Cannella Nazzareno, Borruto Anna Maria, Petrella Michele, Micioni Di Bonaventura Maria Vittoria, Soverchia Laura, Cifani Carlo, De Carlo Sara, Domi Esi, Ubaldi Massimo
School of Pharmacy, University of Camerino, Via Madonna delle Carceri 9, 62032 Camerino, Italy.
Pharmaceuticals (Basel). 2022 Jun 27;15(7):800. doi: 10.3390/ph15070800.
The neuropeptide S (NPS) is the endogenous ligand of the NPS receptor (NPSR). The NPSR is widely expressed in brain regions that process emotional and affective behavior. NPS possesses a unique physio-pharmacological profile, being anxiolytic and promoting arousal at the same time. Intracerebroventricular NPS decreased alcohol consumption in alcohol-preferring rats with no effect in non-preferring control animals. This outcome is most probably linked to the anxiolytic properties of NPS, since alcohol preference is often associated with high levels of basal anxiety and intense stress-reactivity. In addition, NPSR mRNA was overexpressed during ethanol withdrawal and the anxiolytic-like effects of NPS were increased in rodents with a history of alcohol dependence. In line with these preclinical findings, a polymorphism of the NPSR gene was associated with anxiety traits contributing to alcohol use disorders in humans. NPS also potentiated the reinstatement of cocaine and ethanol seeking induced by drug-paired environmental stimuli and the blockade of NPSR reduced reinstatement of cocaine-seeking. Altogether, the work conducted so far indicates the NPS/NPSR system as a potential target to develop new treatments for alcohol and cocaine abuse. An NPSR agonist would be indicated to help individuals to quit alcohol consumption and to alleviate withdrawal syndrome, while NPSR antagonists would be indicated to prevent relapse to alcohol- and cocaine-seeking behavior.
神经肽 S（NPS）是 NPS 受体（NPSR）的内源性配体。NPSR 在处理情绪和情感行为的脑区广泛表达。NPS 具有独特的生理药理学特征，兼具抗焦虑和促进觉醒的作用。脑室内注射 NPS 可减少偏爱酒精大鼠的酒精摄入量，而对非偏爱酒精的对照动物无影响。这一结果很可能与 NPS 的抗焦虑特性有关，因为酒精偏爱通常与高水平的基础焦虑和强烈的应激反应性相关。此外，在乙醇戒断期间 NPSR mRNA 过度表达，并且在有酒精依赖史的啮齿动物中，NPS 的抗焦虑样作用增强。与这些临床前研究结果一致，NPSR 基因的多态性与导致人类酒精使用障碍的焦虑特质相关。NPS 还增强了由药物配对环境刺激诱导的可卡因和乙醇觅药行为的恢复，而阻断 NPSR 则减少了可卡因觅药行为的恢复。总之，迄今为止所开展的研究表明，NPS/NPSR 系统是开发酒精和可卡因滥用新治疗方法的潜在靶点。NPSR 激动剂可用于帮助个体戒酒并缓解戒断综合征，而 NPSR 拮抗剂可用于预防复发性酒精和可卡因觅药行为。
