Dendrodendritic inhibition through reversal of dopamine transport.
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.
Falkenburger
B H
BH
Department of Pharmacology and Experimental Therapeutics, Boston University Medical Center, Boston, MA 02118, USA.
Barstow
K L
KL
Mintz
I M
IM
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials; D005089:Exocytosis; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins; D008564:Membrane Potentials; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000502:physiology
D002352:Carrier Proteins; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D017448:Receptors, Dopamine D2; D018698:Glutamic Acid; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D012964:Sodium; D002118:Calcium; D004298:Dopamine