Abstract
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.
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Acknowledgements
We thank Jason Holt and Susan Suter for technical assistance. S.R.J. is the recipient of a Young Investigator Award from NARSAD. This work was supported in part by NIH grant NS 19576, an unrestricted Neuroscience Award from Bristol-Myers Squibb and an unrestricted grant from Zeneca Pharmaceuticals to M.G.C. M.G.C. is an Investigator of the Howard Hughes Medical Institute. R.R.G. is a visiting scientist from the Institute of Pharmacology RAMS, Moscow, Russia.
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Jones, S., Gainetdinov, R., Hu, XT. et al. Loss of autoreceptor functions in mice lacking the dopamine transporter . Nat Neurosci 2, 649–655 (1999). https://doi.org/10.1038/10204
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DOI: https://doi.org/10.1038/10204
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