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Neurokinin receptors in drug and alcohol addiction

机译：药物和酒精成瘾中的神经激素受体

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The neurokinins are a class of peptide signaling molecules that mediate a range of central and peripheral functions including pain processing, gastrointestinal function, stress responses, and anxiety. Recent data have linked these neuropeptides with drug-related behaviors. Specifically, substance P (SP) and neurokinin B (NKB), have been shown to influence responses to alcohol, cocaine, and/or opiate drugs. SP and NKB preferentially bind to the neurokinin-1 receptor (NK1R) and neurokinin-3 receptor (NK3R), respectively, but do have some affinity for all classes of neurokinin receptor at high concentrations. NK1R activity has been shown to influence reward and reinforcement for opiate drugs, stimulatory and neurochemical responses to cocaine, and escalated and stress-induced alcohol seeking. In reinstatement models of relapse-like behavior, NK1R antagonism attenuates stress-induced reinstatement for all classes of drugs tested to date. The NK3R also influences alcohol intake and behavioral/neurochemical responses to cocaine, but less research has been performed in regard to this particular receptor in preclinical models of addiction. Clinically, agents targeting these receptors have shown some promise, but have produced mixed results. Here, the preclinical findings for the NK1R and NK3R are reviewed, and discussion is provided to interpret clinical findings. Additionally, important factors to consider in regards to future clinical work are suggested.
机译：Neurokinins是一类肽信号分子，介导一系列中央和外周功能，包括疼痛加工，胃肠功能，应力反应和焦虑。最近的数据与药物相关的行为联系着这些神经肽。具体地，已经证明了物质p（sp）和神经蛋白酶b（nkb）对醇，可卡因和/或阿片药物的反应影响。 SP和NKB分别优先与神经激素-1受体（NK1R）和神经喹啉-3受体（NK3R）结合，但确实对高浓度的所有类神经激素受体具有一些亲和力。已显示NK1R活动对可卡因的奖励药物，刺激和神经化学反应的奖励和加固影响，并且升级和应激诱导的酒精求寻求。在复发样行为的恢复模型中，NK1R拮抗剂衰减对迄今为止测试所有类别的药物恢复恢复。 NK3R还影响对可卡因的酒精摄入和行为/神经化学反应，但在临床前模型中对该特定受体进行了较少的研究。临床上，靶向这些受体的药剂表现出一些承诺，但已经产生了混合结果。这里，审查NK1R和NK3R的临床前发现，并提供讨论以解释临床发现。此外，提出了考虑未来临床工作的重要因素。

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