title: 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: BACKGROUND
  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 D₂-like receptors (D₂Rs) and modulated by activation of the cannabinoid-1 receptor (CB₁R). The dopamine D(₂/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.
  
  
  OBJECTIVE
  We sought to determine whether quinpirole alters the surface/cytoplasmic partitioning of D₂Rs in striatal neurons in vivo.
  
  
  METHODS
  To 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology and Neuroscience, Weill-Cornell Medical College, New York, NY 10065, USA.
authors.forename: Diane A
authors.initials: DA
authors.lastname: Lane
authors.forename: June
authors.initials: J
authors.lastname: Chan
authors.forename: Megan L
authors.initials: ML
authors.lastname: Fitzgerald
authors.forename: Chris S
authors.initials: CS
authors.lastname: Kearn
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Pickel
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D057907:Post-Synaptic Density / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects*; D019257:Quinpirole / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D043884:Receptor, Cannabinoid, CB1; D017448:Receptors, Dopamine D2; D019257:Quinpirole