Lack of self-administration and behavioural sensitisation to morphine, but not cocaine, in mice lacking NK1 receptors
Lack of self-administration and behavioural sensitisation to morphine, but not cocaine, in mice lacking NK1 receptors
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DOI：
10.1016/s0028-3908(02)00295-2
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发表时间：
2002-12-01
影响因子：
4.7
通讯作者：
Stephens, DN
中科院分区：
文献类型：
--
作者：
Ripley, TL;Gadd, CA;Stephens, DN
缺乏NK 1受体（P物质的首选受体）的小鼠在热板试验中对吗啡表现出正常的镇痛反应，但根据条件性位置偏爱研究，已预测其对阿片类药物的奖励性质不敏感。在这项研究中，在缺乏NK 1基因的小鼠（NK 1敲除小鼠，NK 1（-/-））中研究了吗啡和可卡因的自我给药以及运动致敏的发展和维持。野生型和NK 1（-/-）小鼠都学会了操作性的应激反应来获得食物。当静脉输注吗啡（0.2 mg/kg/输注）代替食物奖励时，野生型小鼠最初降低了杠杆按压率，但随后增加了奖励杠杆的按压率，以获得约100 mg/kg的奖励。每90分钟10次输注;相比之下，NK 1（-/-）小鼠继续以低速率操作奖励和非奖励杠杆。此外，重复给药后，NK 1（-/-）小鼠对吗啡（15 mg/kg，i. p.）的运动刺激作用不敏感。这些缺陷是阿片类药物特有的，因为NK 1（-/-）小鼠对食物或可卡因自我给药（0.65 mg/kg/输注）的反应与野生型没有差异，并且它们对重复可卡因给药（10 mg/kg，i. p.）表现出正常的行为敏感性。这些结果表明，NK 1受体是至关重要的吗啡的增强性能，并为适应性反应引起的重复阿片类药物给药。据推测，P物质和NK 1受体可能是阿片类药物的发展所必需的，但不是可卡因成瘾。(C)2002爱思唯尔科技有限公司版权所有。
Mice lacking the NK1 receptor, the preferred receptor for substance P, demonstrate normal analgesic responses to morphine on the hot plate assay, but have been predicted, on the basis of conditioned place preference studies, to be insensitive to the rewarding properties of opiates. In this study, self-administration and the development and maintenance of locomotor sensitisation of both morphine and cocaine were investigated in mice that lacked the NK1 gene (NK1 knockout mice, NK1(-/-)). Both, wildtype and NK1(-/-) mice learned an operant lever-press response to obtain food. When intravenous infusions of morphine (0.2 mg/kg/infusion) were substituted for the food reward, the wildtype mice initially reduced rates of lever pressing, but then increased them on the rewarded lever to obtain approx. 10 infusions per 90 min session; in contrast, NK1(-/-) mice continued to operate both the rewarded, and non-rewarded levers at low rates. Additionally, NK1(-/-) mice failed, following repeated administration, to sensitise to the locomotor stimulant effects of morphine (15 mg/kg, i.p.). These deficits were specific to opiates, since NK1(-/-) mice responding for food or cocaine self-administration (0.65 mg/kg/infusion) did not differ from wildtypes, and they showed normal behavioural sensitisation to repeated cocaine administration (10 mg/kg, i.p.). These results demonstrate that NK1 receptors are critical for the reinforcing properties of morphine, and for adaptive responses elicited by repeated opiate administration. It is postulated that substance P and the NK1 receptor may be necessary for the development of opiate, but not cocaine addiction. (C) 2002 Elsevier Science Ltd. All rights reserved.