title: Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal.
abstract: The central nucleus of the amygdala (CeA) is a crucial component of the neuronal circuitry mediating aversive emotion. Its role in the negative affective states during drug withdrawal includes changes in opioidergic, GABAergic, and corticotropin-releasing factor neurotransmission. However, the modulation of the neurobiological interconnectivity in the CeA and its effects in the negative reinforcement of drug dependents are poorly understood.
  
  
  
  We performed electrophysiological recordings to assess the membrane excitability of parvalbumin (PV)+interneurons in the CeA during chronic morphine withdrawal. We tested the morphine withdrawal-induced negative affective states, such as the aversive (assessed by conditioned place aversion), anxiety (assessed by elevated plus maze), and anhedonic-like (assessed by saccharin preference test) behaviors, as well as the mRNA level of corticotropin-releasing hormone (CRH) via optogenetic inhibition or activation of PV+interneurons in the CeA.
  
  
  
  Chronic morphine withdrawal increased the firing rate of CeA PV+interneurons. Optogenetic inhibition of the activity of CeA PV+interneurons attenuated the morphine withdrawal-induced negative affective states, such as the aversive, anxiety, and anhedonic-like behaviors, while direct activation of CeA PV+interneurons could trigger those negative affective-like behaviors. Optogenetic inhibition of the CeA PV+interneurons during the morphine withdrawal significantly attenuated the elevated CRH mRNA level in the CeA.
  
  
  
  The activity of PV+interneurons in the CeA was up-regulated during chronic morphine withdrawal. The activation of PV+interneurons during morphine withdrawal was crucial for the induction of the negative emotion and the up-regulation of CRH mRNA levels in the CeA.
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Drs L Wang, Ma, F Wang, and Shen, and Mr Jiang); Department of Assisted Reproduction, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China (Dr L Wang).
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Drs L Wang, Ma, F Wang, and Shen, and Mr Jiang); Department of Assisted Reproduction, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China (Dr L Wang).
authors.forename: Minjie
authors.initials: M
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Drs L Wang, Ma, F Wang, and Shen, and Mr Jiang); Department of Assisted Reproduction, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China (Dr L Wang).
authors.forename: Changyou
authors.initials: C
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Drs L Wang, Ma, F Wang, and Shen, and Mr Jiang); Department of Assisted Reproduction, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China (Dr L Wang) lanma@shmu.edu.cn ffwang@fudan.edu.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Drs L Wang, Ma, F Wang, and Shen, and Mr Jiang); Department of Assisted Reproduction, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China (Dr L Wang) lanma@shmu.edu.cn ffwang@fudan.edu.cn.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
mesh_terms: D000339:Affect; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal; D066274:Central Amygdaloid Nucleus / Q000378:metabolism* / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials; D005247:Feeding Behavior; D005838:Genotype; D007395:Interneurons / Q000378:metabolism*; D018782:Maze Learning; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055369:Miniature Postsynaptic Potentials; D009020:Morphine; D062308:Optogenetics; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012439:Saccharin / Q000008:administration & dosage; D015398:Signal Transduction; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D015854:Up-Regulation
chemical_list: D010320:Parvalbumins; D012333:RNA, Messenger; D009020:Morphine; D003346:Corticotropin-Releasing Hormone; D012439:Saccharin
keywords: CRH; PV; central amygdala; morphine withdrawal; negative affective states