title: Chronic administration of morphine is associated with a decrease in surface AMPA GluR1 receptor subunit in dopamine D1 receptor expressing neurons in the shell and non-D1 receptor expressing neurons in the core of the rat nucleus accumbens.
abstract: The nucleus accumbens (Acb) is an extensively studied neuroanatomical substrate of opiate reward and the neural plasticity associated with chronic opioid use. The cellular mechanisms mediating opioid-dependent plasticity are uncertain, however AMPA-type glutamate receptor trafficking in dopamine D1 dopamine receptor (D1R) expressing neurons may be a potential cellular pathway for these adaptations, although there is no evidence for this possibility. Immunogold electron microscopy was used to quantify the surface expression of the AMPA GluR1 subunit in dendritic profiles of neurons in the Acb in response to intermittent 14-day non-contingent injections of escalating doses of morphine, a model that parallels opioid self-administration. To determine if changes in GluR1 trafficking occurred in neurons potentially sensitive to dopamine-induced D1R activation, immunoperoxidase labeling of D1R was combined with immunogold labeling of GluR1. Immunogold quantification was performed in two distinct Acb subregions, the shell, an area involved in processing incentive salience related to rewarding stimuli, and the core, an area involved in reward-seeking behaviors. We provide the first report that chronic morphine administration is associated with a receptor-phenotypic decrease in surface trafficking of GluR1 in Acb subregions. When compared to saline injected animals, morphine produced a decrease in plasma membrane GluR1 labeling in medium- and large-sized D1R expressing dendritic profiles in the Acb shell. In contrast, in the Acb core, surface GluR1 was decreased in small-sized dendrites that did not express the dopamine receptor. These results indicate that chronic intermittent injection of escalating doses of morphine is accompanied by ultrastructural plasticity of GluR1 in neurons that are responsive to glutamate and dopamine-induced D1R activation in the Acb shell, and neurons capable of responding to glutamate but not D1R receptor stimulation in the Acb core. Thus, AMPA receptor trafficking associated with chronic opiate exposure in functionally distinct areas of the Acb may be distinguished by D1R receptor activation, suggesting the potential for differing neural substrates of reward and motor aspects of addictive processes involving glutamate and dopamine signaling.
authors.affiliation: Department of Neurology and Neuroscience, 411 East 69th Street, Well Medical College of Cornell University, NY, NY 10021, USA. mjg2003@mail.med.cornell.edu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Glass
authors.forename: Diane A
authors.initials: DA
authors.lastname: Lane
authors.forename: Eric E O
authors.initials: EE
authors.lastname: Colago
authors.forename: June
authors.initials: J
authors.lastname: Chan
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Schlussman
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Pickel
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004334:Drug Administration Schedule; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009714:Nucleus Accumbens / Q000166:cytology* / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D009020:Morphine; D009294:Narcotics; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1