Jones Kathy L, Zhu Hongbo, Jenab Shirzad, Du Ted, Inturrisi Charles E, Barr Gordon A
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY, USA.
Neuropsychopharmacology. 2002 Mar;26(3):301-10. doi: 10.1016/S0893-133X(01)00347-5.
The present study examined the ability of LY235959, a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, to attenuate behaviors and c-fos mRNA expression associated with acute morphine withdrawal in the infant rat. Rat pups were given a single dose of morphine (10.0 mg/kg, s.c.) or saline. Two hours later, pups were removed from the dam and injected with either LY235959 (10.0 mg/kg, s.c.) or saline. Fifteen minutes later acute morphine withdrawal was precipitated with naltrexone (10.0 mg/kg, s.c.) and behaviors were recorded every 15 s for the next 60 min. Immediately after behavioral testing, brain and spinal cord were assayed for c-fos mRNA analysis by solution hybridization. The intensity of the morphine withdrawal syndrome was reduced in pups pre-treated with LY235959. Withdrawal behaviors such as head moves, moving paws, rolling, and walking were decreased, and vocalizations were completely eliminated in pups pre-treated with LY2359559. Acute morphine withdrawal increased c-fos mRNA expression in the brain and the spinal cord, which was attenuated by pre-treatment of LY235959. Thus, in the 7-day-old rat, as in the adult, NMDA receptors play a role in the behavioral and molecular manifestations of acute morphine withdrawal.
本研究检测了竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂LY235959减轻幼鼠急性吗啡戒断相关行为及c-fos mRNA表达的能力。给幼鼠单次注射吗啡（10.0 mg/kg，皮下注射）或生理盐水。两小时后，将幼鼠从母鼠处取出，再给其注射LY235959（10.0 mg/kg，皮下注射）或生理盐水。15分钟后，用纳曲酮（10.0 mg/kg，皮下注射）诱发急性吗啡戒断，并在接下来的60分钟内每隔15秒记录一次行为。行为测试结束后，立即通过溶液杂交法检测脑和脊髓中的c-fos mRNA。预先用LY235959处理的幼鼠，吗啡戒断综合征的强度降低。预先用LY235959处理的幼鼠，诸如头部移动、爪子活动、翻滚和行走等戒断行为减少，并且叫声完全消失。急性吗啡戒断可增加脑和脊髓中c-fos mRNA的表达，而预先用LY235959处理可使其减弱。因此，在7日龄大鼠中，与成年大鼠一样，NMDA受体在急性吗啡戒断的行为和分子表现中发挥作用。
