Effect of intrathecal pretreatment with the neurokinin receptor antagonist CP-99994 on the expression of naloxone-precipitated morphine withdrawal symptoms
Effect of intrathecal pretreatment with the neurokinin receptor antagonist CP-99994 on the expression of naloxone-precipitated morphine withdrawal symptoms
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DOI：
10.1016/s0361-9230(97)00013-0
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发表时间：
1997-01-01
影响因子：
3.8
通讯作者：
Shuster, LC
中科院分区：
文献类型：
--
作者：
Buccafusco, JJ;Shuster, LC
在鞘内注射生理盐水（溶剂）预处理的吗啡依赖大鼠中，动脉内注射0.5mg/kg纳洛酮立即引起血压升高，大多数大鼠在注射纳洛酮后立即心率增加;然而，这些反应是短暂的，注射后持续时间不超过约4分钟，纳洛酮引起的行为变化主要表现为在纳洛酮给药后的前10分钟内强烈表达的身体颤抖和逃跑尝试。鞘内注射100 nmol的神经激肽-1受体拮抗剂CP-99994的吗啡依赖大鼠的预处理显着抑制的幅度和缩短的压力反应纳洛酮的持续时间。CP-99994并不减少相关戒断行为的表达，P物质显着逆转CP-99994对戒断相关按压反应表达的抑制作用，鞘内注射CP-99994也能剂量依赖性地抑制局部脊髓压迫反应的表达。在吗啡依赖大鼠中（鞘内）注射纳洛酮（60 μ g）而不显著改变戒断相关行为的表达，这些结果表明，脊髓神经激肽-1受体介导的一些吗啡戒断的心血管体征，并建议开发一类新的抗阿片类药物戒断剂的可能性。(C)1997年爱思唯尔科学公司
In morphine-dependent rats pretreated with an intrathecal injection of saline (vehicle), intraarterial injection of 0.5 mg/kg of naloxone produced an immediate increase in blood pressure, Heart rate increased in most rats just after naloxone injection; however, the responses were transient, not lasting more than about 4 min after injection, Naloxone-precipitated behavioral changes were dominated by the appearance of body shakes and escape attempts that were strongly expressed during the first 10 min after naloxone. Pretreatment of morphine-dependent rats with an intrathecal injection of 100 nmol of the neurokinin-1 receptor antagonist CP-99994 significantly inhibited the magnitude and shortened the duration of the presser response to naloxone. CP-99994 did not reduce the expression of the associated withdrawal behaviors, Substance P significantly reversed the inhibitory effects of CP-99994 on the expression of the withdrawal-associated presser response, Intrathecal pretreatment with CP-99994 also produced a dose-dependent inhibition of the expression of the presser response to local spinal (intrathecal) injection of naloxone (60 mu g) in morphine dependent rats without significant alteration of the expression of withdrawal-associated behaviors, These results indicate that spinal neurokinin-1 receptors mediate some of the cardiovascular signs of morphine withdrawal and suggest the possibility of developing a novel class of antiopiate withdrawal agents. (C) 1997 Elsevier Science Inc.