title: Extinction of opiate reward reduces dendritic arborization and c-Fos expression in the nucleus accumbens core.
abstract: Recurrent opiate use combined with environmental cues, in which the drug was administered, provokes cue-induced drug craving and conditioned drug reward. Drug abuse craving is frequently linked with stimuli from a prior drug-taking environment via classical conditioning and associative learning. We modeled the conditioned morphine reward process by using acquisition and extinction of conditioned place preference (CPP) in C57BL/6 mice. Mice were trained to associate a morphine injection with a drug context using a classical conditioning paradigm. In morphine conditioning (0, 0.25, 0.5, 1, 5, or 10 mg/kg) experimental mice acquired a morphine CPP dose response with 10mg/kg as most effective. During morphine CPP extinction experiments, mice were divided into three test groups: morphine CPP followed by extinction training, morphine CPP followed by sham extinction, and saline controls. Extinction of morphine CPP developed within one extinction experiment (4 days) that lasted over two more trials (another 8 days). However, the morphine CPP/sham extinction group retained a place preference that endured through all three extinction trials. Brains were harvested following CPP extinction and processed using Golgi-Cox impregnation. Changes in dendritic morphology and spine quantity were examined in the nucleus accumbens (NAc) Core and Shell neurons. In the NAcCore only, morphine CPP/extinguished mice produced less dendritic arborization, and a decrease in neuronal activity marker c-Fos compared to the morphine CPP/sham extinction group. Extinction of morphine CPP is associated with decreased structural complexity of dendrites in the NAcCore and may represent a substrate for learning induced structural plasticity relevant to addiction.
authors.affiliation: Research Service, VA Boston Healthcare System, 150 South Huntington Ave, Boston, Massachusetts, 02130, USA; Department of Psychiatry, Boston University School of Medicine, 720 Harrison Avenue, Boston, Massachusetts, 02118, USA; Department of Pharmacology and Experimental Therapeutics, 72 East Concord Street, Boston University School of Medicine, Boston, Massachusetts, 02118, USA. Electronic address: kleitemo@bu.edu.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Leite-Morris
authors.affiliation: Research Service, VA Boston Healthcare System, 150 South Huntington Ave, Boston, Massachusetts, 02130, USA; Department of Pharmacology and Experimental Therapeutics, 72 East Concord Street, Boston University School of Medicine, Boston, Massachusetts, 02118, USA. Electronic address: kendrak@bu.edu.
authors.forename: Kendra L
authors.initials: KL
authors.lastname: Kobrin
authors.affiliation: Research Service, VA Boston Healthcare System, 150 South Huntington Ave, Boston, Massachusetts, 02130, USA. Electronic address: marsha.guy@gmail.com.
authors.forename: Marsha D
authors.initials: MD
authors.lastname: Guy
authors.affiliation: Research Service, VA Boston Healthcare System, 150 South Huntington Ave, Boston, Massachusetts, 02130, USA. Electronic address: angela.pieroniyoung@facebook.com.
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Young
authors.affiliation: Research Service, VA Boston Healthcare System, 150 South Huntington Ave, Boston, Massachusetts, 02130, USA. Electronic address: Stephen.Heinrichs@va.gov.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Heinrichs
authors.affiliation: Research Service, VA Boston Healthcare System, 150 South Huntington Ave, Boston, Massachusetts, 02130, USA; Mental Health Service, VA Boston Healthcare System, 150 South Huntington Ave, Boston, Massachusetts, 02130, USA; Department of Psychiatry, Boston University School of Medicine, 720 Harrison Avenue, Boston, Massachusetts, 02118, USA; Department of Pharmacology and Experimental Therapeutics, 72 East Concord Street, Boston University School of Medicine, Boston, Massachusetts, 02118, USA. Electronic address: Gary.Kaplan@va.gov.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects; D003712:Dendrites / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D049229:Dendritic Spines / Q000473:pathology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009293:Opioid-Related Disorders / Q000473:pathology / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012201:Reward; D013028:Space Perception / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000473:pathology / Q000503:physiopathology
chemical_list: D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D009020:Morphine
keywords: Conditioned place preference extinction; Dendrite; Morphine; Nucleus accumbens; Structural plasticity