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

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