Differential effects of aprepitant, a clinically used neurokinin-1 receptor antagonist on the expression of conditioned psychostimulant versus opioid reward.
Differential effects of aprepitant, a clinically used neurokinin-1 receptor antagonist on the expression of conditioned psychostimulant versus opioid reward.
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临床使用的神经蛋白-1受体拮抗剂Aprepitant的差异作用对条件精神刺激剂与阿片类药物奖励的表达。
DOI：
10.1007/s00213-016-4504-6
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发表时间：
2017-02
影响因子：
3.4
通讯作者：
Jayanthi LD
中科院分区：
文献类型：
--
作者：
Mannangatti P;Sundaramurthy S;Ramamoorthy S;Jayanthi LD
神经激肽-1受体（NK 1 R）信号调节与精神兴奋剂和阿片类药物相关的行为。精神兴奋剂，如安非他明（AMPH）和可卡因，结合到单胺转运蛋白，并改变其功能。多巴胺和去甲肾上腺素转运蛋白均受NK 1 R激活的调节，这表明NK 1 R介导的儿茶酚胺转运蛋白在精神兴奋剂介导的行为中的调节作用。在C57 BL/6 J小鼠中检查了阿瑞匹坦（10 mg/kg）体内给药对AMPH（0.5和2 mg/kg）和可卡因（5和20 mg/kg）诱导的条件性位置偏爱（CPP）表达以及运动激活的影响。还检查了阿瑞匹坦对吗啡（1和5 mg/kg）诱导的CPP的作用，以鉴定阿瑞匹坦对精神兴奋剂与阿片样物质诱导的行为的特异性作用。阿瑞匹坦给药显著减弱了由AMPH和可卡因产生的CPP表达和运动激活。与此相反，阿瑞匹坦显着增强吗啡产生的CPP的表达，同时显着抑制吗啡条件小鼠的自发活动。阿瑞匹坦本身不诱导显著的CPP或条件性位置厌恶或运动激活或抑制。AMPH或可卡因诱导的CPP和阿瑞匹坦的自发激活的衰减表明NK 1 R信号传导在精神兴奋剂介导的行为中的作用。吗啡诱导的CPP表达的刺激和吗啡条件小鼠的自发活动的抑制表明NK 1 R拮抗剂对条件性精神兴奋剂与阿片奖励的不同作用。总之，这些研究结果表明，临床上使用的NK 1 R拮抗剂阿瑞匹坦可能作为一种潜在的治疗药物在治疗精神兴奋剂滥用。
Neurokinin-1 receptor (NK1R) signaling modulates behaviors associated with psychostimulants and opioids. Psychostimulants, such as amphetamine (AMPH) and cocaine, bind to monoamine transporters, and alter their functions. Both dopamine and norepinephrine transporters are regulated by NK1R activation suggesting a role for NK1R mediated catecholamine transporter regulation in psychostimulant-mediated behaviors. The effect of in vivo administration of aprepitant (10 mg/kg) on the expression of AMPH (0.5 and 2 mg/kg) and cocaine (5 and 20 mg/kg) induced conditioned place preference (CPP) as well as locomotor activation was examined in C57BL/6J mice. The effect of aprepitant on morphine (1 and 5 mg/kg) induced CPP was also examined to identify the specific actions of aprepitant on psychostimulant versus opioid induced behaviors. Aprepitant administration significantly attenuated the CPP expression and locomotor activation produced by AMPH and cocaine. In contrast, aprepitant significantly enhanced the expression of CPP produced by morphine while significantly suppressing the locomotor activity of the mice conditioned with morphine. Aprepitant by itself did not induce significant CPP or conditioned place aversion or locomotor activation or suppression. Attenuation of AMPH or cocaine induced CPP and locomotor activation by aprepitant suggests a role for NK1R signaling in psychostimulant-mediated behaviors. Stimulation of morphine induced CPP expression and suppression of locomotor activity of morphine conditioned mice suggest differential effects of NK1R antagonism on conditioned psychostimulant versus opioid reward. Collectively, these findings indicate that clinically used NK1R antagonist, aprepitant may serve as a potential therapeutic agent in the treatment of psychostimulant abuse.