PMID- 33220930
OWN - NLM
STAT- MEDLINE
DCOM- 20210419
LR  - 20210419
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 534
DP  - 2021 Jan 1
TI  - Direct evidence that the brain reward system is involved in the control of 
      scratching behaviors induced by acute and chronic itch.
PG  - 624-631
LID - S0006-291X(20)32067-2 [pii]
LID - 10.1016/j.bbrc.2020.11.030 [doi]
AB  - In the present study, we demonstrated that there is a direct relationship between 
      scratching behaviors induced by itch and functional changes in the brain reward 
      system. Using a conditional place preference test, the rewarding effect was 
      clearly evoked by scratching under both acute and chronic itch stimuli. The 
      induction of DeltaFosB, a member of the Fos family of transcription factors, was 
      observed in dopamine transporter (DAT)-positive dopamine neurons in the ventral 
      tegmental area (VTA) of mice suffering from a chronic itch sensation. Based on a 
      cellular analysis of scratching-activated neurons, these neurons highly expressed 
      tyrosine hydroxylase (TH) and DAT genes in the VTA. Furthermore, in an in vivo 
      microdialysis study, the levels of extracellular dopamine in the nucleus 
      accumbens (NAcc) were significantly increased by transient scratching behaviors. 
      To specifically suppress the mesolimbic dopaminergic pathway using 
      pharmacogenetics, we used the TH-cre/hM4Di mice. Pharmacogenetic suppression of 
      mesolimbic dopaminergic neurons significantly decreased scratching behaviors. 
      Under the itch condition with scratching behaviors restricted by an Elizabethan 
      collar, the induction of DeltaFosB was found mostly in corticotropin-releasing 
      hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus 
      (PVN). These findings suggest that repetitive abnormal scratching behaviors under 
      acute and chronic itch stimuli may activate mesolimbic dopamine neurons along 
      with pleasant emotions, while the restriction of such scratching behaviors may 
      initially induce the activation of PVN-CRH neurons associated with stress.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Setsu, Takao
AU  - Setsu T
AD  - Department of Anesthesiology and Pain Medicine, Juntendo University School of 
      Medicine, Tokyo, Japan; Department of Pharmacology, Hoshi University School of 
      Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
FAU - Hamada, Yusuke
AU  - Hamada Y
AD  - Department of Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan; Division of Cancer Pathophysiology, 
      National Cancer Center Research Institute, Tokyo, Japan.
FAU - Oikawa, Daisuke
AU  - Oikawa D
AD  - Department of Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan.
FAU - Mori, Tomohisa
AU  - Mori T
AD  - Department of Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan.
FAU - Ishiuji, Yozo
AU  - Ishiuji Y
AD  - Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
FAU - Sato, Daisuke
AU  - Sato D
AD  - Department of Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan.
FAU - Narita, Michiko
AU  - Narita M
AD  - Division of Cancer Pathophysiology, National Cancer Center Research Institute, 
      Tokyo, Japan; Department of Molecular and Cellular Medicine, Institute of Medical 
      Science, Tokyo Medical University, Tokyo, Japan.
FAU - Miyazaki, Shogo
AU  - Miyazaki S
AD  - Department of Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan.
FAU - Furuta, Eri
AU  - Furuta E
AD  - Department of Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan.
FAU - Suda, Yukari
AU  - Suda Y
AD  - Department of Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan; Division of Cancer Pathophysiology, 
      National Cancer Center Research Institute, Tokyo, Japan.
FAU - Sakai, Hiroyasu
AU  - Sakai H
AD  - Department of Biomolecular Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan.
FAU - Ochiya, Takahiro
AU  - Ochiya T
AD  - Department of Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan; Department of Molecular and Cellular 
      Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
FAU - Tezuka, Hiroyuki
AU  - Tezuka H
AD  - Department of Cellular Function Analysis, Research Promotion and Support 
      Headquarters, Fujita Health University, Aichi, Japan.
FAU - Iseki, Masako
AU  - Iseki M
AD  - Department of Anesthesiology and Pain Medicine, Juntendo University School of 
      Medicine, Tokyo, Japan.
FAU - Inada, Eiichi
AU  - Inada E
AD  - Department of Anesthesiology and Pain Medicine, Juntendo University School of 
      Medicine, Tokyo, Japan.
FAU - Yamanaka, Akihiro
AU  - Yamanaka A
AD  - Department of Neuroscience II, Research Institute of Environmental Medicine, 
      Nagoya University, Aichi, Japan.
FAU - Kuzumaki, Naoko
AU  - Kuzumaki N
AD  - Department of Pharmacology, Hoshi University School of Pharmacy and 
      Pharmaceutical Sciences, Tokyo, Japan. Electronic address: 
      n-kuzumaki@hoshi.ac.jp.
FAU - Narita, Minoru
AU  - Narita M
AD  - Department of Anesthesiology and Pain Medicine, Juntendo University School of 
      Medicine, Tokyo, Japan; Department of Pharmacology, Hoshi University School of 
      Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; Division of Cancer 
      Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan. 
      Electronic address: narita@hoshi.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20201119
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 820484N8I3 (Histamine)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - Z4ZG7O5SZ9 (Picryl Chloride)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Chronic Disease
MH  - Dopamine Plasma Membrane Transport Proteins/genetics/metabolism
MH  - Dopaminergic Neurons/metabolism
MH  - Gene Expression
MH  - Histamine/administration & dosage
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Nucleus Accumbens/physiopathology
MH  - Pharmacogenomic Testing
MH  - Picryl Chloride/administration & dosage
MH  - Pruritus/genetics/*physiopathology/*psychology
MH  - *Reward
MH  - Tyrosine 3-Monooxygenase/genetics
MH  - Ventral Tegmental Area/*physiopathology
OTO - NOTNLM
OT  - Corticotropin-releasing hormone
OT  - Dopamine
OT  - Itch
OT  - Paraventricular nucleus
OT  - Scratching behavior
OT  - Ventral tegmental area
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/11/23 06:00
MHDA- 2021/04/20 06:00
CRDT- 2020/11/22 20:30
PHST- 2020/11/03 00:00 [received]
PHST- 2020/11/09 00:00 [accepted]
PHST- 2020/11/23 06:00 [pubmed]
PHST- 2021/04/20 06:00 [medline]
PHST- 2020/11/22 20:30 [entrez]
AID - S0006-291X(20)32067-2 [pii]
AID - 10.1016/j.bbrc.2020.11.030 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2021 Jan 1;534:624-631. doi: 
      10.1016/j.bbrc.2020.11.030. Epub 2020 Nov 19.