Multiple actions of a D3 dopamine receptor agonist, PD128907, on GABAergic inhibitory transmission between medium spiny neurons in mouse nucleus accumbens shell

•Roles of D3 receptors in synaptic modulation in the nucleus accumbens are characterized.•PD128907, a D3 receptor agonist, mainly suppress GABAergic transmission.•A presynaptic mechanism underlies the inhibitory action of PD128907.•D2/D3 receptor ensemble regulates the lateral inhibition in this nucleus. The nucleus accumbens (NAc) plays a crucial role in pathophysiological responses, such as reward-related behaviors, addiction, depression and schizophrenia, through activation of dopaminergic system in the midbrain area. Principal cells in the NAc are medium spiny neurons (MSNs), which constitute the majority (90–95%) of NAc neuron populations in rodents. MSNs are mutually connected to form networks of lateral inhibition. Our previous study showed that activation of D2-like receptors presynaptically inhibited GABAergic transmission between MSN–MSN connections in the NAc. D2-like receptors in MSNs have been reported to consist of D2 and D3 receptors, but their functional roles remain to be elucidated. This study, therefore, aimed at examining the effects of D3 receptor activation on MSN–MSN connections using PD128907, a preferential D3 dopamine receptor agonist, and whole cell recordings from MSNs in acute slices including the NAc. In more than half of cells tested, PD128907 reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in a concentration-dependent manner. However, the agonist caused multiple actions, namely, decrease, increase and no significant changes, in the amplitude as well as the frequency of sIPSCs in individual cells. Our data, together with the results from previous studies, show that dopamine could suppress GABAergic transmission, i.e., lateral inhibition between some of MSNs, via activation of both D2 and D3 receptors.