Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala.

Abstract:

:Behavioral and clinical studies suggest a critical role of substance P (SP)/neurokinin-1 receptor (NK-1R) signaling in alcohol dependence. Here, we examined regulation of GABA transmission in the medial subdivision of the central amygdala (CeM) by the SP/NK-1R system, and its neuroadaptation following chronic alcohol exposure. In naïve rats, SP increased action potential-dependent GABA release, and the selective NK-1R antagonist L822429 decreased it, demonstrating SP regulation of CeM activity under basal conditions. SP induced a larger GABA release in alcohol-dependent rats accompanied by decreased NK-1R expression compared to naïve controls, suggesting NK-1R hypersensitivity which persisted during protracted alcohol withdrawal. The NK-1R antagonist blocked acute alcohol-induced GABA release in alcohol-dependent and withdrawn but not in naïve rats, indicating that dependence engages the SP/NK-1R system to mediate acute effects of alcohol. Collectively, we report long-lasting CeA NK-1R hypersensitivity corroborating that NK-1Rs are promising targets for the treatment of alcohol use disorder.

journal_name

Sci Adv

journal_title

Science advances

authors

Khom S,Steinkellner T,Hnasko TS,Roberto M

doi

10.1126/sciadv.aaz1050

subject

Has Abstract

pub_date

2020-03-18 00:00:00

pages

eaaz1050

issue

12

issn

2375-2548

pii

aaz1050

journal_volume

6

pub_type

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