Robust modulation of [3H]dopamine release from rat striatal slices by D-2 dopamine receptors

Conflicting results have been reported for D-2 dopamine (DA) receptor modulation of DA release from rat striatal slices. After systematic examination of the assay conditions used to evoke release of [3H]DA, we report robust modulation of calcium-dependent stimulation-evoked 3H-overflow by D-2 receptors in rat striatal slices preloaded with [3H]DA. In the presence of the DA uptake inhibitor, nomifensine, the amount of 3H-overflow evoked by low numbers (15-30) of pulses was not dependent on the frequency of stimulation (0.25-3.0 Hz). When larger numbers (60-300) of pulses were applied, 3H-overflow was related inversely to the frequency of stimulation. In contrast, 3H-overflow increased linearly as the total number of pulses applied was increased when examined at any of these frequencies. Nomifensine (10 microM) augmented 3H-overflow at each level of stimulation while only slightly increasing spontaneous release. Modulation of evoked 3H-overflow by S-sulpiride, a selective D-2 DA receptor antagonist, was dependent on the number of pulses delivered, rather than on the frequency of stimulation. In contrast, modulation by pergolide, a selective D-2 DA receptor agonist, was dependent on stimulation frequency. S-sulpiride produced greater augmentation of 3H-overflow after delivery of low numbers of pulses in the presence of nomifensine. However, pergolide produced greater inhibition of 3H-overflow at low frequencies of stimulation in the absence of nomifensine. These results indicate that D-2 receptors in rat striatum modulate DA release and are most effective when a low concentration of endogenous DA is present in the synaptic cleft.