Aliera!ions in dopamine iransmission occur during drug abuse and addiction. To undcrstatid these changes, it is necessary lo first understand Ilie basic physicilugy that underlies dopamine transmission.
The aim of this Pathway to Independence Award (K9WR(K)) proposal is to investigate the mechanisms of dopamine transmission while providing the candidate (Dr Christopher Ford) with the necessary nsentored training in electrophysiological and electrochemical techniques. The applicant has completed the K99 mentored phase ofthe award and has secured an indcfJcndent tenure Iract Assistant Professor jxisition in the Departmenl of Physiology and Biophysics at the Case Western Reserve University School ( f Medicine. Having completed 2 of the three aims ofthe origninal research pro(X)sal and having met his initial career goal of becoming an independent investigator studying the cellular and molecular basis of addiction, this current pha.se ofthe proposal (R(X)) is designed to provide independent support that will I K used to further his studies, complete the remaining aims of the award and gain long-lemi ROI grant support. The central aim of this pro|M: sal is to dclcnnine the relationship between extracellular dopamine and i(s physiological consequences. The objective during die mentored pha.se will be to deiermine the mechanisms regulating dopamine transmission. The hypothesis to be le.sted is that dopamine mediates iransmission in the VTA in a tightly regulated, synaptic manner. The objeclive during the inde|>endent phase will be to define the concentration and duration of dopamine mediating transmission. The hypothesis being that transient, high concentrations of dopamine mediate transmission. A lack of knowledge ofthe basic mechanisms of dopamine transmission has hindered progre.s.s towards determining how transmission becomes dysregulated during [he course of drug addiction. Thus this work lias Ihe {xueniial to ideniiy and direct new strategies to treat tirug abuse and atldiction.

Public Health Relevance

(Soo irvjlruclions); Determining the mechanisms by which dopamine mediates transmission is a key first step to providing the framework necessary for understanding how this system is altered as a result ol chronic drug use. A bettor understanding of the events linking dopamine release to its physiological actions v/ill be significant as it has the potential to direct new strategies for the treatment of drug abuse and addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Transition Award (R00)
Project #
4R00DA026417-03
Application #
8207551
Study Section
Special Emphasis Panel (NSS)
Program Officer
Sorensen, Roger
Project Start
2011-04-01
Project End
2014-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
3
Fiscal Year
2011
Total Cost
$249,000
Indirect Cost
Name
Case Western Reserve University
Department
Physiology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Ford, C P (2014) The role of D2-autoreceptors in regulating dopamine neuron activity and transmission. Neuroscience 282:13-22
Courtney, Nicholas A; Ford, Christopher P (2014) The timing of dopamine- and noradrenaline-mediated transmission reflects underlying differences in the extent of spillover and pooling. J Neurosci 34:7645-56
Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P (2014) Phasic dopamine release drives rapid activation of striatal D2-receptors. Neuron 84:164-176
Courtney, Nicholas A; Mamaligas, Aphroditi A; Ford, Christopher P (2012) Species differences in somatodendritic dopamine transmission determine D2-autoreceptor-mediated inhibition of ventral tegmental area neuron firing. J Neurosci 32:13520-8
Gantz, Stephanie C; Ford, Christopher P; Neve, Kim A et al. (2011) Loss of Mecp2 in substantia nigra dopamine neurons compromises the nigrostriatal pathway. J Neurosci 31:12629-37
Ford, Christopher P; Gantz, Stephanie C; Phillips, Paul E M et al. (2010) Control of extracellular dopamine at dendrite and axon terminals. J Neurosci 30:6975-83
Ford, Christopher P; Phillips, Paul E M; Williams, John T (2009) The time course of dopamine transmission in the ventral tegmental area. J Neurosci 29:13344-52