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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH104386-01
Application #
8750990
Study Section
Special Emphasis Panel (ZRG1-ETTN-H (02))
Program Officer
Nadler, Laurie S
Project Start
2014-08-15
Project End
2018-06-30
Budget Start
2014-08-15
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$296,899
Indirect Cost
$71,899
Name
University of Pittsburgh
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213