Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 293 (5539): 2465-2470

Copyright © 2001 by the American Association for the Advancement of Science

Dendrodendritic Inhibition Through Reversal of Dopamine Transport

Björn H. Falkenburger, Karen L. Barstow, Isabelle M. Mintz*

Synapses in the central nervous system are usually defined by presynaptic exocytotic release sites and postsynaptic differentiations. We report here a demonstration of dendrodendritic inhibition that does not engage a conventional synapse. Using amperometric and patch-clamp recordings in rat brain slices of the substantia nigra, we found that blockade of the dopamine transporter abolished the dendritic release of dopamine and the resulting self-inhibition. These findings demonstrate that dendrodendritic autoinhibition entails the carrier-mediated release of dopamine rather than conventional exocytosis. This suggests that some widely used antidepressants that inhibit the dopamine transporter may benefit patients in the early stages of Parkinson's disease.

Department of Pharmacology and Experimental Therapeutics, Boston University Medical Center, Boston, MA 02118, USA.
*   To whom correspondence should be addressed. E-mail: imintz{at}

Ca2+/Calmodulin-dependent Protein Kinase II{alpha} ({alpha}CaMKII) Controls the Activity of the Dopamine Transporter: IMPLICATIONS FOR ANGELMAN SYNDROME.
T. Steinkellner, J.-W. Yang, T. R. Montgomery, W.-Q. Chen, M.-T. Winkler, S. Sucic, G. Lubec, M. Freissmuth, Y. Elgersma, H. H. Sitte, et al. (2012)
J. Biol. Chem. 287, 29627-29635
   Abstract »    Full Text »    PDF »
Vesicular and Plasma Membrane Transporters for Neurotransmitters.
R. D. Blakely and R. H. Edwards (2012)
Cold Spring Harb Perspect Biol 4, a005595
   Abstract »    Full Text »    PDF »
Somatodendritic Dopamine Release Requires Synaptotagmin 4 and 7 and the Participation of Voltage-gated Calcium Channels.
J. A. Mendez, M.-J. Bourque, C. Fasano, C. Kortleven, and L.-E. Trudeau (2011)
J. Biol. Chem. 286, 23928-23937
   Abstract »    Full Text »    PDF »
An Ultra-Short Dopamine Pathway Regulates Basal Ganglia Output.
F.-W. Zhou, Y. Jin, S. G. Matta, M. Xu, and F.-M. Zhou (2009)
J. Neurosci. 29, 10424-10435
   Abstract »    Full Text »    PDF »
Dopamine Signaling Is Required for Depolarization-Induced Slow Current in Cerebellar Purkinje Cells.
Y. S. Kim, J. H. Shin, F. S. Hall, and D. J. Linden (2009)
J. Neurosci. 29, 8530-8538
   Abstract »    Full Text »    PDF »
Mobilization of Calcium from Intracellular Stores Facilitates Somatodendritic Dopamine Release.
J. C. Patel, P. Witkovsky, M. V. Avshalumov, and M. E. Rice (2009)
J. Neurosci. 29, 6568-6579
   Abstract »    Full Text »    PDF »
Synaptic Overflow of Dopamine in the Nucleus Accumbens Arises from Neuronal Activity in the Ventral Tegmental Area.
L. A. Sombers, M. Beyene, R. M. Carelli, and R. Mark Wightman (2009)
J. Neurosci. 29, 1735-1742
   Abstract »    Full Text »    PDF »
Drosophila Vesicular Monoamine Transporter Mutants Can Adapt to Reduced or Eliminated Vesicular Stores of Dopamine and Serotonin.
A. F. Simon, R. Daniels, R. Romero-Calderon, A. Grygoruk, H.-Y. Chang, R. Najibi, D. Shamouelian, E. Salazar, M. Solomon, L. C. Ackerson, et al. (2009)
Genetics 181, 525-541
   Abstract »    Full Text »    PDF »
Anomalous Dopamine Release Associated with a Human Dopamine Transporter Coding Variant.
M. S. Mazei-Robison, E. Bowton, M. Holy, M. Schmudermaier, M. Freissmuth, H. H. Sitte, A. Galli, and R. D. Blakely (2008)
J. Neurosci. 28, 7040-7046
   Abstract »    Full Text »    PDF »
Chemical transmission between dopaminergic neuron pairs.
M. Vandecasteele, J. Glowinski, J.-M. Deniau, and L. Venance (2008)
PNAS 105, 4904-4909
   Abstract »    Full Text »    PDF »
Dopamine Gates Action Potential Backpropagation in Midbrain Dopaminergic Neurons.
L. J. Gentet and S. R. Williams (2007)
J. Neurosci. 27, 1892-1901
   Abstract »    Full Text »    PDF »
Dopamine Transporter (DAT) Inhibitors Alleviate Specific Parkinsonian Deficits in Monkeys: Association with DAT Occupancy in Vivo.
B. K. Madras, M. A. Fahey, M. Goulet, Z. Lin, J. Bendor, C. Goodrich, P. C. Meltzer, D. R. Elmaleh, E. Livni, A. A. Bonab, et al. (2006)
J. Pharmacol. Exp. Ther. 319, 570-585
   Abstract »    Full Text »    PDF »
Heterogeneous Dopamine Neurochemistry in the Striatum: The Fountain-Drain Matrix.
M. Rodriguez, I. Morales, I. Gomez, S. Gonzalez, T. Gonzalez-Hernandez, and J. L. Gonzalez-Mora (2006)
J. Pharmacol. Exp. Ther. 319, 31-43
   Abstract »    Full Text »    PDF »
Control of the Subthalamic Innervation of Substantia Nigra Pars Reticulata by D1 and D2 Dopamine Receptors.
O. Ibanez-Sandoval, A. Hernandez, B. Floran, E. Galarraga, D. Tapia, R. Valdiosera, D. Erlij, J. Aceves, and J. Bargas (2006)
J Neurophysiol 95, 1800-1811
   Abstract »    Full Text »    PDF »
Psychoactive Substrates Stimulate Dopamine Transporter Phosphorylation and Down-regulation by Cocaine-sensitive and Protein Kinase C-dependent Mechanisms.
M. A. Cervinski, J. D. Foster, and R. A. Vaughan (2005)
J. Biol. Chem. 280, 40442-40449
   Abstract »    Full Text »    PDF »
Regulation of Drug Reward by cAMP Response Element-Binding Protein: Evidence for Two Functionally Distinct Subregions of the Ventral Tegmental Area.
V. G. Olson, C. P. Zabetian, C. A. Bolanos, S. Edwards, M. Barrot, A. J. Eisch, T. Hughes, D. W. Self, R. L. Neve, and E. J. Nestler (2005)
J. Neurosci. 25, 5553-5562
   Abstract »    Full Text »    PDF »
Folding Efficiency Is Rate-limiting in Dopamine D4 Receptor Biogenesis.
K. Van Craenenbroeck, S. D. Clark, M. J. Cox, J. N. Oak, F. Liu, and H. H. M. Van Tol (2005)
J. Biol. Chem. 280, 19350-19357
   Abstract »    Full Text »    PDF »
Amphetamine induces dopamine efflux through a dopamine transporter channel.
K. M. Kahlig, F. Binda, H. Khoshbouei, R. D. Blakely, D. G. McMahon, J. A. Javitch, and A. Galli (2005)
PNAS 102, 3495-3500
   Abstract »    Full Text »    PDF »
Zinc Potentiates an Uncoupled Anion Conductance Associated with the Dopamine Transporter.
A.-K. Meinild, H. H. Sitte, and U. Gether (2004)
J. Biol. Chem. 279, 49671-49679
   Abstract »    Full Text »    PDF »
From The Cover: Firing properties of dopamine neurons in freely moving dopamine-deficient mice: Effects of dopamine receptor activation and anesthesia.
S. Robinson, D. M. Smith, S. J. Y. Mizumori, and R. D. Palmiter (2004)
PNAS 101, 13329-13334
   Abstract »    Full Text »    PDF »
Aspartate 345 of the Dopamine Transporter Is Critical for Conformational Changes in Substrate Translocation and Cocaine Binding.
N. Chen, J. Rickey, J. L. Berfield, and M. E. A. Reith (2004)
J. Biol. Chem. 279, 5508-5519
   Abstract »    Full Text »    PDF »
Dopamine modulates the plasticity of mechanosensory responses in Caenorhabditis elegans.
S. Sanyal, R. F. Wintle, K. S. Kindt, W. M. Nuttley, R. Arvan, P. Fitzmaurice, E. Bigras, D. C. Merz, T. E. Hebert, D. van der Kooy, et al. (2004)
EMBO J. 23, 473-482
   Abstract »    Full Text »    PDF »
Dendritic Projections and Dye-Coupling in Dopaminergic Neurons of the Substantia Nigra Examined in Horizontal Brain Slices From Young Rats.
J. Y. Lin, M. van Wyk, T. K. Bowala, M.-Y. Teo, and J. Lipski (2003)
J Neurophysiol 90, 2531-2535
   Abstract »    Full Text »    PDF »
Dynamic Equilibrium of Neurotransmitter Transporters: Not Just for Reuptake Anymore.
G. B. Richerson and Y. Wu (2003)
J Neurophysiol 90, 1363-1374
   Abstract »    Full Text »    PDF »
Immunohistochemical Changes in the Mouse Striatum Induced by the Pyrethroid Insecticide Permethrin.
J. T. Pittman, C. A. Dodd, and B. G. Klein (2003)
International Journal of Toxicology 22, 359-370
   Abstract »    PDF »
The Dopamine Transporter Constitutively Internalizes and Recycles in a Protein Kinase C-regulated Manner in Stably Transfected PC12 Cell Lines.
M. K. Loder and H. E. Melikian (2003)
J. Biol. Chem. 278, 22168-22174
   Abstract »    Full Text »    PDF »
H. Khoshbouei, H. Wang, J. D. Lechleiter, J. A. Javitch, and A. Galli (2003)
J. Biol. Chem. 278, 12070-12077
   Abstract »    Full Text »    PDF »
Somatodendritic Secretion in Oxytocin Neurons Is Upregulated during the Female Reproductive Cycle.
C. P. J. de Kock, K. D. B. Wierda, L. W. J. Bosman, R. Min, J.-J. Koksma, H. D. Mansvelder, M. Verhage, and A. B. Brussaard (2003)
J. Neurosci. 23, 2726-2734
   Abstract »    Full Text »    PDF »
Enhanced Responsiveness to Novelty and Cocaine Is Associated with Decreased Basal Dopamine Uptake and Release in the Nucleus Accumbens: Quantitative Microdialysis in Rats under Transient Conditions.
V. I. Chefer, I. Zakharova, and T. S. Shippenberg (2003)
J. Neurosci. 23, 3076-3084
   Abstract »    Full Text »    PDF »
Muscarinic and Nicotinic Cholinergic Mechanisms in the Mesostriatal Dopamine Systems.
F.-M. Zhou, C. Wilson, and J. A. Dani (2003)
Neuroscientist 9, 23-36
   Abstract »    PDF »
Transport-Mediated Synapses in the Retina.
E. A. Schwartz (2002)
Physiol Rev 82, 875-891
   Abstract »    Full Text »    PDF »
Methylphenidate Redistributes Vesicular Monoamine Transporter-2: Role of Dopamine Receptors.
V. Sandoval, E. L. Riddle, G. R. Hanson, and A. E. Fleckenstein (2002)
J. Neurosci. 22, 8705-8710
   Abstract »    Full Text »    PDF »
Acute Cocaine Differentially Alters Accumbens and Striatal Dopamine Clearance in Low and High Cocaine Locomotor Responders: Behavioral and Electrochemical Recordings in Freely Moving Rats.
J. Sabeti, G. A. Gerhardt, and N. R. Zahniser (2002)
J. Pharmacol. Exp. Ther. 302, 1201-1211
   Abstract »    Full Text »    PDF »
The Role of Zinc Ions in Reverse Transport Mediated by Monoamine Transporters.
P. Scholze, L. Norregaard, E. A. Singer, M. Freissmuth, U. Gether, and H. H. Sitte (2002)
J. Biol. Chem. 277, 21505-21513
   Abstract »    Full Text »    PDF »
Neurobiology of Birth Weight Influence on Blood Pressure Values and Variability in Children and Adolescents * Response.
E. H. Friedman and E. Lurbe (2002)
Hypertension 39, e15
   Full Text »    PDF »
NEUROBIOLOGY: Dopamine's Reversal of Fortune.
R. D. Blakely (2001)
Science 293, 2407-2409
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882