS; and (iii) to highlight future perspectives of research and unmet needs. Dopamine-related neurobiological mechanisms of TRS may be multiple and putatively subdivided into three biological points: (1) D2R-related, including increased D2R levels; increased density of D2Rs in the high-affinity state; aberrant D2R dimer or heteromer formation; imbalance between D2R short and long variants; extrastriatal D2Rs; (2) presynaptic dopamine, including low or normal dopamine synthesis and/or release compared to responder patients; and (3) exaggerated postsynaptic D2R-mediated neurotransmission. Future points to be addressed are: (i) a more neurobiologically-oriented phenotypic categorization of TRS; (ii) implementation of neurobiological studies by directly comparing treatment resistant vs. treatment responder patients; (iii) development of a reliable animal model of non-response to antipsychotics.

Adsorption characteristics of dopamine by activated carbon: Experimental and theoretical approach

In this work, we investigate the adsorption mechanism of dopamine (DP) drug using an activated carbon (AC) type through experimental and theoretical data. Experiment series were carried out at different initial values of solution pH, temperature, reaction time and initial drug concentration. The effect of protonation and deprotonation of DP molecule was also investigated. The equilibrium isotherm data were evaluated using the Dubinin-Radushkevich, Langmuir, Temkin and Freundlich models. Elovich, pseudo-first and pseudo-second order kinetic models were used to analyze kinetic data. Here we also used molecular dynamic (MD) simulation and DFT-based computational methods to reach information about the electronic properties of DP drug and its adsorption mechanism that have not been experimentally observed. Experimental results show that the Elovich kinetic model and Langmuir model best describe the adsorption phenomenon. In parallel, the experimental analysis revealed that the adsorption process is spontaneous and endothermic. Dopamine adsorption on AC occurs quickly and is pH and temperature-dependent. Frontier molecular orbital (FMO) energies for neutral, deprotonated and protonated forms of DP were determined and thoroughly explained. The basic medium significantly impacts DP drug adsorption behavior, which has the greatest adsorption energy when the pH is less than 12. It was found that DP adsorption occurs in a bidentate geometry by forming strong bonds between molecular oxygens and carbon atoms on the AC surface. Based on theoretical calculations interaction mechanisms of DP on the AC (001) surface were proposed.