Quinpirole elicits differential in vivo changes in the pre- and postsynaptic distributions of dopamine D2 receptors in mouse striatum: relation to cannabinoid-1 (CB1) receptor targeting

The nucleus accumbens (Acb) shell and caudate-putamen nucleus (CPu) are respectively implicated in the motivational and motor effects of dopamine, which are mediated in part through dopamine D-2-like receptors (D(2)Rs) and modulated by activation of the cannabinoid-1 receptor (CB1R). The dopamine D-2/D3 receptor agonist, quinpirole elicits internalization of D(2)Rs in isolated cells; however, dendritic and axonal targeting of D(2)Rs may be highly influenced by circuit-dependent changes in vivo and potentially influenced by endogenous CB1R activation. We sought to determine whether quinpirole alters the surface/cytoplasmic partitioning of D(2)Rs in striatal neurons in vivo. To address this question, we examined the electron microscopic immunolabeling of D-2 and CB1 receptors in the Acb shell and CPu of male mice at 1 h following a single subcutaneous injection of quinpirole (0.5 mg/kg) or saline, a time point when quinpirole reduced locomotor activity. Many neuronal profiles throughout the striatum of both treatment groups expressed the D2R and/or CB1R. As compared with saline, quinpirole-injected mice showed a significant region-specific decrease in the plasmalemmal and increase in the cytoplasmic density of D2R-immunogold particles in postsynaptic dendrites without CB1R-immunolabeling in the Acb shell. However, quinpirole produced a significant increase in the plasmalemmal density of D2R immunogold in CB1R negative axons in both the Acb shell and CPu. Our results provide in vivo evidence for agonist-induced D2R trafficking that is inversely related to CB1R distribution in postsynaptic neurons of Acb shell and in presynaptic axons in this region and in the CPu.