Selective Dopamine Research Articles

Self-assembly of simple Schiff base ligand into unique saddle-type [4x4] tetranuclear architecture and its application as selective voltammetric dopamine sensor in aqueous conditions

Dopamine, a crucial catecholamine neurotransmitter, plays essential roles in the operation of the central nervous system in humans. Disrupted dopamine release is associated with neurological disorders and depression, therefore monitoring of dopamine levels is imperative for preliminary disease detection. Development of sensitive and selective sensors for neurotransmitters that function under aqueous conditions is however still challenging, mostly due to the complexity of hybrid nanomaterials that are interacting with the electrode. Here we provide a coordination compound constructed from simple substrates, where subcomponent self-assembly leads to a unique, discrete [4 × 4] saddle-type complex [Cu4(L-H)4(BF4)2(MeOH)2](BF4)2, which was characterized by ESI-MS and FT-IR techniques, including single crystal X-ray diffraction. The Cu4L4 complex was subsequently used for modification of the bare Au electrode based on its accumulation on the electrode surface. The new voltammetric sensor (Au/complex) was applied for dopamine detection alone and in the presence of interfering ascorbic acid by using the Differential Pulse Voltammetry (DPV) techniques under aqueous conditions. In the linear dynamic range (LDR) range from 0.0001 mM to 0.75 mM the dependence of the peak current on dopamine concentration satisfied the following linear regression equation: ip [mA] = 17∙10−2cDA [mM] + 8∙10−2 (R2 = 0.998). Moreover, the excellent limit of dopamine detection (LOD) and the limit of its quantification (LOQ) were established at the level of 5.4 nM and 18.0 nM with accomplished high sensitivity 0.17 A M−1, repeatability as well as reproducibility. Clear separation of the voltammetric signal of dopamine from this one of ascorbic acid, even in the presence of a 100-fold excess of interfering ions found in water, consequently proves that the new prepared sensor can be used as an excellent analytical tool for selective detection of dopamine and ascorbic acid coexisting in the tested samples.

6-Nitrodopamine is an endogenous mediator of the rabbit corpus cavernosum relaxation.

6-Nitrodopamine (6-ND) is a novel endogenous catecholamine that has a potent relaxant action on vascular smooth muscle in vitro. To evaluate the basal release of 6-ND and noradrenaline from rabbit-isolated corpus cavernosum (RbCC) and its relaxing action on this tissue. Rabbit corpus cavernosa were dissected and suspended in a 5-mL organ bath containing oxygenated Krebs-Henseleit's solution. 6-ND and noradrenaline release was quantified by liquid chromatography coupled to tandem mass spectrometry. The relaxant activity of 6-ND was assessed in RbCC strips pre-contracted with endothelin-1 (10nM). Rabbit corpus cavernosum presented basal release of both 6-ND (2.9±0.8ng/mL, n=12) and noradrenaline (1.7±1.3ng/mL, n=12). The 6-ND release was reduced by pre-treatment with Nω-nitro-l-arginine methyl ester (l-NAME) (100 µM), whereas that of noradrenaline was unaffected. Tetrodotoxin (TTX, 1 µM) abolished the noradrenaline release but had no effect on 6-ND release, indicating a non-neurogenic origin for 6-ND. 6-ND and the selective dopamine D2-agonist L-741,626 caused concentration-dependent RbCC relaxations (pEC50 of 11±0.15 and 11.15±0.28, respectively). Pre-treatment with either l-NAME or the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-on (ODQ) (100 µM) caused a rightward shift of the concentration-response curve to 6-ND, without affecting the L-741,626 responses. In TTX (100nM)-pre-treated preparations, neither l-NAME nor ODQ shifted the 6-ND concentration-response curve. Dopamine, noradrenaline, and adrenaline caused concentration-dependent RbCC contractions. Pre-incubation with 6-ND concentration-dependently inhibited the dopamine-induced contractions, without affecting those induced by either noradrenaline or adrenaline. 6-Nitrodopamine is the most potent endogenous relaxant agent in RbCC ever described and represents a novel mechanism by which NO causes corpus cavernosum smooth muscle relaxation. The finding that 6-ND acts as a truly selective dopamine D2-receptor antagonist indicates that the balance of dopamine and 6-ND release/synthesis may be the main mechanism that modulates corpus cavernosum smooth muscle tonus in vivo.

Highly sensitive and selective dopamine determination using a photoelectrochemical sensor based on the BiVO4 and surface molecularly imprinted poly(acrylic acid-co-TRIM) on vinyl functionalized carbon nanotubes

This paper describes the development of a new photoelectrochemical (PEC) sensor for dopamine (DA) determination based on the nanocomposite constituted of a molecularly imprinted poly(acrylic acid-co-TRIM) functionalized onto MWCNT with vinyl groups (MWCNT-MIP) physically mixed with monoclinic bismuth vanadate. Synthesized polymeric materials were characterized by FT-IR, TGA, SEM and TEM. The sensor based on glassy carbon electrode modified with BiVO4/MWCNT-MIP provided a limit of detection (LOD) of 31.1 nmol/L and a linear range from 103.6 to 2500 nmol/L. The proposed sensor exhibited selectivity to DA in competitive analysis with epinephrine, norepinephrine, ascorbic acid, citric acid, uric acid, creatine and urea, and it was applied for analysis of DA in simulated urine samples using external calibration curve with accuracy attested by recovery values between 91 and 106 %.

NCOG-33. GLIOBLASTOMA AND PARKINSONISM, IS DEPLETED DOPAMINE A PROTECTIVE SURVIVAL FACTOR? A CASE SERIES OF 3 GBM PATIENTS

Abstract Glioblastoma multiforme (GBM) is the most common malignant brain tumor, and carries a grave prognosis with a median survival of 15 months. The pathophysiologic hallmark of Parkinson’s disease is neuronal loss of dopamine producing cells in the substantia nigra. Dopamine has been shown to modify cell-cycle status in neural progenitor cells. Dopamine agonism is adequate to increase progenitor proliferation in the subventricular zone (SVZ). Dopamine receptor antagonists have antiproliferative effects. A few clinical trials use selective dopamine receptor D2 (DRD2) inhibitors. Parkinsonism can have organic etiologies like stroke or neoplasm, while idiopathic Parkinsonism is known as Parkinson’s disease. While uncommon to have dual diagnoses, we identified three patients with both GBM and Parkinsonism, all were IDH wildtype, 2 patients were MGMT methylated, mean age was 67 years. Our 3 patients have a combined median PFS of 23.4 months, mean PFS of 25.4 months, which compares favorably to historical control median PFS of 6.9 months. Our 3 patients with dual diagnosis have a median OS of 47.3 months, and mean OS of 43.7 months, which compares favorably to historical median OS of 14.6 months. One might expect a patient with a neurodegenerative disease like Parkinson’s disease and a highly malignant tumor like GBM to have an extremely poor prognosis, yet our patient cohort reveals the opposite. The improved overall survival in GBM patients with Parkinsonism supports further clinical research into selective dopamine receptor inhibitors.

Selective dopamine D2 receptor deletion from Nkx6.2 expressing cells causes impaired cognitive, motivation and anxiety phenotypes in mice

Abnormal dopamine neurotransmission is a common trait of some psychiatric diseases, like schizophrenia or bipolar disorder. Excessive dopaminergic tone in subcortical brain regions is associated with psychotic episodes, while reduced prefrontal dopaminergic activity is associated with impaired cognitive performance and reduced motivation, among other symptoms. Inhibitory interneurons expressing the calcium binding protein parvalbumin are particularly affected in both schizophrenia and bipolar disorder, as they set a fine-tuned physiological inhibitory/excitatory balance. Parvalbumin and somatostatin interneuron subtypes, are born from the medial ganglionic eminence and require the sequential expression of specific transcription factors for their specification, such as Nkx6.2. Here, we aimed at characterizing in detail interneuron subtypes derived from Nkx6.2 expressing progenitors by the generation of an Nkx6.2 Cre transgenic mouse line. We show that Nkx6.2 specifies over a third part of the total population of cortical somatostatin interneurons, preferentially at early developmental time points, whereas at late developmental stages, Nkx6.2 expressing progenitors shift to parvalbumin interneuron specification. Dopamine D2 receptor deletion from Nkx6.2 expressing progenitors causes abnormal phenotypes restricted to cognitive, motivation and anxiety domains. Our results show that Nkx6.2 have the potential to specify both somatostatin and parvalbumin interneurons in an opposite timed program and that DRD2 expression is required in Nkx6.2 expressing progenitors to avoid impaired phenotypes commonly associated to the pathophysiology of psychiatric diseases.

MXene‐Coated Liposome‐Quercetin‐Functionalized Gold Nanoparticles for Electrochemical Detection of Dopamine

This study reports a novel electrochemical approach for selective dopamine (DA) sensing. DA is a potential neurological biomarker for human aging and other neurodegenerative disorders, particularly Alzheimer's disease. The sensor is constructed using titanium‐based MXene and quercetin (Qu)‐loaded liposome functionalized with gold nanoparticles (AuNPs) (MXene/Lip‐Qu@AuNPs). MXene/Lip‐Qu@AuNPs is coated on a glassy carbon electrode (GCE) for DA sensing. The MXene provides high conductivity for electrochemical measurements of DA. The modified GCE is employed for DA sensing against various interferants, including ascorbic acid, aspartic acid, arginine, and cysteine. The proposed MXene/Lip‐Qu@AuNP‐based GCE exhibits sufficient detection limits of 0.35 and 0.72 μM for DA sensing using cyclic voltammetry and differential pulse voltammetry methods within a linear concentration range of 1–10 μM, respectively. The proposed sensor is used to detect DA in human serum samples. Hence, the proposed novel sensor is highly convenient and provides highly selective and sensitive DA detection.

3,5-Dihydroxybenzoic Acid-Based Selective Dopamine Detection via Subsititution-Enhanced Kinetics Differences.

The selective recognition of dopamine (DA) over other neurotransmitter analogues is difficult due to the similar molecular structure and chemical reactivity. In this study, substitution-regulated chemical reactivity of the sensing substrate is utilized to explore a novel DA detection probe with satisfying selectivity. As a case study, 3,5-dihydroxybenzoic acid (DHBA, carboxy-substituted resorcinol)-based probes have been explored for selective and ratiometric DA sensing. The carboxy substitution benefits the stabilization of the carbanion intermediate and the azamonardine product, which enhances the reaction kinetics and thermodynamics and subsequently facilitates selective DA recognition over other analogues and interferents. By exploring DHBA emission as the internal reference, ratiometric fluorescence variation is realized, which contributes to sensitive DA analysis. With the combination of logic gate and fluorometric analysis, DA detection in both low and high concentrations can be readily achieved. In addition, the DA analysis in biological samples and the enzymatic transformation of DA analogues in cerebrospinal fluid samples are achieved by the proposed DHBA probe.

Chirality Matters: Fine-Tuning of Novel Monoamine Reuptake Inhibitors Selectivity through Manipulation of Stereochemistry.

The high structural similarity, especially in transmembrane regions, of dopamine, norepinephrine, and serotonin transporters, as well as the lack of all crystal structures of human isoforms, make the specific targeting of individual transporters rather challenging. Ligand design itself is also rather limited, as many chemists, fully aware of the synthetic and analytical challenges, tend to modify lead compounds in a way that reduces the number of chiral centers and hence limits the potential chemical space of synthetic ligands. We have previously shown that increasing molecular complexity by introducing additional chiral centers ultimately leads to more selective and potent dopamine reuptake inhibitors. Herein, we significantly extend our structure-activity relationship of dopamine transporter-selective ligands and further demonstrate how stereoisomers of defined absolute configuration may fine-tune and direct the activity towards distinct targets. From the pool of active compounds, using the examples of stereoisomers 7h and 8h, we further showcase how in vitro activity significantly differs in in vivo drug efficacy experiments, calling for proper validation of individual stereoisomers in animal studies. Furthermore, by generating a large library of compounds with defined absolute configurations, we lay the groundwork for computational chemists to further optimize and rationally design specific monoamine transporter reuptake inhibitors.

Comment on: Effects of selective dopamine D3 receptor partial agonist/antagonists on oxycodone self-administration and antinociception in monkeys.

Comment on: Effects of selective dopamine D3 receptor partial agonist/antagonists on oxycodone self-administration and antinociception in monkeys.

The dopamine D1 receptor antagonist SCH-23390 blocks the acquisition, but not expression of mitragynine-induced conditioned place preference in rats

Mitragynine (MG) is the primary active constituent of Mitragyna speciosa Korth (kratom), a psychoactive Southeast Asian plant with potential therapeutic use. Numerous studies support roles of dopaminergic system in drug reward. However, the involvement of the dopaminergic system in mediating MG reward and drug-seeking is poorly understood. Using conditioned place preference (CPP) paradigm, the present study aims to evaluate the roles of the dopamine (DA) D1 receptor in the acquisition and expression of MG-induced CPP in rats. The effects of SCH-23390, a selective DA D1 receptor antagonist, on the acquisition of MG-induced CPP were first investigated. Rats were pre-treated systemically with SCH-23390 (0, 0.1 and 0.3 mg/kg, i.p.) prior to MG (10 mg/kg) conditioning sessions. Next, we tested the effects of the DA D1 receptor antagonist on the expression of MG-induced CPP. Furthermore, the effects of a MG-priming dose (5 mg/kg) on the reinstatement of extinguished CPP were tested. The results showed that SCH-23390 dose-dependently suppressed the acquisition of a MG-induced CPP. In contrast, SCH-23390 had no effect on the expression of a MG-induced CPP. The findings of this study suggested a crucial role of the DA D1 receptor in the acquisition, but not the expression of the rewarding effects of MG in a CPP test. Furthermore, blockade of the D1-like receptor during conditioning did not prevent MG priming effects on CPP reinstatement test, suggesting no role for the DA D1 receptor in reinstatement sensitivity.

Prevalence of the use of antidepressants in patients with venous thromboembolism

To estimate the prevalence of Antidepressant use in patients with a history of venous thromboembolism (VTE). Describe the patient's characteristics and which drugs are the most prescribed. A cross-sectional study involving a consecutive sample of patients included in the Registro de Enfermedad Tromboembólica (RIET) from the Hospital Italiano de Buenos Aires in a period between 01/01/2014 to 01/09/2018. All patients presented symptomatic VTE and confirmed diagnosis. Drugs considered included in this study were: Selective Serotonin Reuptake Inhibitors (SSRI), Dopamine and Norepinephrine Reuptake Inhibitors (NDRI), Serotonin and Norepinephrine Reuptake Inhibitors (SNRI) and Tricyclic antidepressants (TCA). From a total of 2373 patients with VTE, 472 were active users of antidepressants, showing a prevalence of antidepressant use of 19.9% (CI 95%). The most frequently prescribed drugs by drug classification were: SSRI 83.9%, TCA 20.5%, ISRN 14.6%, and NDRI 2.5%. Patients presented a median age of 76 years, predominantly women (71.4%), with several comorbidities: 52.24% arterial hypertension, 37.29% overweight, and 34.75% history of smoking. Concerning relevant history, we observed: 29.03% active oncologic disease, 26.27% major surgery before the VTE, and 21.61% previous VTE. The prevalence of antidepressant use in patients with VTE is 19.9%, superior by far to that of the general population. Depression is a major cause of morbidity worldwide, and its prevalence is increasing over the years.

Discovery of Selective Dopamine Receptor Ligands Derived from (-)-Stepholidine via C-3 Alkoxylation and C-3/C-9 Dialkoxylation.

We evaluated C-3 alkoxylated and C-3/C-9 dialkoxylated (-)-stepholidine analogues to probe the tolerance at the C-3 and C-9 positions of the tetrahydroprotoberberine (THPB) template toward affinity for dopamine receptors. A C-9 ethoxyl substituent appears optimal for D1R affinity since high D1R affinities were observed for compounds that contain an ethyl group at C-9, with larger C-9 substituents tending to decrease D1R affinity. A number of novel ligands were identified, such as compounds 12a and 12b, with nanomolar affinities for D1R and no affinity for either D2R or D3R, with compound 12a being identified as a D1R antagonist for both G-protein- and β-arrestin-based signaling. Compound 23b was identified as the most potent and selective D3R ligand containing a THPB template to date and functions as an antagonist for both G-protein- and β-arrestin-based signaling. Molecular docking and molecular dynamics studies validated the D1R and D3R affinity and selectivity of 12a, 12b, and 23b.

A Sensitive and Selective Non-Enzymatic Dopamine Sensor Based on Nanostructured Co3O4–Fe2O3 Heterojunctions

In the present work, a study was carried out with the aim of enhancing the performance of electrochemical biosensors based on Co3O4:Fe2O3 heterojunctions. Specifically, the redox behavior of screen–printed carbon electrodes (SPCEs) modified with Co3O4:Fe2O3 (0.5 wt%:x wt%) nanocomposites, where x ranged from 0.1 to 0.5 wt%, was examined in detail. The hybrid nanocomposites were synthesized using the sol-gel auto-combustion method. Several characterization methods were performed to investigate the morphology, microstructure, and surface area of the pure Co3O4, pure Fe2O3, and the synthesized Co3O4:Fe2O3 nanocomposites. Using cyclic voltammetry (CV) tests, the electrochemical behavior of the modified electrodes toward the dopamine (DA) molecules was investigated. The modified Co3O4:Fe2O3, (0.5 wt%, x = 0.4 wt%)/SPCE resulted in a sensor with the best electrochemical performance toward DA. A high linear relationship between DA concentrations and the faradic current variation (ipa (μA) = 0.0736 + 0.1031 CDA (μA) and R2 = 0.99) was found in the range of 10–100 μM. The sensitivity value was computed to be 0.604 µA µM−1cm−2 and the limit of detection (LOD) 0.24 µM. Based on the characterization and electrochemical results, it can be suggested that the formation of Co3O4:Fe2O3 heterostructures provides a large specific surface area, an increased number of electroactive sites at the metal oxide interface and a p–n heterojunction, thus ensuring a remarkable enhancement in the electrochemical response towards DA.

Melamine-Based Nanocomposites for Selective Dopamine and Uric Acid Sensing

The formation process of carbon dots (CDs) is mostly polymerization; recently, studies on the polymerization of carbon families (graphene oxide and C60) have been receiving exciting attention. Herein, a protocol of prepolymerization and electropolymerization of monomer (melamine) and nanomonomer (CDs fixed melamine residues) was proposed to prepare a nanocomposite for selective dopamine (DA) and uric acid (UA) sensing. The nanomonomer was prepared by hydrothermal prepolymerization of melamine, and then the nanocomposite was formed in situ by electropolymerization of the CDs/carboxylated multiwalled carbon nanotubes (MWCNTs-COOH)-modified glassy carbon electrode (GCE) in KCl solution. Scanning electron microscopy, transmission electron microscopy, energy-dispersive spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry were used to characterize the properties of the nanocomposite. Under optimal conditions, the electrochemical sensor shows selectivity and a wide linear range from 0.1 to 10 μM for DA and 0.1 to 200 μM for UA, with the detection limit of 0.023 and 0.064 μM (S/N = 3) in the presence of AA, respectively. In addition, the proposed sensor was also applied to selectively test DA and UA in the presence of 500 μmol/L AA in real samples with satisfactory recovery.

Classifying migraine using PET compressive big data analytics of brain's μ-opioid and D2/D3 dopamine neurotransmission.

Introduction: Migraine is a common and debilitating pain disorder associated with dysfunction of the central nervous system. Advanced magnetic resonance imaging (MRI) studies have reported relevant pathophysiologic states in migraine. However, its molecular mechanistic processes are still poorly understood in vivo. This study examined migraine patients with a novel machine learning (ML) method based on their central μ-opioid and dopamine D2/D3 profiles, the most critical neurotransmitters in the brain for pain perception and its cognitive-motivational interface. Methods: We employed compressive Big Data Analytics (CBDA) to identify migraineurs and healthy controls (HC) in a large positron emission tomography (PET) dataset. 198 PET volumes were obtained from 38 migraineurs and 23 HC during rest and thermal pain challenge. 61 subjects were scanned with the selective μ-opioid receptor (μOR) radiotracer [11C]Carfentanil, and 22 with the selective dopamine D2/D3 receptor (DOR) radiotracer [11C]Raclopride. PET scans were recast into a 1D array of 510,340 voxels with spatial and intensity filtering of non-displaceable binding potential (BPND), representing the receptor availability level. We then performed data reduction and CBDA to power rank the predictive brain voxels. Results: CBDA classified migraineurs from HC with accuracy, sensitivity, and specificity above 90% for whole-brain and region-of-interest (ROI) analyses. The most predictive ROIs for μOR were the insula (anterior), thalamus (pulvinar, medial-dorsal, and ventral lateral/posterior nuclei), and the putamen. The latter, putamen (anterior), was also the most predictive for migraine regarding DOR D2/D3 BPND levels. Discussion: CBDA of endogenous μ-opioid and D2/D3 dopamine dysfunctions in the brain can accurately identify a migraine patient based on their receptor availability across key sensory, motor, and motivational processing regions. Our ML-based findings in the migraineur's brain neurotransmission partly explain the severe impact of migraine suffering and associated neuropsychiatric comorbidities.

A Novel Polyurethane-Based Polyion Complex Material with Tunable Selectivity against Interferents for Selective Dopamine Determination

Polyion complex (PIC) materials have been widely used in biosensors due to their molecular selectivity. However, achieving both widely controllable molecular selectivity and long-term solution stability with traditional PIC materials has been challenging due to the different molecular structures of polycations (poly-C) and polyanions (poly-A). To address this issue, we propose a novel polyurethane (PU)-based PIC material in which the main chains of both poly-A and poly-C are composed of PU structures. In this study, we electrochemically detect dopamine (DA) as the analyte and L-ascorbic acid (AA) and uric acid (UA) as the interferents to evaluate the selective property of our material. The results show that AA and UA are significantly eliminated, while DA can be detected with a high sensitivity and selectivity. Moreover, we successfully tune the sensitivity and selectivity by changing the poly-A and poly-C ratios and adding nonionic polyurethane. These excellent results were employed in the development of a highly selective DA biosensor with a detection range from 500 nM to 100 μM and a 3.4 μM detection limit. Overall, our novel PIC-modified electrode has the potential to advance biosensing technologies for molecular detection.

Release of 6-nitrodopamine from human popliteal artery and vein

6-Nitrodopamine (6-ND) is a novel catecholamine that is released from human umbilical cord vessels, and it causes vascular relaxation by acting as a dopamine D2-receptor antagonist. Here it was investigated whether human peripheral vessels obtained from patients who have undergone surgery for leg amputation release 6-ND, and its action in these tissues. Popliteal artery and vein strips present basal release of 6-ND, as measured by liquid chromatography coupled to tandem mass spectrometry. The release was significantly reduced when the tissues were pre-treated with the nitric oxide synthase inhibitor L-NAME (100 μM), or when the endothelium was mechanically removed. In U-46619 (3 nM) pre-contracted rings, 6-ND induced concentration-dependent relaxations (pEC50 8.18 ± 0.05 and 8.40 ± 0.08, in artery and vein rings, respectively). The concentration-dependent relaxations induced by 6-ND were unaffected in tissues pre-treated with L-NAME, but significantly reduced in tissues where the endothelium has been mechanically removed. In U-46619 (3 nM) pre-contracted rings, the selective dopamine D2 receptor antagonist L-741,626 also caused concentration-dependent relaxations (pEC50 8.92 ± 0.22 and 8.79 ± 0.19, in artery and vein rings, respectively). The concentration-dependent relaxations induced by L-741,626 were unaffected in tissues pre-treated with L-NAME, but significantly reduced in tissues where the endothelium has been mechanically removed. This is the first demonstration that 6-nitrodopamine is released from human peripheral artery and vein rings. The results also indicate that endothelium-derived dopamine is a major contractile agent in the popliteal artery and vein, and that selective dopamine D2-receptor antagonists such as 6-ND, may have therapeutic potential in the treatment of human peripheral vascular diseases.

Differential effects of dopamine receptor agonists ropinirole and quinpirole on locomotor and anxiolytic behaviors in larval zebrafish (Danio rerio): A role for the GABAergic and glutamate system?

Zebrafish are frequently used as a vertebrate model to elucidate toxicological and pharmacological mechanisms of action in the central nervous system. Pharmacological studies demonstrate that dopamine, signaling via several receptor subtypes, regulates zebrafish larval behavior. Quinpirole is a selective dopamine receptor agonist for D2 and D3 subtypes while ropinirole exhibits selectivity toward D2, D3, and D4 receptors. The main objective of this study was to determine the short-term actions of quinpirole and ropinirole on the locomotor activity and anxiolytic/anti-anxiolytic behaviors of zebrafish. Furthermore, dopamine signaling can cross talk with other neurotransmitter systems, including the GABAergic and glutamatergic system. As such, we measured transcriptional responses in these systems to determine whether dopamine receptor activation modulated GABAergic and glutaminergic systems. Ropinirole reduced locomotor activity of larval fish at concentrations of 1 μM and greater but quinpirole did not affect locomotor activity at all concentrations tested. Anxiolytic-related behaviors were also compared between the two pharmaceuticals. Noteworthy was that both dopamine receptor agonists at 1 μM increased the activity of zebrafish in the light phase of a light-dark preference test, which may be related to the activation of D2 and/or D3 receptors. In terms of interactions with other neurotransmitter systems, ropinirole up-regulated transcripts in larvae zebrafish related to both the GABAergic and glutamatergic systems (abat, gabra1, gabrb1, gad1b, gabra5, gabrg3, and grin1b). Conversely, quinpirole did not alter the abundance of any transcript measured, suggesting that dopamine-GABA interaction may involve D4-receptors, which has been noted in mammalian models. This study demonstrates pleiotropic actions of dopamine agonism on the GABA and glutamate system in larval zebrafish. This study has relevance for characterizing toxicants that act via dopamine receptors and for elucidating mechanisms of neurological disorders that involve motor circuits and multiple neurotransmitter systems, like Parkinson's disease.

Optofluidic laser sensor for the detection of dopamine

Dopamine (DA) is a biomarker of many psychiatric diseases, such as schizophrenia and Parkinson's disease. Most current DA detection research adopts electrochemical method, which suffers interferences caused by many analogs with similar structures or redox potentials. To realize highly sensitive and selective DA sensing, herein we propose an optofluidic-laser-based DA sensor. Via the competitive adsorption mechanism, rhodamine 6G (Rh6G) is fixed on graphene oxide (GO) and replaced by DA in the sample, with the re-excited Rh6G serving as the gain medium of the optofluidic laser. As the DA concentration increases, more Rh6G is released into the sample, which induces an increase in the relative slope efficiency of the optofluidic laser and a reduction in the laser threshold. Both the relative slope efficiency and threshold attain a suitable linear relationship with the DA concentration within the 5–800 μM range. Under ideal circumstances, the detection limit of the biosensor is 0.3 µM. Moreover, the optofluidic laser-based biosensor achieves favorable selectivity for DA detection, proving the advantages of using optical laser sensors for DA detection in complex samples.

Mental Illness: Social Dimension, is it Being Systematically Ignored?

For nearly half a century, the predominant focus of research in mental health has been on understanding the biological basis of mental disorders and new drugs. This was a major shift from the first half of the 20th century, when the psychoanalytic model was dominating the scene. Our understanding of the biological basis of many mental disorders has definitely improved in the last few decades with the advances in structural and functional imaging. However, there has not been any major advancement on the therapeutic side, with no significant introductions after the selective serotonin reuptake inhibitors and serotonin dopamine antagonists. Mental disorders have been identified as an important contributor to the global burden of disease, with the burden not shown any fall over the last 3 decades. Thus, there is a need to focus on the social dimension of mental disorders which has been systematically ignored. The strategies may include following a public health approach, dealing with stigma associated with mental disorders, strengthening the mental health services in the community, and improving their accessibility, and promotion of mental health well-being, dealing with disease burden, building resilience, involving families in management, targeting recovery, social prescribing, and using information technology, wherever appropriate.