Loss of autoreceptor functions in mice lacking the dopamine transporter
Sara R. Jones1, Raul R. Gainetdinov1, Xiu-Ti Hu2, Donald C. Cooper2, R. Mark Wightman3, Francis J. White2
& Marc G. Caron1
1
Howard Hughes Medical Institute, Departments of Cell
Biology and Medicine, Box 3287, 487 CARL Bldg.,
Duke University Medical Center, Durham, North Carolina
27710, USA
2
Finch University of Health Sciences, The Chicago Medical
School, 3333 Green Bay Road, North Chicago,
Illinois 60064-3095, USA
3
Department of Chemistry and Curriculum in Neurobiology,
CB #3290 Venable Hall University of North Carolina
at Chapel Hill, Chapel Hill, North Carolina
27599-3290, USA
Autoreceptors provide an important inhibitory feedback mechanism for dopamine
neurons by altering neuronal functions in response to changes in extracellular
levels of dopamine. Elevated dopamine may be a component of several neuropsychiatric
disorders. However, evidence concerning the state of autoreceptors in such
conditions has remained elusive. The function of dopamine autoreceptors was
assessed in mice lacking the dopamine transporter (DAT). Genetic deletion
of the DAT gene in mice results in a persistent elevation in levels of extracellular
dopamine. Direct assessment of impulse-, synthesis- and release-regulating
autoreceptors in these mice reveals a nearly complete loss of function. These
findings may provide insight into the neurochemical consequences of hyperdopaminergia.
