Microdialysis provides a window on the brain. It permits measurements to be made of the extracellular concentration of chemicals whose primary role is an extracellular function, for example neurotransmitters. It has been widely adopted for investigations in animal models of disease and trauma and indeed in humans suffering trauma. The technique, as powerful as it is, has one major limitation - it cannot measure rapid changes that are relevant to phenomena such as spreading depolarization and behavior. There is a large gap in the time regime over which scientists can measure extracellular concentrations of the neurotransmitters dopamine (few nanomolar basal levels) and serotonin (sub-nanomolar basal levels) in the sub-minute to five minute range. A complementary technique, fast scan cyclic voltammetry measures changes in concentrations over the sub-second to several second timeframe. Based on our sound theoretical insight and technical improvements, we propose to improve the timescale of microdialysis to cover this important range. We will address three types of experiments with the new capability. (1) Are serotonin oscillations we have seen in preliminary work due to spreading depolarization? (2) What changes in the stress/anxiety-related neurotransmitter serotonin (5-hydroxytryptamine) are seen during the time an animal is making a decision in a stressful situation? (3) Can microdialysis be used to distinguish dopamine release upon an animal's receiving a reward from dopamine release upon the animal's receiving a cue associated with the reward?

Public Health Relevance

Reward-related behavior related to drug and alcohol abuse is governed at least in part by dopamine signal transmission. Serotonin is implicated in anxiety and depression. We will develop the capability to make meaningful observations on the dynamics of these transmitters on a timescale that is relevant to behavior. All of the improvements that we make can also be made by researcher's already practicing microdialysis. This work will empower many researchers to make more rapid and meaningful progress in understanding the chemical basis of behavior.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-ETTN-H (02))
Program Officer
Nadler, Laurie S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Schools of Arts and Sciences
United States
Zip Code
Gowers, S A N; Hamaoui, K; Cunnea, P et al. (2018) High temporal resolution delayed analysis of clinical microdialysate streams. Analyst 143:715-724
Ngo, Khanh T; Varner, Erika L; Michael, Adrian C et al. (2017) Monitoring Dopamine Responses to Potassium Ion and Nomifensine by in Vivo Microdialysis with Online Liquid Chromatography at One-Minute Resolution. ACS Chem Neurosci 8:329-338
Taylor, I Mitch; Du, Zhanhong; Bigelow, Emma T et al. (2017) Aptamer-functionalized neural recording electrodes for the direct measurement of cocaine in vivo. J Mater Chem B 5:2445-2458
Groskreutz, Stephen R; Weber, Stephen G (2016) Graphical Method for Choosing Optimized Conditions Given a Pump Pressure and a Particle Diameter in Liquid Chromatography. Anal Chem 88:11742-11749
Wilson, Rachael E; Groskreutz, Stephen R; Weber, Stephen G (2016) Improving the Sensitivity, Resolution, and Peak Capacity of Gradient Elution in Capillary Liquid Chromatography with Large-Volume Injections by Using Temperature-Assisted On-Column Solute Focusing. Anal Chem 88:5112-21
Groskreutz, Stephen R; Weber, Stephen G (2016) Temperature-assisted solute focusing with sequential trap/release zones in isocratic and gradient capillary liquid chromatography: Simulation and experiment. J Chromatogr A 1474:95-108
Gu, Hui; Varner, Erika L; Groskreutz, Stephen R et al. (2015) In Vivo Monitoring of Dopamine by Microdialysis with 1 min Temporal Resolution Using Online Capillary Liquid Chromatography with Electrochemical Detection. Anal Chem 87:6088-94
Groskreutz, Stephen R; Horner, Anthony R; Weber, Stephen G (2015) Temperature-based on-column solute focusing in capillary liquid chromatography reduces peak broadening from pre-column dispersion and volume overload when used alone or with solvent-based focusing. J Chromatogr A 1405:133-9
Groskreutz, Stephen R; Weber, Stephen G (2015) Quantitative evaluation of models for solvent-based, on-column focusing in liquid chromatography. J Chromatogr A 1409:116-24