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Dopamine D1 receptors facilitate transmitter release
1Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
Nature
|November 25, 1993
Summary
Dopamine D1 receptors tonically facilitate GABA B neurotransmission in the midbrain. These presynaptic receptors on GABA afferents enhance inhibitory postsynaptic potentials in dopamine neurons.
Area of Science:
- Neuroscience
- Neuropharmacology
Background:
- The physiological role of dopamine D1 receptors is complex due to their pre- and postsynaptic localization.
- D1 receptors in the midbrain are specifically found on the terminals of GABA-containing afferents.
Purpose of the Study:
- To investigate the presynaptic actions of dopamine D1 receptors on GABAergic neurotransmission in the ventral tegmental area (VTA).
Main Methods:
- Intracellular recordings of evoked GABA synaptic potentials in VTA dopamine neurons.
- Pharmacological manipulation using D1 and D2 receptor agonists and antagonists.
- Assessment of GABAA and GABAB inhibitory postsynaptic potentials.
Main Results:
- Dopamine augmented GABAB inhibitory postsynaptic potentials (i.p.s.ps) when D2 receptors were blocked.
- D1 agonists mimicked this effect, while D1 antagonists blocked it, confirming D1 receptor involvement.
- D1 receptor modulation was specific to GABAB, not GABAA, and occurred presynaptically.
- D1 antagonists alone reduced GABAB i.p.s.p. amplitude.
Conclusions:
- Dopamine acts tonically on presynaptic D1 receptors located on afferent GABA neuron terminals.
- These receptors selectively facilitate GABAB-mediated neurotransmission in the midbrain.