Dopamine Response Research Articles

Stress-induced cortical dopamine response is altered in subjects at clinical high risk for psychosis using cannabis.

Stress and cannabis use are risk factors for the development of psychosis. We have previously shown that subjects at clinical high risk for psychosis (CHR) exhibit a higher striatal dopamine response to stress compared with healthy volunteers (HV), with chronic cannabis use blunting this response. However, it is unknown if this abnormal dopamine response extends to the prefrontal cortex (PFC). Here, we investigated dorsolateral PFC (dlPFC) and medial PFC (mPFC) dopamine release using [11 C]FLB457 positron emission tomography (PET) and a validated stress task. Thirty-three participants completed two PET scans (14 CHR without cannabis use, eight CHR regular cannabis users [CHR-CUs] and 11 HV) while performing a Sensory Motor Control Task (control scan) and the Montreal Imaging Stress Task (stress scan). Stress-induced dopamine release (ΔBPND ) was defined as percent change in D2/3 receptor binding potential between both scans using a novel correction for injected mass of [11 C]FLB457. ΔBPND was significantly different between groups in mPFC (F(2,30) = 5.40, .010), with CHR-CUs exhibiting lower ΔBPND compared with CHR (.008). Similarly, salivary cortisol response (ΔAUCI ) was significantly lower in CHR-CU compared with CHR (F(2,29) = 5.08, .013; post hoc .018) and positively associated with ΔBPND . Furthermore, CHR-CUs had higher attenuated psychotic symptoms than CHR following the stress task, which were negatively associated with ΔBPND . Length of cannabis use was negatively associated with ΔBPND in mPFC when controlling for current cannabis use. Given the global trend to legalize cannabis, this study is important as it highlights the effects of regular cannabis use on cortical dopamine function in high-risk youth.

Impacts of inter-trial interval duration on a computational model of sign-tracking vs. goal-tracking behaviour

In the context of Pavlovian conditioning, two types of behaviour may emerge within the population (Flagel et al. Nature, 469(7328): 53–57, 2011). Animals may choose to engage either with the conditioned stimulus (CS), a behaviour known as sign-tracking (ST) which is sensitive to dopamine inhibition for its acquisition, or with the food cup in which the reward or unconditioned stimulus (US) will eventually be delivered, a behaviour known as goal-tracking (GT) which is dependent on dopamine for its expression only. Previous work by Lesaint et al. (PLoS Comput Biol, 10(2), 2014) offered a computational explanation for these phenomena and led to the prediction that varying the duration of the inter-trial interval (ITI) would change the relative ST-GT proportion in the population as well as phasic dopamine responses. A recent study verified this prediction, but also found a rich variance of ST and GT behaviours within the trial which goes beyond the original computational model. In this paper, we provide a computational perspective on these novel results.

Vesicular Antipsychotic Drug Release Evokes an Extra Phase of Dopamine Transmission.

Many psychiatric drugs are weak bases that accumulate in and are released from synaptic vesicles, but the functional impact of vesicular drug release is largely unknown. Here, we examine the effect of vesicular release of the anxiolytic antipsychotic drug cyamemazine on electrically evoked striatal dopamine responses with fast scan cyclic voltammetry. Remarkably, in the presence of nanomolar extracellular cyamemazine, vesicular cyamemazine release in the brain slice can increase dopamine responses 30-fold. Kinetic analysis and multiple stimulation experiments show that this occurs by inducing delayed emptying of the releasable dopamine pool. Also consistent with increased dopamine release, an antagonist (dihydro-β-erythroidine) implicates nicotinic acetylcholine receptors, which can directly cause dopamine release, in the vesicular cyamemazine effect. Therefore, vesicular release of cyamemazine can dramatically enhance dopaminergic synaptic transmission, possibly by recruiting an excitatory cholinergic input to induce an extra phase of release. More generally, this study suggests that synaptic drug release following vesicular accumulation by acidic trapping can expand psychiatric drug pharmacodynamics.

Role of genetic background in the effects of adolescent nicotine exposure on mesolimbic dopamine transmission.

Smoking during adolescence may increase the likelihood to develop nicotine dependence and to abuse other drugs such as cocaine. Despite great efforts to understand underlying neurobiological mechanisms of this progression, less attention has been paid to the role of genetic factors. Here, we investigated the influence of both genetic background and age at first nicotine exposure in the long-lasting effects on mesolimbic dopamine transmission including the increased cocaine-rewarding effect. Mid-adolescent and adult rats of inbred strains Lewis (addiction prone) and Fischer 344 (addiction resistant) were administered nicotine (0.4 mg/kg) or vehicle once daily for 5 days. Changes in dopamine transmission were investigated by in vivo microdialysis and electrophysiology after 30 days of withdrawal, whereas changes in cocaine-rewarding effect were assessed via conditioned place preference paradigm. Nicotine pre-exposure differentially changed mesolimbic dopamine transmission depending on strain and age of pre-exposure. A potentiation of dopamine response to nicotine was observed in nucleus accumbens (NAc) core of both strains and age groups, whereas dopamine response in NAc shell was enhanced exclusively in Lewis rats exposed to nicotine during adolescence. A similar response was observed following cocaine challenge at adulthood. Changes in VTA dopamine cell population and activity were observed only in adolescent nicotine-pretreated Lewis rats, which also showed an increased cocaine-rewarding effect at adulthood. These results highlight the influence of genetic background in the long-lasting effects of nicotine exposure and suggest that exposure during adolescence might increase nicotine and cocaine-rewarding properties in genetically vulnerable individuals, thereby facilitating progression toward dependence.

A Novel Enzyme-Free Biosensor Based on Porous Core-Shell Metal Organic Frame Nanocomposites Modified Electrode for Highly Sensitive Detection of Uric Acid and Dopamine.

A novel enzyme-free biosensor based on porous metal organic frame nanocomposites, i.e., core-shell structured Au@NC@GC nanocomposites, has been constructed for simultaneous determination of uric acid (UA) and dopamine (DA). Au@ZIF-8@ZIF-67 was prepared through a seed-mediated growth method and carbonized in nitrogen atmosphere to synthesize a nanoporous hybrid carbon materials (Au@NC@GC). Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) studies demonstrate that the as-prepared Au@NC@GC modified glassy carbon electrode (Au@NC@GC-GCE) possesses a high selectivity and sensitivity for simultaneous detections of UA and DA. It exhibited wide linear responses for UA and DA in the range from 10 μM to 600 μM and 10 μM to 150 μM, with the detection limits of 0.773 nM and 0.746 nM, respectively (S/N = 3). Moreover, this novel electrochemical biosensor could be further utilized in biological analysis (i.e., human serum), and the satisfactory recovery results of UA and DA could be readily obtained. These afore-mentioned results further manifest that the as-prepared biosensors are capable for quantitatively monitoring UA and DA in serum, verifying the possibility for its future promising applications in real biological or clinic samples analysis.

Buprenorphine prevents stress-induced blunting of nucleus accumbens dopamine response and approach behavior to food reward in mice

Alterations to the mesolimbic dopamine (DA) system are thought to underlie dysfunctional reward processing in stress-related psychiatric disorders. Using in vivio microdialysis in awake freely moving mice, we assessed the effects of stress on the motivational and neurochemical correlates underlying conditioned approach behavior for palatable food in the non-deprived mouse. Mice trained to approach and consume food in a familiar environment exhibited a 30% increase in nucleus accumbens shell (AcbSh) extracellular dopamine levels coincident with approach towards and consumption of the food reward. This effect was not observed in mice that were presented with the food in an unfamiliar environment or were exposed for the first time and were region specific. The addition of an acute environmental stressor (bright light and novel scent) during food exposure decreased DA release and delayed approach to the food. The disruptive impact of acute novelty stress on DA levels and approach behavior was reversed in animals pretreated with buprenorphine, an opioid drug with antidepressant-like and anxiolytic effects. Together, these data indicate that exposure to mild stress reduces incentive drive to approach palatable food via alterations in AcbSh dopamine responsiveness to food reward. Moreover, they implicate the brain opioid system as a potential pharmacological target for counteracting behavioral and neurochemical elements associated with stress.

Morphology-Dependent Electrochemical Sensing Properties of Iron Oxide-Graphene Oxide Nanohybrids for Dopamine and Uric Acid.

Various morphologies of iron oxide nanoparticles (Fe2O3 NPs), including cubic, thorhombic and discal shapes were synthesized by a facile meta-ion mediated hydrothermal route. To further improve the electrochemical sensing properties, discal Fe2O3 NPs with the highest electrocatalytic activity were coupled with graphene oxide (GO) nanosheets. The surface morphology, microstructures and electrochemical properties of the obtained Fe2O3 NPs and Fe2O3/GO nanohybrids were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. As expected, the electrochemical performances were found to be highly related to morphology. The discal Fe2O3 NPs coupled with GO showed remarkable electrocatalytic activity toward the oxidation of dopamine (DA) and uric acid (UA), due to their excellent synergistic effect. The electrochemical responses of both DA and UA were linear to their concentrations in the ranges of 0.02–10 μM and 10–100 μM, with very low limits of detection (LOD) of 3.2 nM and 2.5 nM for DA and UA, respectively. Moreover, the d-Fe2O3/GO nanohybrids showed good selectivity and reproducibility. The proposed d-Fe2O3/GO/GCE realized the simultaneous detection of DA and UA in human serum and urine samples with satisfactory recoveries.

Electrocatalytic oxidation toward dopamine and acetaminophen based on AuNPs@TCnA/GN modified glassy carbon electrode

In this paper, gold nanoparticles (AuNPs) modified by thiolated calix[n]arene (TCnA, n = 4, 6, 8) were anchored on graphene nanosheets (GN) by π-π stacking interaction between TCnA molecules and GN. Testing of various electrochemical techniques display that the AuNPs@TCnA/GN modified glass carbon electrodes (GCE) show good electrocatalytic property, molecular recognition and enrichment performance toward dopamine (DA) and acetaminophen (AC), and exhibit high current response. In all of modified electrodes, AuNPs@TC8A/GN/GCE shows an outstanding electrochemical response for DA and AC with high sensitivity of 5.08 and 9.76 mA mmol−1 L cm−2, respectively. The analytical curves for DA obtained by differential pulse voltammetry (DPV) are linear in the range from 0.5 to 150 μM and from 0.3 to 1.0 mM. The linear range for AC obtained by DPV is from 0.5 to 120 μM. Besides, AuNPs@TC8A/GN/GCE can be applied to determinate of DA and AC simultaneously, implying the prospect to develop a dual sensor under the same construction platform.

Gold Nanoparticle Modified Carbon Fiber Microelectrodes for Enhanced Neurochemical Detection.

For over 30 years, carbon-fiber microelectrodes (CFMEs) have been the standard for neurotransmitter detection. Generally, carbon fibers are aspirated into glass capillaries, pulled to a fine taper, and then sealed using an epoxy to create electrode materials that are used for fast scan cyclic voltammetry testing. The use of bare CFMEs has several limitations, though. First and foremost, the carbon fiber contains mostly basal plane carbon, which has a relatively low surface area and yields lower sensitivities than other nanomaterials. Furthermore, the graphitic carbon is limited by its temporal resolution, and its relatively low conductivity. Lastly, neurochemicals and macromolecules have been known to foul at the surface of carbon electrodes where they form non-conductive polymers that block further neurotransmitter adsorption. For this study, we modify CFMEs with gold nanoparticles to enhance neurochemical testing with fast scan cyclic voltammetry. Au3+ was electrodeposited or dipcoated from a colloidal solution onto the surface of CFMEs. Since gold is a stable and relatively inert metal, it is an ideal electrode material for analytical measurements of neurochemicals. Gold nanoparticle modified (AuNP-CFMEs) had a stability to dopamine response for over 4 h. Moreover, AuNP-CFMEs exhibit an increased sensitivity (higher peak oxidative current of the cyclic voltammograms) and faster electron transfer kinetics (lower ΔEP or peak separation) than bare unmodified CFMEs. The development of AuNP-CFMEs provides the creation of novel electrochemical sensors for detecting fast changes in dopamine concentration and other neurochemicals at lower limits of detection. This work has vast applications for the enhancement of neurochemical measurements. The generation of gold nanoparticle modified CFMEs will be vitally important for the development of novel electrode sensors to detect neurotransmitters in vivo in rodent and other models to study neurochemical effects of drug abuse, depression, stroke, ischemia, and other behavioral and disease states.

The selective electrochemical detection of dopamine in the presence of ascorbic acid and uric acid using electro-polymerised-β-cyclodextrin incorporated f-MWCNTs/polyaniline modified glassy carbon electrode

The present work describes a differential pulse voltammetric determination of dopamine (DA) using a glassy carbon electrode (GCE) modified with poly-beta-cyclodextrin incorporated with oxidised (OH) multi-walled carbon nanotubes (poly-β-CD(f-MWCNTs) and anion-doped polyaniline (PANI) composite. The poly-β-CD(f-MWCNTs)/PANI composite modified electrode was prepared by electropolymerisation of β-CD(f-MWCNTs) on anion-doped polyaniline by scanning repetitively in the phosphate buffer solution (pH 7) from −2.0 to 2.5 V. The as-prepared poly-β-CD(f-MWCNTs)/PANI composite was characterized by scanning electron microscopy, transmission electron microscopy, electrochemical impedance spectroscopy and Fourier transform infrared spectroscopy. The composite presented excellent synergistic effect and shows an enhanced catalytic activity than electrodes modified with poly-β-CD and PANI. In comparison to the CV results of bare GC and modified GCE, the large electrochemical potential difference has achieved via the used of the poly-β-CD(f-MWCNTs)/PANI composite to distinguish the DA from AA and UA with peak-to-peak separations recorded at 244 mV (AA-DA) and 135 mV (DA-UA). Under optimum conditions, differential pulse voltammetric was used to determine the DA, and the voltammetric response of DA was linear over the concentration ranging from 2 μmol L−1 to 24 μmol L−1 with low detection limit (LOD) of 0.0164 μmol L−1 (S/N = 3) and high sensitivity of 26.79 μA μM−1 cm−2. The poly-β-CD(f-MWCNTs)/PANI composite modified electrode exhibits high selectivity in the presence range of potentially interfering uric acid and ascorbic acid even in high concentration. As a proof of concept, the practicality of the sensors was examined in human urine samples, and shows acceptable practicality for the determination of DA.

175. Targeting the Gut-Brain Axis to Regulate Preference and Striatal Response to Fat

High fat diet (HFD) leads to disrupted striatal dopamine function and alterations in fat preference. One mechanism by which this occurs is depletion of gut lipid messengers, including oleoylethanolamine (OEA), which when replenished rescues dopamine response and increases preference for low fat emulsions via the generation of vagal afferent signals (Tellez et al., 2013). Using a supplement containing the OEA precurser N-oleyl-phosphatidylethanolamine and epigallocatechin-3-gallate (NOPE+EGCG), we tested whether this effect translates to humans and whether supplementation improves outcomes on a behavioral weight loss trial.

138. Stress-Induced Prefrontocortical Dopamine Response is Altered in Subjects at Clinical High Risk for Psychosis Using Cannabis

138. Stress-Induced Prefrontocortical Dopamine Response is Altered in Subjects at Clinical High Risk for Psychosis Using Cannabis

Rapid response of dopamine towards insitu synthesised copper nanocluster in presence of H2O2

Rapid and real-time monitoring of catecholamine neurotransmitter dopamine receives immense importance since it plays a crucial role as a local chemical messenger for interneuronal communications in mammalian central and peripheral nervous systems. In the present study, blue emitting copper nanocluster was synthesized in presence (BSA CuNC1) and absence (BSA CuNC2) of hydrogen peroxide and fluorescence response of the two systems towards dopamine was analysed. At an excitation of 355 nm, fast response towards dopamine detection was obtained for BSA CuNC1 system having limit of detection 0.1637 pM. The fast interaction of dopamine with BSA CuNC1 can be attributed to the intrinsic peroxidase like activity of CuNC in presence of H2O2. On the other hand, the response of dopamine towards BSA CuNC2 was very slow with a limit of detection 0.024 nM. Encouraged by the fast response and low limit of detection, the BSA CuNC1 system was effectively applied for dopamine detection in real sample matrices. The recovery percentage for serum sample obtained was in the range 90–98.33% and for urine sample was in the range 89–96.66%. In addition to that, a paper test strips using BSA CuNC1 was developed which exhibited colour change as well as fluorescence quenching, creates a low cost approach for the fast monitoring of dopamine.

Expected Reward Value and Reward Uncertainty Have Temporally Dissociable Effects on Memory Formation.

Anticipating rewards has been shown to enhance memory formation. Although substantial evidence implicates dopamine in this behavioral effect, the precise mechanisms remain ambiguous. Because dopamine nuclei have been associated with two distinct physiological signatures of reward prediction, we hypothesized two dissociable effects on memory formation. These two signatures are a phasic dopamine response immediately following a reward cue that encodes its expected value and a sustained, ramping response that has been demonstrated during high reward uncertainty [Fiorillo, C. D., Tobler, P. N., & Schultz, W. Discrete coding of reward probability and uncertainty by dopamine neurons. Science, 299, 1898-1902, 2003]. Here, we show in humans that the impact of reward anticipation on memory for an event depends on its timing relative to these physiological signatures. By manipulating reward probability (100%, 50%, or 0%) and the timing of the event to be encoded (just after the reward cue versus just before expected reward outcome), we demonstrated the predicted double dissociation: Early during reward anticipation, memory formation was improved by increased expected reward value, whereas late during reward anticipation, memory formation was enhanced by reward uncertainty. Notably, although the memory benefits of high expected reward in the early interval were consolidation dependent, the memory benefits of high uncertainty in the later interval were not. These findings support the view that expected reward benefits memory consolidation via phasic dopamine release. The novel finding of a distinct memory enhancement, temporally consistent with sustained anticipatory dopamine release, points toward new mechanisms of memory modulation by reward now ripe for further investigation.

Postsynaptic Mechanisms Render Syn I/II/III Mice Highly Responsive to Psychostimulants.

BackgroundSynapsins are encoded by SYN I, SYN II, and SYN III, and they regulate neurotransmitter release by maintaining a reserve pool of synaptic vesicles.MethodsPresynaptic dopamine responses to cocaine were examined by microdialysis, and postsynaptic responses were evaluated to various dopamine receptor agonists in the open field with SynI/SynII/SynIII triple knockout mice.ResultsTriple knockout mice showed enhanced spontaneous locomotion in a novel environment and were hyper-responsive to indirect and direct D1 and D2 dopamine agonists. Triple knockout animals appeared sensitized to cocaine upon first open field exposure; sensitization developed across days in wild-type controls. When mutants were preexposed to a novel environment before injection, cocaine-stimulated locomotion was reduced and behavioral sensitization retarded. Baseline dopamine turnover was enhanced in mutants and novel open field exposure increased their striatal dopamine synthesis rates. As KCl-depolarization stimulated comparable dopamine release in both genotypes, their readily releasable pools appeared indistinguishable. Similarly, cocaine-induced hyperlocomotion was indifferent to blockade of newly synthesized dopamine and depletion of releasable dopamine pools. Extracellular dopamine release was similar in wild-type and triple knockout mice preexposed to the open field and given cocaine or placed immediately into the arena following injection. Since motor effects to novelty and psychostimulants depend upon frontocortical-striatal inputs, we inhibited triple knockout medial frontal cortex with GABA agonists. Locomotion was transiently increased in cocaine-injected mutants, while their supersensitive cocaine response to novelty was lost.ConclusionsThese results reveal presynaptic dopamine release is not indicative of agonist-induced triple knockout hyperlocomotion. Instead, their novelty response occurs primarily through postsynaptic mechanisms and network effects.

Taurine Protects Against the Neurotoxic Effects of Manganese on the Dopaminergic Control of Lateral Cell Membrane Potential and Ciliary Response in Gill of Crassostrea virginica

Manganese is a neurotoxin causing manganism, a Parkinson's‐like disease involving disruption of dopaminergic neurotransmission. The mechanism by which manganese produces this dysfunction is not fully resolved. Unlike Parkinson's disease, reports postulate that manganese neurotoxicity is more likely related to downstream neuronal pathways rather than deficits in nigrostriatal function. Lack of effective treatment for manganism has been a major obstacle in its clinical management. The cilia of lateral cell in gill of Crassostrea virginica are controlled by serotonergic‐dopaminergic innervations from their ganglia. Dopamine (DA) hyperpolarizes the cell and causes cilio‐inhibition, while serotonin depolarizes and causes cilio‐excitation. Previous work of our lab showed acute and short‐term manganese treatments blocked the cilio‐inhibitory effect of DA. This neurotoxic action of manganese could be prevented by the drug p‐aminosalicylic acid or by taurine, an amino acid with efficacy in other neurodegenerative disorders. In this study we hypothesize that taurine would effectively prevent the toxic actions of manganese on both dopaminergic membrane hyperpolarization and lateral cilia inhibition. To test this we conducted acute experiments on DA dose responses (10−6 – 10−3 M) of manganese treated excised gill in the presence or absence of taurine. Ciliary activity of gill lateral cells was measured by stroboscopic microscopy and expressed as beats/min ± sem. Cell membrane potentials were simultaneously measured using the fluorescent dye DiBAC4(3). In control gill, the lateral cells responded normally to the DA dose response showing the appropriate decrease in cilia beating rates and membrane hyperpolarization. Gills treated with manganese (2 × 10−4M) had a disrupted DA response, cilio‐inhibition was impaired and the membrane did not hyperpolarize. Taurine treatment (2 × 10−4M) effectively prevented these neurotoxic effects in manganese treated gill. This physiological study in C. virginica shows that manganese disrupts the dopaminergic post‐synaptic response of lateral cells preventing membrane hyperpolarization as well disrupting cilio‐inhibition, and that taurine effectively blocked these neurotoxic actions. These findings are helpful in furthering the understanding of the mechanism of manganese neurotoxicity and provides evidence suggesting taurine be further investigated as a potential therapeutic agent for manganism.Support or Funding InformationThis work was supported in part by grant 2R25GM06003 of the Bridge Program of NIGMS, NIH grant K12GM093854‐07A1 IRACDA Program of Rutgers University and 604060048 of PSC‐CUNY.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Role of Phospholipase C in the Dopamine D2 Signaling Pathway in the Control of Lateral Cilia in Gill of Crassostrea virginica

Lateral cell cilia of gill of Crassostrea virginica are controlled by serotonergic‐dopaminergic innervations from their ganglia. Dopamine is the neurotransmitter causing cilio‐inhibition, serotonin cilio‐excitation. Previous work of our lab showed the post‐synaptic dopamine receptors present in lateral cells are D2‐type. Dopamine D2 receptors (D2R) are G protein‐coupled metabotropic receptors. Ligand binding to D2R splits its Gi/o protein into the Gβγ and Gαi/o subunits. Gαi/o inhibits adenylyl cyclase; while Gβγ opens GIRK channels, closes L‐type Ca2+ channels and activates phospholipase C (PLC). The inhibition of adenylyl cyclase and subsequent lowering of cAMP is known to slow lateral cilia; however, the role of PLC in the signaling pathway has not been well studied with respect to control of lateral cilia. Using immunohistofluorescence, our lab visualized PLC in lateral cell. In this study we hypothesized that the PLC component of the D2 pathway also plays a role in the cilio‐inhibition. To test this we utilized PLC activators and inhibitors on excised gill to determine their effects on lateral cilia. Cilia beating rates were measured using stroboscopic microscopy. In control gill, applying a dose response of dopamine (10−6 – 10−3M) is cilio‐inhibitory, decreasing beating rates of lateral cilia to 0. Applying m‐3M3FBS (10−5 – 10−4M), a PLC activator, caused a moderate decrease in cilia beating rates. Applying U73122 (10−4M), a phosphatidylinositol 4,5‐bisphosphate specific PLC inhibitor, did not alter cilia beating rates by itself, but did effect the dose response to dopamine (10−5 – 10−3M). In the presence of the inhibitor, while the 10−5M dose of dopamine caused the expected decrease in cilia beating rates, the addition of higher doses of dopamine was unable to reduce beating rates any further. As expected, the drug D609, a PLC inhibitor but specific for phosphatidylcholine, had no effects on cilia beating rates or the actions of dopamine. The results of this study supports our hypothesis that the PLC component of the D2R signal transduction pathway plays a role in the inhibitory control of gill lateral cilia. The results show that both components of the D2R pathway, the adenylyl cyclase component and the PLC component are involved in controlling lateral cilia beating. In humans the D2R signal transduction pathway is significantly involved in the actions of antidepressants, neuroleptics, and drugs of abuse, as well as implicated in neuropsychiatric and neurodegenerative disorders. This physiology study is helpful in furthering the understanding of the pathway and should help to generate further investigations.Support or Funding InformationThis work was supported in part by grant 2R25GM06003 of the Bridge Program of NIGMS, NIH grant K12GM093854‐07A1 IRACDA Program of Rutgers University and 604060048 of PSC‐CUNY.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hematite-thermally reduced graphite oxide composite for electrochemical sensing of dopamine

Abstract Synthesis of hematite-thermally reduced graphite oxide (α-Fe2O3-TRGO) composite for the dopamine detection was carried out by a simple chemical method. The introduction of TRGO into α-Fe2O3 improved electrochemical properties, resulting from larger electroactive surface area of composite (0.016 cm2), more than twice increase than that of α-Fe2O3 (0.008 cm2), and higher conductivity as well. The electrocatalytic activity of α-Fe2O3-TRGO was investigated by the oxidation of dopamine in which a linear response of dopamine was obtained in the range of 0.1–5 mM with sensitivity of 0.02 mA/mM, limit of detection of 0.06 mM, and correlation coefficient of 0.99.

Intrauterine growth restriction increases impulsive behavior and is associated with altered dopamine transmission in both medial prefrontal and orbitofrontal cortex in female rats

Recent studies have implicated a role for impulsivity in the altered eating behaviors and the increased risk for obesity consistently associated with intrauterine growth restriction (IUGR). Changes in dopamine transmission within prefrontal areas are believed to contribute to these adverse outcomes. Here we investigated the impulsive behavior toward a delayed reward and evaluated dopamine levels and its receptors in the medial prefrontal (mPFC) and orbitofrontal (OFC) cortex of female adult rats exposed to IUGR. From day 10 of pregnancy and until birth, Sprague–Dawley dams received either an ad libitum (Adlib) or a 50% food-restricted (FR) diet. At birth, all pups were adopted by Adlib mothers, generating the groups Adlib/Adlib (control) and FR/Adlib (intrauterine growth-restricted). Adult impulsive behavior was evaluated using a Tolerance to Delay of Reward Task. In vivo dopamine responses to sweet food intake were measured by voltammetry, and D1, D2 and DAT levels were accessed by Western Blot. Animals from FR group showed a pronounced aversion to delayed rewards. DA response to sweet food was found to be blunted in the mPFC of FR animals, whereas in the OFC, the DA levels appear to be unaffected by reward consumption. Moreover, FR animals presented reduced D1 receptors in the OFC and a later increase in the mPFC D2 levels. These findings suggest that IUGR female rats are more impulsive and that the associated mechanism involves changes in the dopamine signaling in both the mPFC and OFC.

Influence of carbon nanostructure and oxygen moieties on dopamine adsorption and charge transfer kinetics at glassy carbon surfaces

Abnormal levels of the neurotransmitter dopamine have been linked to a variety of neurochemical disorders including depression and Parkinson's disease. Dopamine concentrations are often quantified electrochemically using biosensors prepared from carbon electrode materials such as carbon paste or glassy carbon. The charge transfer kinetics of dopamine is highly sensitive to carbon surface termination, including the presence of certain oxygen functional groups and adsorption sites. However, the nature of the binding sites and the effects of surface oxidation on the voltammetry of dopamine are both poorly understood. In this work the electrochemical response of dopamine at glassy carbon model surfaces was investigated to understand the effects of altering both the carbon nanostructure and oxygen surface chemistry on dopamine charge transfer kinetics and adsorption. Glassy carbon electrodes with low oxygen content and a high degree of surface graphitisation were prepared via thermal annealing at 900 °C, whilst highly oxidised glassy carbon electrodes were obtained through electrochemical anodisation at 1.8 V vs Ag/AgCl. The carbon surface structure and composition in each case was studied via X-Ray Photoelectron Spectroscopy. Voltammetry in solutions of dopamine at acidic pH confirmed that both annealing and anodisation treatments result in carbon surfaces with rapid charge transfer kinetics. However, dopamine adsorption occurs only at the low-oxygen, highly-graphitized carbon surface. Density functional theory studies on graphene model surfaces reveal that this behaviour is due to non-covalent interactions between the π-system of dopamine and the basal sites in the annealed surface. Simulations also show that the introduction of oxygen moieties disrupt these interactions and inhibit dopamine adsorption, in agreement with experiments. The results clarify the role of oxygen moieties and basal plane sites in facilitating both the adsorption of and charge transfer to DA at carbon electrodes.