NMDA受体拮抗剂增强大鼠吗啡镇痛作用中的性别差异。

Sex-related differences in the enhancement of morphine antinociception by NMDA receptor antagonists in rats.

作者信息

Holtman Joseph R, Jing Xin, Wala Elzbieta P

机构信息

Department of Anesthesiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.

出版信息

Pharmacol Biochem Behav. 2003 Sep;76(2):285-93. doi: 10.1016/j.pbb.2003.08.007.

DOI:10.1016/j.pbb.2003.08.007

PMID:14592680

Abstract

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonists dextromethorphan (DEX), ketamine (KET), and MK-801 on morphine (MOR)-induced antinociception has been investigated in male and female rats. DEX (7.5, 15, and 30 mg/kg), KET (0.75, 1.5, and 3 mg/kg), and MK-801 (0.075, 0.15, and 0.3 mg/kg) dose-dependently enhanced MOR-induced (3 mg/kg) analgesia in female rats. DEX and KET enhanced the peak effect, whereas MK-801 increased both magnitude and duration of analgesia. DEX also enhanced MOR-induced analgesia in male rats. However, the interaction was of less magnitude in male compared with female rats. The effects of KET and MK-801 on MOR-induced analgesia were negligible in male rats. A 3-mg/kg dose of MOR given alone produced greater analgesia in male than in female rats, but in the presence of NMDA antagonists, MOR elicited similar analgesic responses in both sexes.

摘要

已在雄性和雌性大鼠中研究了N-甲基-D-天冬氨酸（NMDA）受体拮抗剂右美沙芬（DEX）、氯胺酮（KET）和MK-801对吗啡（MOR）诱导的镇痛作用的影响。DEX（7.5、15和30mg/kg）、KET（0.75、1.5和3mg/kg）和MK-801（0.075、0.15和0.3mg/kg）剂量依赖性地增强了雌性大鼠中MOR（3mg/kg）诱导的镇痛作用。DEX和KET增强了峰值效应，而MK-801增加了镇痛的强度和持续时间。DEX也增强了雄性大鼠中MOR诱导的镇痛作用。然而，与雌性大鼠相比，雄性大鼠中的这种相互作用程度较小。KET和MK-801对雄性大鼠中MOR诱导的镇痛作用可忽略不计。单独给予3mg/kg剂量的MOR在雄性大鼠中产生的镇痛作用比雌性大鼠更强，但在存在NMDA拮抗剂的情况下，MOR在两性中引起相似的镇痛反应。