Cocaine withdrawal-induced trafficking of delta-opioid receptors in rat nucleus accumbens.
Interactions between the opioidergic and dopaminergic systems in the nucleus accumbens (NAcb) play a critical role in mediating cocaine withdrawal-induced effects on cell signaling and behavior. In support of this, increased activation of striatal dopamine-D1 receptors (D1R) results in desensitization of delta-opioid receptor (DOR) signaling through adenylyl cyclase during early cocaine withdrawal. A potential cellular substrate underlying receptor desensitization is receptor internalization. The present study examined the effect of cocaine withdrawal on subcellular localization of DOR in dendrites of the NAcb core (NAcbC) and shell (NAcbS) using immunoelectron microscopy. Female and male rats received binge-pattern cocaine or saline for 14 days and subsequently underwent 48 h withdrawal. Animals were transcardially perfused and tissue sections were processed for immunogold-silver localization of DOR. Semi-quantitative analysis revealed that cocaine withdrawal caused an increase in the percentage of DOR localized intracellularly in the NAcbS of male and female rats and the NAcbC of male rats compared to saline controls. In contrast, in the NAcbC of female rats, there was an increase in DOR associated with the plasma membrane following cocaine withdrawal. To determine whether modulation of D1R could directly impact DOR containing neurons, the hypothesis that DOR and D1R co-exist in common neurons of the NAcb was examined in naïve rats. Semi-quantitative analysis revealed a subset of profiles containing both DOR and D1R immunoreactivities. The present findings demonstrate a redistribution of DOR in the NAcb following cocaine withdrawal and provide anatomical evidence supporting D1R regulation of DOR function in a subset of NAcb neurons.
Ambrose-Lanci
Lisa M
LM
Farber Institute for Neurosciences, Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA 19107, USA. lisa.ambrose@jefferson.edu
Peiris
Niluk B
NB
Unterwald
Ellen M
EM
Van Bockstaele
Elisabeth J
EJ
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D016253:Microscopy, Immunoelectron; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D012727:Sex Characteristics; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects
D018765:Dopamine Uptake Inhibitors; D017465:Receptors, Opioid, delta; D003042:Cocaine