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

• Published in: Psychopharmacologia 2012-05, Vol.221 (1), p.101-113
• Main Authors: Lane, Diane A., Chan, June, Fitzgerald, Megan L., Kearn, Chris S., Mackie, Ken, Pickel, Virginia M.
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - ultrastructure; Drug addiction; Male; Medical sciences; Mice; Mice, Inbred C57BL; Motor Activity - drug effects; Neurons - metabolism; Neurons - ultrastructure; Neurosciences; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Original Investigation; Pharmacology/Toxicology; Post-Synaptic Density - metabolism; Presynaptic Terminals - metabolism; Protein Transport - drug effects; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Quinpirole - pharmacology; Receptor, Cannabinoid, CB1 - metabolism; Receptors, Dopamine D2 - metabolism
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-011-2553-4

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 2 Rs) and modulated by activation of the cannabinoid-1 receptor (CB 1 R). 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 CB 1 R activation. Objective We sought to determine whether quinpirole alters the surface/cytoplasmic partitioning of D 2 Rs 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 2 R and/or CB 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 2 R-immunogold particles in postsynaptic dendrites without CB 1 R-immunolabeling in the Acb shell. However, quinpirole produced a significant increase in the plasmalemmal density of D 2 R immunogold in CB 1 R negative axons in both the Acb shell and CPu. Conclusions Our results provide in vivo evidence for agonist-induced D 2 R trafficking that is inversely related to CB 1 R distribution in postsynaptic neurons of Acb shell and in presynaptic axons in this region and in the CPu.