PT  - JOURNAL ARTICLE
AU  - Khom, S.
AU  - Steinkellner, T.
AU  - Hnasko, T. S.
AU  - Roberto, M.
TI  - Alcohol dependence potentiates substance P/neurokinin-1 receptor signaling in the rat central nucleus of amygdala
AID  - 10.1126/sciadv.aaz1050
DP  - 2020 Mar 01
TA  - Science Advances
PG  - eaaz1050
VI  - 6
IP  - 12
4099  - http://advances.sciencemag.org/content/6/12/eaaz1050.short
4100  - http://advances.sciencemag.org/content/6/12/eaaz1050.full
SO  - Sci Adv2020 Mar 01; 6
AB  - 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 The NK-1R antagonist blocked acute alcohol-induced GABA release in alcohol-dependent and withdrawn but not in naïve rats, indicating that dependence engages the SP/NK-1R system to mediate acute effects of alcohol.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.