DOPAMINE D1 RECEPTORS FACILITATE TRANSMITTER RELEASE

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 striatum1. In the midbrain, however, D1 receptors are selectively localized to the terminals of GABA (gamma-aminobutyric acid)-containing afferents2-4. 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 GABA(B) inhibitory postsynaptic potentials (i.p.s.ps) 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 GABA(A) synaptic potential was observed. The postsynaptic actions of the GABA(B) 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 GABA(B) 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 GABA(B)-mediated neurotransmission in the midbrain.