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 mu M CNQX in the presence of bicuculline (20 mu M), strychnine (0.5 mu M) and D-amino-5-phosphonopentanoic acid (D-AP5, 25 mu M). 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 mu M (IC50, 16.0 mu M) 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 D-2-like receptor agonist quinpirole but not by the D-1-like receptor agonist SKF 81297, and was antagonized by the D-2-like receptor antagonist sulpiride (K-B, 0.96 mu M), but not by the D-1-like receptor antagonist SCH 23390 (K-B, 228.6 mu M). 4. Dopamine (30 mu M) reduced the mean frequency of spontaneous miniature EPSCs (mEPSCs) without affecting their mean amplitude, and the DB-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 D-2-like receptors, activation of which inhibits glutamate release by reducing Ca2+ influx.