Analysis of function of dopamine as a retrograde messenger in the basal ganglia

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Whole-cell patch-clamp study was carried out to elucidate physiological roles of dopamine (DA) using midbrain slices of the mice (P13-21). EPSCs mediated by non-NMDA glutamate receptors were evoked in the ventral tegmental dopaminergic neurons by focal stimulation at the holding potential of -60 mV. Application of a depolarizing pulse to 0 mV for 5 s inhibited the EPSCs by 42.8 ± 3.1% (n=16) in wild type mice. The magnitude of depolarization-induced inhibition of EPSCs (DSE) was significantly (P<0.05) reduced to 7.3 ± 9.9% (n=5) in the presence of a D2-like receptor antagonist, sulpiride (5 μM), in the bathing solution. DSE amplitude was also significantly (P<0.05) small in slices obtained from D2 receptor deficient mice (7.3 ± 2.0%, n=17). DSE was also observed by action potential generation induced by depolarizing pulses in the current-clamp mode (36.5 ± 5.9%, n=5). These results suggest that DA released from dopaminergic neurons acts on presynaptic D2 receptors to inhibit glutamate release, implying a role of DA as a retrograde messenger in the central nervous system.