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 The NK-1R antagonist blocked acute alcohol-induced GABA release in alcohol-dependent and withdrawn but not in naïve rats, indicating that dependence engages the SP/NK-1R system to mediate acute effects of alcohol.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.