title: NMDA and dopamine D1 receptors within NAc-shell regulate IEG proteins expression in reward circuit during cocaine memory reconsolidation.
abstract: Reactivation of consolidated memory initiates a memory reconsolidation process, during which the reactivated memory is susceptible to strengthening, weakening or updating. Therefore, effective interference with the memory reconsolidation process is expected to be an important treatment for drug addiction. The nucleus accumbens (NAc) has been well recognized as a pathway component that can prevent drug relapse, although the mechanism underlying this function is poorly understood. We aimed to clarify the regulatory role of the NAc in the cocaine memory reconsolidation process, by examining the effect of applying different pharmacological interventions to the NAc on Zif 268 and Fos B expression in the entire reward circuit after cocaine memory reactivation. Through the cocaine-induced conditioned place preference (CPP) model, immunohistochemical and immunofluorescence staining for Zif 268 and Fos B were used to explore the functional activated brain nuclei after cocaine memory reactivation. Our results showed that the expression of Zif 268 and Fos B was commonly increased in the medial prefrontal cortex (mPFC), the infralimbic cortex (IL), the NAc-core, the NAc-shell, the hippocampus (CA1, CA2, and CA3 subregions), the amygdala, the ventral tegmental area (VTA), and the supramammillary nucleus (SuM) following memory reconsolidation, and Zif 268/Fos B co-expression was commonly observed (for Zif 268: 51-68%; for Fos B: 52-66%). Further, bilateral NAc-shell infusion of MK 801 and SCH 23390, but not raclopride or propranolol, prior to addictive memory reconsolidation, decreased Zif 268 and Fos B expression in the entire reward circuit, except for the amygdala, and effectively disturbed subsequent CPP-related behavior. In summary, N-methyl-d-aspartate (NMDA) and dopamine D1 receptors, but not dopamine D2 or β adrenergic receptors, within the NAc-shell, may regulate Zif 268 and Fos B expression in most brain nuclei of the reward circuit after cocaine memory reactivation. These findings indicated that the NAc played a key role in regulating addictive memory reconsolidation by influencing the function of the entire addictive memory network.
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China. Electronic address: gesn8561@fmmu.edu.cn.
authors.forename: S
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China.
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province 210002, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, PR China. Electronic address: tdwxlian@126.com.
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D017781:Genes, Immediate-Early / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
chemical_list: D001552:Benzazepines; D018765:Dopamine Uptake Inhibitors; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D018377:Neurotransmitter Agents; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; C534628:SCH 23390; D020891:Raclopride; D016291:Dizocilpine Maleate; D011433:Propranolol; D003042:Cocaine
keywords: IEG; MK 801; SCH 23390; memory reconsolidation; reward circuit; the NAc