Dopamine D1 receptors facilitate transmitter release

Donald L. Cameron, John T. Williams

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Abstract

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 (γ-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 GABAB 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 GABAA synaptic potential was observed. The postsynaptic actions of the GABA Bagonist, 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.

Original languageEnglish (US)
Pages (from-to)344-347
Number of pages4
JournalNature
Volume366
Issue number6453
DOIs
StatePublished - Jan 1 1993

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