The time course of dopamine transmission in the ventral tegmental area

J Neurosci. 2009 Oct 21;29(42):13344-52. doi: 10.1523/JNEUROSCI.3546-09.2009.

Abstract

Synaptic transmission mediated by G-protein coupled receptors (GPCR) is not generally thought to be point-to-point. To determine the extent over which dopamine signals in the midbrain, the present study examined the concentration and time course of dopamine that underlies a D(2)-receptor IPSC (D(2)-IPSC) in the ventral tegmental area. Extracellular dopamine was measured electrochemically while simultaneously recording D(2)-IPSCs. The presence of dopamine was brief relative to the IPSC, suggesting that G-protein dependent potassium channel activation determined the IPSC time course. The activation kinetics of D(2) receptor-dependent potassium current was studied using outside-out patch recordings with rapid application of dopamine. Dopamine applied at a minimum concentration of 10 mum for a maximum of 100 ms mimicked the IPSC. Higher concentrations applied for as little as 5 ms did not change the kinetics of the current. The results indicate that both the intrinsic kinetics of G-protein coupled receptor signaling and a rapidly rising high concentration of dopamine determine the time course of the IPSC. Thus, dopamine transmission in the midbrain is more localized then previously proposed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysics
  • Chelating Agents / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Dopamine / metabolism*
  • Dopamine / pharmacology
  • Dopamine Agonists / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Stimulation / methods
  • Electrochemistry / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / physiology
  • GABA Antagonists / pharmacology
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology*
  • Male
  • Mice
  • Mice, Inbred DBA
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods
  • Phosphinic Acids / pharmacology
  • Picrotoxin / pharmacology
  • Propanolamines / pharmacology
  • Quinoxalines / pharmacology
  • Quinpirole / pharmacology
  • Rhodamines / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Statistics, Nonparametric
  • Temperature
  • Time Factors
  • Ventral Tegmental Area / cytology*
  • Ventral Tegmental Area / physiology*

Substances

  • Chelating Agents
  • Dopamine Agonists
  • Excitatory Amino Acid Antagonists
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GABA Antagonists
  • Phosphinic Acids
  • Propanolamines
  • Quinoxalines
  • Rhodamines
  • Picrotoxin
  • CGP 55845A
  • Quinpirole
  • Egtazic Acid
  • FG 9041
  • Dizocilpine Maleate
  • sulforhodamine 101
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Dopamine