Presynaptic dopamine D2‐like receptors inhibit excitatory transmission onto rat ventral tegmental dopaminergic neurones

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Abstract
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 μM CNQX in the presence of bicuculline (20 μM), strychnine (0.5 μM) and D-amino-5-phosphonopentanoic acid (D-AP5, 25 μM). Bath application of DA reduced the amplitude of EPSCs up to 65.1 ± 9.52% in a concentration-dependent manner between 0.3-1000 μM (IC50, 16.0 μM) without affecting the holding current at −60 mV measured using a Cs+-filled electrode. 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 μM), but not by the D1-like receptor antagonist SCH 23390 (KB, 228.6 μM). Dopamine (30 μM) 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. 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.