Presynaptic involvement of nitric oxide in dopamine D1/D5 receptor- induced sustained enhancement of synaptic currents mediated by ionotropic glutamate receptors in the rat hippocampus

Using whole-cell patch-clamp recordings, the study tested the possibility whether nitric oxide (NO) was involved in dopamine D1/D5 receptor (D1/D5r)-induced sustained enhancement of excitatory postsynaptic currents (EPSCs) mediated by ionotropic glutamate receptors in rat hippocampal slices. Activation of D1/D5r by a selective agonist, 50 μM (±)-6-chloro-PB hydrobromide, elicited not only a sustained enhancement but also an increased frequency of spontaneous EPSC. The D1/D5r-induced effect was associated with decreases in paired-pulse facilitation (PPF). A selective inhibitor of neuronal NO synthase (nNOS), 100 μM 7-nitroindazole monosodium salt, substantially attenuated both the magnitudes of D1/D5r-induced enhancement and PPF decrease. These results suggest that presynaptic effects mediated by NO, possibly synthesized by nNOS, are involved in D1/D5-induced sustained enhancement of synaptic currents mediated by ionotropic glutamate receptors in the hippocampus.