Alterations in dopamine transmission occur during drug abuse and addiction. To understand these changes, it is necessary lo first understand the basic physiology 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 mentored training in electrophysiological and electrochemical techniques. The applicant has completed the K99 mentored phase of the award and has secured an independent tenure tract Assistant Professor position in the Department of Physiology and Biophysics at the Case Western Reserve University School (?f Medicine. Having completed 2 of the three aims of the original research proposal and having met his initial career goal of becoming an independent investigator studying the cellular and molecular basis of addiction, this current of the 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 proposal is to determine the relationship between extracellular dopamine and i(s physiological consequences. The objective during the mentored phase will be to determine the mechanisms regulating dopamine transmission. The hypothesis to be tested is that dopamine mediates transmission in the VTA in a tightly regulated, synaptic manner. The objective during the independent 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 of the basic mechanisms of dopamine transmission has hindered progress towards determining how transmission becomes dysregulated during the course of drug addiction. Thus this work has the potential to identify and direct new strategies to treat drug abuse and addiction.

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.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Sorensen, Roger
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Case Western Reserve University
Schools of Medicine
United States
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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