Dopamine inhibits GABA(A) currents in ventral tegmental area dopamine neurons via activation of presynaptic G-protein coupled inwardly-rectifying potassium channels

Neuroscience. 2010 Feb 17;165(4):1159-69. doi: 10.1016/j.neuroscience.2009.11.045. Epub 2009 Nov 26.


Dopamine (DA) neurons in the ventral tegmental area (VTA) constitute the origin of major dopaminergic neural pathways associated with essential functions including reward, motivation and cognition. Hence, regulation of VTA DA neurons' excitability is of important significance. Like other neurons, the activity level of VTA DA neurons is considerably determined by excitatory and inhibitory synaptic inputs. Here we show that DA itself, the most available modulator in the VTA, causes an inhibition of GABA receptor type A (GABA(A)R)-mediated evoked-IPSC (eIPSC) recorded from rat VTA DA neurons. The DA-induced inhibition was accomplished by activation of DA receptors, known to inhibit adenylyl cyclase activity (D2-like receptors), and was absent when these receptors were blocked. Moreover, blocking of either GABA receptor type B (GABA(B)R) or G-protein coupled inwardly-rectifying potassium (GIRK) channels was also found to effectively prevent the DA-induced inhibition of GABA(A)R eIPSC. In addition, we found that DA changes the values of both paired-pulse ratio (PPR) and coefficient of variation (CV) of GABA(A)R eIPSC amplitude, similar to the changes obtained by lowering the extracellular calcium concentration. Taken together, we propose that activation of D2-like receptors and GABA(B)R in the VTA enhances presynaptic GIRK channels activity, which in turn leads to reduced GABA release. The consequence of reduced GABA release on VTA DA neurons may contribute to their increased activity. Accordingly, a novel potential regulatory form of VTA DA neurons' excitability, which involves presynaptic potassium channels, is proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Dopamine / metabolism*
  • Evoked Potentials / physiology
  • Extracellular Space / metabolism
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism*
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / physiology
  • Male
  • Neural Inhibition / physiology
  • Neurons / physiology*
  • Presynaptic Terminals / physiology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine D2 / metabolism
  • Receptors, GABA-A / metabolism*
  • Receptors, GABA-B / metabolism
  • Synaptic Transmission / physiology
  • Ventral Tegmental Area / physiology*
  • gamma-Aminobutyric Acid / metabolism


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Receptors, Dopamine D2
  • Receptors, GABA-A
  • Receptors, GABA-B
  • gamma-Aminobutyric Acid
  • Calcium
  • Dopamine