Quinpirole elicits differential in vivo changes in the pre- and postsynaptic distributions of dopamine D 2 receptors in mouse striatum: Relation to cannabinoid-1 (CB 1) receptor targeting

摘要

Rationale: 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 2Rs) and modulated by activation of the cannabinoid-1 receptor (CB 1R). The dopamine D 2/D3 receptor agonist, quinpirole elicits internalization of D 2Rs in isolated cells; however, dendritic and axonal targeting of D 2Rs may be highly influenced by circuit-dependent changes in vivo and potentially influenced by endogenous CB 1R activation. Objective: We sought to determine whether quinpirole alters the surface/cytoplasmic partitioning of D 2Rs in striatal neurons in vivo. Methods: To address this question, we examined the electron microscopic immunolabeling of D 2 and CB 1 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. Results: Many neuronal profiles throughout the striatum of both treatment groups expressed the D 2R and/or CB 1R. As compared with saline, quinpirole-injected mice showed a significant region-specific decrease in the plasmalemmal and increase in the cytoplasmic density of D 2R-immunogold particles in postsynaptic dendrites without CB 1R-immunolabeling in the Acb shell. However, quinpirole produced a significant increase in the plasmalemmal density of D 2R immunogold in CB 1R negative axons in both the Acb shell and CPu. Conclusions: Our results provide in vivo evidence for agonist-induced D 2R trafficking that is inversely related to CB 1R distribution in postsynaptic neurons of Acb shell and in presynaptic axons in this region and in the CPu.