Zhu Hongbo, Barr Gordon A
Biopsychology Doctoral Program, Department of Psychology, Hunter College, City University of New York, 695 Park Avenue, New York, NY 10021, USA Division of Developmental Psychobiology, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Pain. 2003 Aug;104(3):437-447. doi: 10.1016/S0304-3959(03)00051-4.
N-methyl-D-aspartate (NMDA) receptor antagonists are effective in inhibiting the development of morphine tolerance in adult rats. But NMDA receptors undergo dramatic change during the first few weeks of the postnatal life in the rat, and it is unknown whether NMDA receptor antagonists can inhibit the acquisition of opiate tolerance in the developing organism. Here, we investigated the effects of two NMDA receptor antagonists MK-801 and dextromethorphan on the development of morphine tolerance in 7-, 14-, and 21-day-old rats. NMDA receptor antagonists are not effective in attenuating morphine tolerance in the neonatal rat whereas they were partially effected in the 14-day-old and fully effective in rats as old or older than 21 days of age. These data suggest that there exists a transition age, around the second postnatal week in the rat, for the NMDA receptor to play a role in the development of morphine tolerance.
N-甲基-D-天冬氨酸（NMDA）受体拮抗剂能有效抑制成年大鼠吗啡耐受性的形成。但在大鼠出生后的最初几周内，NMDA受体发生显著变化，尚不清楚NMDA受体拮抗剂能否抑制发育中的生物体对阿片类药物耐受性的获得。在此，我们研究了两种NMDA受体拮抗剂MK-801和右美沙芬对7日龄、14日龄和21日龄大鼠吗啡耐受性形成的影响。NMDA受体拮抗剂对新生大鼠吗啡耐受性的减弱无效，而对14日龄大鼠有部分作用，对21日龄及以上大鼠则完全有效。这些数据表明，在大鼠出生后第二周左右存在一个过渡年龄，此时NMDA受体在吗啡耐受性形成中发挥作用。
