@article{forderhase_styers_lee_sombers_2020, title={Simultaneous voltammetric detection of glucose and lactate fluctuations in rat striatum evoked by electrical stimulation of the midbrain}, volume={412}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-020-02797-0}, abstractNote={Glucose and lactate provide energy for cellular function in the brain and serve as an important carbon source in the synthesis of a variety of biomolecules. Thus, there is a critical need to quantitatively monitor these molecules in situ on a time scale commensurate with neuronal function. In this work, carbon-fiber microbiosensors were coupled with fast-scan cyclic voltammetry to monitor glucose and lactate fluctuations at a discrete site within rat striatum upon electrical stimulation of the midbrain projection to the region. Systematic variation of stimulation parameters revealed the distinct dynamics by which glucose and lactate responded to the metabolic demand of synaptic function. Immediately upon stimulation, extracellular glucose and lactate availability rapidly increased. If stimulation was sufficiently intense, concentrations then immediately fell below baseline in response to incurred metabolic demand. The dynamics were dependent on stimulation frequency, such that more robust fluctuations were observed when the same number of pulses was delivered at a higher frequency. The rates at which glucose was supplied to, and depleted from, the local recording region were dependent on stimulation intensity, and glucose dynamics led those of lactate in response to the most substantial stimulations. Glucose fluctuated over a larger concentration range than lactate as stimulation duration increased, and glucose fell further from baseline concentrations. These real-time measurements provide an unprecedented direct comparison of glucose and lactate dynamics in response to metabolic demand elicited by neuronal activation.}, number={24}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Forderhase, Alexandra G. and Styers, Hannah C. and Lee, Christie A. and Sombers, Leslie A.}, year={2020}, month={Sep}, pages={6611–6624} }
 @article{smith_gosrani_lee_mccarty_sombers_2018, title={Carbon-Fiber Microbiosensor for Monitoring Rapid Lactate Fluctuations in Brain Tissue Using Fast-Scan Cyclic Voltammetry}, volume={90}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/acs.analchem.8b03694}, DOI={10.1021/acs.analchem.8b03694}, abstractNote={Recent studies have described a role for lactate in brain energy metabolism and energy formation, challenging the conventional view that glucose is the principle energy source for brain function. To date, lactate dynamics in the brain are largely unknown, limiting insight into function. We addressed this by developing and characterizing a lactate oxidase-modified carbon-fiber microelectrode coupled with fast-scan cyclic voltammetry. This new tool boasts a sensitivity for lactate of 22 ± 1 nA·mM-1 and LOD of 7.0 ± 0.7 μM. The approach has enabled detection of rapid lactate fluctuations with unprecedented spatiotemporal resolution as well as excellent stability, selectivity, and sensitivity. The technology was characterized both in vitro and in vivo at discrete recording sites in rat striatum. We provide evidence that striatal lactate availability increases biphasically in response to electrical stimulation of the dopaminergic midbrain in the anesthetized rat. This new tool for real-time detection of lactate dynamics promises to improve understanding of how lactate availability underscores neuronal function and dysfunction.}, number={21}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Smith, Samantha K. and Gosrani, Saahj P. and Lee, Christie A. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2018}, month={Oct}, pages={12994–12999} }
 @article{calhoun_meunier_lee_mccarty_sombers_2018, title={Characterization of a Multiple-Scan-Rate Voltammetric Waveform for Real-Time Detection of Met-Enkephalin}, volume={10}, ISSN={1948-7193 1948-7193}, url={http://dx.doi.org/10.1021/acschemneuro.8b00351}, DOI={10.1021/acschemneuro.8b00351}, abstractNote={Opioid peptides are critically involved in a variety of physiological functions necessary for adaptation and survival, and as such, understanding the precise actions of endogenous opioid peptides will aid in identification of potential therapeutic strategies to treat a variety of disorders. However, few analytical tools are currently available that offer both the sensitivity and spatial resolution required to monitor peptidergic concentration fluctuations in situ on a time scale commensurate with that of neuronal communication. Our group has developed a multiple-scan-rate waveform to enable real-time voltammetric detection of tyrosine containing neuropeptides. Herein, we have evaluated the waveform parameters to increase sensitivity to methionine-enkephalin (M-ENK), an endogenous opioid neuropeptide implicated in pain, stress, and reward circuits. M-ENK dynamics were monitored in adrenal gland tissue, as well as in the dorsal striatum of anesthetized and freely behaving animals. The data reveal cofluctuations of catecholamine and M-ENK in both locations and provide measurements of M-ENK dynamics in the brain with subsecond temporal resolution. Importantly, this work also demonstrates how voltammetric waveforms can be customized to enhance detection of specific target analytes, broadly speaking.}, number={4}, journal={ACS Chemical Neuroscience}, publisher={American Chemical Society (ACS)}, author={Calhoun, S. E. and Meunier, C. J. and Lee, C. A. and McCarty, G. S. and Sombers, L. A.}, year={2018}, month={Dec}, pages={2022–2032} }
 @article{smith_lee_dausch_horman_patisaul_mccarty_sombers_2017, title={Simultaneous Voltammetric Measurements of Glucose and Dopamine Demonstrate the Coupling of Glucose Availability with Increased Metabolic Demand in the Rat Striatum}, volume={8}, ISSN={1948-7193 1948-7193}, url={http://dx.doi.org/10.1021/acschemneuro.6b00363}, DOI={10.1021/acschemneuro.6b00363}, abstractNote={Cerebral blood flow ensures delivery of nutrients, such as glucose, to brain sites with increased metabolic demand. However, little is known about rapid glucose dynamics at discrete locations during neuronal activation in vivo. Acute exposure to many substances of abuse elicits dopamine release and neuronal activation in the striatum; however, the concomitant changes in striatal glucose remain largely unknown. Recent developments have combined fast-scan cyclic voltammetry with glucose oxidase enzyme modified carbon-fiber microelectrodes to enable the measurement of glucose dynamics with subsecond temporal resolution in the mammalian brain. This work evaluates several waveforms to enable the first simultaneous detection of endogenous glucose and dopamine at single recording sites. These molecules, one electroactive and one nonelectroactive, were found to fluctuate in the dorsal striatum in response to electrical stimulation of the midbrain and systemic infusion of cocaine/raclopride. The data reveal the second-by-second dynamics of these species in a striatal microenvironment, and directly demonstrate the coupling of glucose availability with increased metabolic demand. This work provides a foundation that will enable detailed investigation of local mechanisms that regulate the coupling of cerebral blood flow with metabolic demand under normal conditions, and in animal studies of drug abuse and addiction.}, number={2}, journal={ACS Chemical Neuroscience}, publisher={American Chemical Society (ACS)}, author={Smith, Samantha K. and Lee, Christie A. and Dausch, Matthew E. and Horman, Brian M. and Patisaul, Heather B. and McCarty, Gregory S. and Sombers, Leslie A.}, year={2017}, month={Jan}, pages={272–280} }
 @article{qi_thomas_white_smith_lee_wilson_sombers_2016, title={Unmasking the Effects of L-DOPA on Rapid Dopamine Signaling with an Improved Approach for Nafion Coating Carbon-Fiber Microelectrodes}, volume={88}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.6b01871}, abstractNote={L-DOPA has been the gold standard for symptomatic treatment of Parkinson's disease. However, its efficacy wanes over time as motor complications develop. Very little is known about how L-DOPA therapy affects the dynamics of fluctuating dopamine concentrations in the striatum on a rapid time scale (seconds). Electrochemical studies investigating the effects of L-DOPA treatment on electrically evoked dopamine release have reported conflicting results with significant variability. We hypothesize that the uncertainty in the electrochemical data is largely due to electrode fouling caused by polymerization of L-DOPA and endogenous catecholamines on the electrode surface. Thus, we have systematically optimized the procedure for fabricating cylindrical, Nafion-coated, carbon-fiber microelectrodes. This has enabled rapid and reliable detection of L-DOPA's effects on striatal dopamine signaling in intact rat brain using fast-scan cyclic voltammetry. An acute dose of 5 mg/kg L-DOPA had no significant effect on dopamine dynamics, demonstrating the highly efficient regulatory mechanisms at work in the intact brain. In contrast, administration of 200 mg/kg L-DOPA significantly increased the amplitude of evoked dopamine release by ∼200%. Overall, this work describes a reliable tool that allows a better measure of L-DOPA augmented dopamine release in vivo, measured using fast-scan cyclic voltammetry. It provides a methodology that improves the stability and performance of the carbon-fiber microelectrode when studying the molecular mechanisms underlying L-DOPA therapy and also promises to benefit a wide variety of studies because Nafion is so commonly used in electroanalytical chemistry.}, number={16}, journal={ANALYTICAL CHEMISTRY}, author={Qi, Lingjiao and Thomas, Elina and White, Stephanie H. and Smith, Samantha K. and Lee, Christie A. and Wilson, Leslie R. and Sombers, Leslie A.}, year={2016}, month={Aug}, pages={8129–8136} }
 @article{randall_lee_podurgiel_hart_yohn_jones_rowland_lopez-cruz_correa_salamone_2015, title={Bupropion Increases Selection of High Effort Activity in Rats Tested on a Progressive Ratio/Chow Feeding Choice Procedure: Implications for Treatment of Effort-Related Motivational Symptoms}, volume={18}, ISSN={["1469-5111"]}, DOI={10.1093/ijnp/pyu017}, abstractNote={Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans.}, number={2}, journal={INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY}, author={Randall, Patrick A. and Lee, Christie A. and Podurgiel, Samantha J. and Hart, Evan and Yohn, Samantha E. and Jones, Myles and Rowland, Margaret and Lopez-Cruz, Laura and Correa, Merce and Salamone, John D.}, year={2015}, month={Jan} }
 @article{yohn_thompson_randall_lee_muller_baqi_correa_salamone_2015, title={The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A(2A) antagonist MSX-3 and the catecholamine uptake blocker bupropion}, volume={232}, ISSN={["1432-2072"]}, DOI={10.1007/s00213-014-3766-0}, abstractNote={[[{:Label=>"RATIONALE", :NlmCategory=>"BACKGROUND"}, "Depressed people show effort-related motivational symptoms, such as anergia, retardation, lassitude, and fatigue. Animal tests can model these motivational symptoms, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, at low doses, preferentially depletes dopamine."], [{:Label=>"OBJECTIVES", :NlmCategory=>"OBJECTIVE"}, "The current studies investigated the effects of tetrabenazine on effort-based decision making using the T-maze barrier task."], [{:Label=>"METHODS", :NlmCategory=>"METHODS"}, "Rats were tested in a T-maze in which the choice arms of the maze contain different reinforcement densities, and under some conditions, a vertical barrier was placed in the high-density arm to provide an effort-related challenge. The first experiment assessed the effects of tetrabenazine under different maze conditions: a barrier in the arm with 4 food pellets and 2 pellets in the no barrier arm (4-2 barrier), 4 pellets in one arm and 2 pellets in the other with no barrier in either arm (no barrier), and 4 pellets in the barrier arm with no pellets in the other (4-0 barrier)."], [{:Label=>"RESULTS", :NlmCategory=>"RESULTS"}, "Tetrabenazine (0.25-0.75 mg/kg IP) decreased selection of the high cost/high reward arm when the barrier was present, but had no effect on choice under the no barrier and 4-0 barrier conditions. The effects of tetrabenazine on barrier climbing in the 4-2 condition were reversed by the adenosine A2A antagonist MSX-3 and the catecholamine uptake inhibitor and antidepressant bupropion."], [{:Label=>"CONCLUSIONS", :NlmCategory=>"CONCLUSIONS"}, "These studies have implications for the development of animal models of the motivational symptoms of depression and other disorders."]]}, number={7}, journal={PSYCHOPHARMACOLOGY}, author={Yohn, Samantha E. and Thompson, Christian and Randall, Patrick A. and Lee, Christie A. and Muller, Christa E. and Baqi, Younis and Correa, Merce and Salamone, John D.}, year={2015}, month={Apr}, pages={1313–1323} }