Content area
Full Text
About the Authors:
Xiaowei Zhang
Affiliation: Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California, United States of America
Elaine L. Bearer
Affiliations Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California, United States of America, Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States of America
Benoit Boulat
Affiliation: Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California, United States of America
F. Scott Hall
Affiliation: Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, United States of America
George R. Uhl
Affiliation: Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, United States of America
Russell E. Jacobs
* E-mail: [email protected]
Affiliation: Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California, United States of America
Introduction
The dopamine transporter (DAT, SLC6A3) acts to terminate dopaminergic neurotransmission through reuptake of dopamine from the synaptic cleft into presynaptic neurons. Dopamine is a key neurotransmitter that can influence cognition, emotion, and movement; and many drugs exert their psychotropic effects via DAT [1], [2], [3], [4], [5]. In particular, dopamine plays an important role in the development and maintenance of addiction [6], [7] where much study has been devoted to its role in reward circuitry associated with the mesolimbic and mesocortical pathways [8], [9], [10], [11]. Dopaminergic neurons originate in the ventral tegmental area (VTA) and substantia nigra compacta (SNc), and projections to areas including the prefrontal cortex [12], integrate reward circuitry with executive functions mediated by the frontal cortex. The mesocortical and mesolimbic projections are part of the brain “reward circuit,” and are direct targets of psychostimulant drugs of abuse. This circuitry is also implicated in mental illnesses that include schizophrenia, major depressive disorder, and attention-deficit hyperactivity disorder [13], [14], [15]. Interactions among these, and other, structures are complex, with numerous opportunities for feedback involving a variety of connections and neuronal types (GABAergic, glutamatergic, dopaminergic, serotonergic, cholinergic, etc.) [16], [17], [18]. Mouse models with specific genetic modifications in the components of these pathways allow us to probe the ramifications of well-defined alterations with an eye toward parsing endophenotypes of pathological conditions and behaviors. Studies of mice with genetic manipulations of DAT [5], [19], [20],...