title: Differential expression of Arc in the mesocorticolimbic system is involved in drug and natural rewarding behavior in rats.
abstract: OBJECTIVE
  To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning.
  
  
  METHODS
  Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously.
  
  
  RESULTS
  Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration.
  
  
  CONCLUSIONS
  The VLS is likely to be critically involved in drug-seeking behavior. The NMDA- and D1 receptor-dependent Arc expression is important in drug-seeking behavior.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Li
authors.forename: Wen-jie
authors.initials: WJ
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: Wang
authors.forename: Jing-gen
authors.initials: JG
authors.lastname: Liu
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D003932:Heroin / Q000008:administration & dosage*; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology; D012201:Reward; D012646:Self Administration
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D017447:Receptors, Dopamine D1; C092069:activity regulated cytoskeletal-associated protein; D016202:N-Methylaspartate; D003932:Heroin