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

Abstract

RationaleThe 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 D2-like receptors (D2Rs) and modulated by activation of the cannabinoid-1 receptor (CB1R). The dopamine D2/D3 receptor agonist, quinpirole elicits internalization of D2Rs in isolated cells; however, dendritic and axonal targeting of D2Rs may be highly influenced by circuit-dependent changes in vivo and potentially influenced by endogenous CB1R activation.ObjectiveWe sought to determine whether quinpirole alters the surface/cytoplasmic partitioning of D2Rs in striatal neurons in vivo.MethodsTo address this question, we examined the electron microscopic immunolabeling of D2 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.ResultsMany 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.ConclusionsOur 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.