Direct evidence that the brain reward system is involved in the control of scratching behaviors induced by acute and chronic itch

Takao Setsu, Yusuke Hamada, Daisuke Oikawa, Tomohisa Mori, Yozo Ishiuji, Daisuke Sato, Michiko Narita, Shogo Miyazaki, Eri Furuta, Yukari Suda, Hiroyasu Sakai, Takahiro Ochiya, Hiroyuki Tezuka, Masako Iseki, Eiichi Inada, Akihiro Yamanaka, Naoko Kuzumaki, Minoru Narita

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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 ΔFosB, 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 ΔFosB 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.

Original languageEnglish
Pages (from-to)624-631
Number of pages8
JournalBiochemical and Biophysical Research Communications
Publication statusPublished - 01-01-2021

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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