The proposed Core will continue to provide the biophysical-technical infrastructures and intellectual support required to test the novel hypotheses of this proposal that are relevant to the structure-function and functional regulation of the dopamine (DA) transporter (DAT). DAT is the major molecular target responsible for the rewarding properties and abuse potential of amphetamine (AMPH), cocaine, and related psychostimulants. AMPH, as a result of its ability to reverse the inward transport of DA, is believed to induce DA efflux and therefore to increase extracellular DA levels. Thus, the long-term goals of the Core research team are to enable the PPG Consortium of Investigators (COI) to determine the cellular/structural bases of substrate efflux induced by AMPH. The Core will continue to be a resource and to develop state of the art technologies to address key experimental approaches in a unified and coordinated manner for the investigators of the PPG. The Core will ensure access to advanced technologies focused on the mechanisms of DATs in a manner that allows for comparisons among laboratories and between systems. The Core will also support and unify collaborative efforts among the members of the COI to facilitate them to address complex experiments and together overcome experimental difficulties throughout the PPG. These activities of the Core will continue to foster synergy between the different research groups of this project. Finally, the Core is devoted to increasing the availability of new approaches to strengthen the ability of the COI to answer both ongoing collaborative efforts as well as new scientific directions.
Stimulant abuse and potentially other dopamine (DA)-related pathologies such as schizophrenia, are a tremendous public health burden. The DA transporter (DAT), which regulates extracellular brain DA, Is the major molecular target of several psychoactive drugs. Including amphetamine (AMPH). This proposal will analyze how AMPH by altering DAT function disrupts DA homeostasis possibly leading to addiction.
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