Presynaptic dopamine D2-like receptors inhibit excitatory transmission onto rat ventral tegmental dopaminergic neurones.
1. The effects of dopamine (DA) on non-NMDA glutamatergic transmission onto dopaminergic neurones in the ventral tegmental area (VTA) were examined in rat midbrain slices using the whole-cell patch-clamp technique. EPSCs in dopaminergic neurones evoked by focal stimulation within the VTA were reversibly blocked by 5 microM CNQX in the presence of bicuculline (20 microM), strychnine (0.5 microM) and D-amino-5-phosphonopentanoic acid (D-AP5, 25 microM). 2. Bath application of DA reduced the amplitude of EPSCs up to 65.1 +/- 9. 52% in a concentration-dependent manner between 0.3-1000 microM (IC50, 16.0 microM) without affecting the holding current at -60 mV measured using a Cs+-filled electrode. 3. The effect of DA on evoked EPSCs was mimicked by the D2-like receptor agonist quinpirole but not by the D1-like receptor agonist SKF 81297, and was antagonized by the D2-like receptor antagonist sulpiride (KB, 0.96 microM), but not by the D1-like receptor antagonist SCH 23390 (KB, 228.6 microM). 4. Dopamine (30 microM) reduced the mean frequency of spontaneous miniature EPSCs (mEPSCs) without affecting their mean amplitude, and the DA-induced effect on the mEPSCs was dependent on the external Ca2+ concentration. 5. These results suggest that afferent glutamatergic fibres which terminate on VTA dopaminergic neurones possess presynaptic D2-like receptors, activation of which inhibits glutamate release by reducing Ca2+ influx.
Koga
E
E
Department of Physiology, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Momiyama
T
T
D000818:Animals; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000502:physiology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D004298:Dopamine