Loss of autoreceptor functions in mice lacking the dopamine transporter.
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.
Howard Hughes Medical Institute, Department of Cell Biology, North Carolina, USA.
S R
SR
Jones
R R
RR
Gainetdinov
X T
XT
Hu
D C
DC
Cooper
R M
RM
Wightman
F J
FJ
White
M G
MG
Caron
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D004558:Electric Stimulation; D005246:Feedback / Q000502:physiology*; D017353:Gene Deletion; D006719:Homovanillic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000493:pharmacokinetics
D002352:Carrier Proteins; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C493215:Slc6a3 protein, mouse; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D004298:Dopamine; D006719:Homovanillic Acid; C064246:NCQ 298