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

Abstract：

: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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Setsu T,Hamada Y,Oikawa D,Mori T,Ishiuji Y,Sato D,Narita M,Miyazaki S,Furuta E,Suda Y,Sakai H,Ochiya T,Tezuka H,Iseki M,Inada E,Yamanaka A,Kuzumaki N,Narita M

doi

10.1016/j.bbrc.2020.11.030

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

624-631

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)32067-2

journal_volume

534

pub_type

杂志文章

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