Dopamine D1 receptors facilitate transmitter release

Nature. 1993 Nov 25;366(6453):344-7. doi: 10.1038/366344a0.


A physiological role for the dopamine D1 receptor has been difficult to define, particularly because of its complex pre- and postsynaptic localization in brain areas such as the striatum. In the midbrain, however, D1 receptors are selectively localized to the terminals of GABA (gamma-aminobutyric acid)-containing afferents. We have studied the actions of these D1 receptors on evoked GABA synaptic potentials recorded intracellularly from dopamine neurons in the ventral tegmental area (VTA). We report here that dopamine augmented GABAB inhibitory postsynaptic potentials ( in the presence of D2 receptor antagonists. This effect was mimicked by the D1 agonists SKF38393 and SKF82958 and blocked by the D1 antagonists SCH23390 and cis-flupenthixol. No modulation of the GABAA synaptic potential was observed. The postsynaptic actions of the GABAB agonist, baclofen, were unaffected by SKF38393, SCH23390 or cis-flupenthixol, confirming a presynaptic locus of D1 action. Additionally, D1 antagonists reduced the amplitude of the GABAB i.p.s.p. in the absence of D1 agonists. We conclude that dopamine acts tonically at presynaptic D1 receptors on the terminals of afferent GABA neurons to facilitate selectively GABAB-mediated neurotransmission in the midbrain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dopamine / pharmacology
  • Evoked Potentials / drug effects
  • Guinea Pigs
  • In Vitro Techniques
  • Neural Inhibition / drug effects
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / physiology*
  • Tegmentum Mesencephali / drug effects
  • Tegmentum Mesencephali / metabolism*
  • gamma-Aminobutyric Acid / metabolism*


  • Receptors, Dopamine D1
  • gamma-Aminobutyric Acid
  • Dopamine