Inhibition of morphine tolerance and dependence by LY274614, a competitive NMDA receptor antagonist
- VernacularTitle:NMDA受体拮抗剂LY274614对吗啡耐受性和依赖性的抑制作用
- Author:
Wenxian LI
;
Xiaoming DENG
;
Xiaoqin YAN
- Publication Type:Journal Article
- Keywords:
Morphine dependence;
Drug tolerance;
Receptors,N-methyl-D-aspartate;
Excitatory amino acid antagonists
- From:
Chinese Journal of Anesthesiology
1995;0(02):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY274614 [(?)-6-phosphonomethyl-decahydroisoquinolin-3-carboxylic acid] on the development of morphine tolerance and dependence.Methods Male Spraque-Dawley rats were rendered tolerant and dependent by subcutaneous injection of morphine(15mg/kg body weight) three times a day for 10 consecutive days. LY274614 (2, 4, 6 mg/kg body weight) was also given subcutaneously by subcutaneous injection. Antinociception was measured by tail-flick (TF) test. Tail was exposed to the heat source(a beam of high intensity light). The time from the beginning of exposure to removal of tail from the path of the heat source was taken as latency. The baseline TF latency without medication was 4-5 seconds. A ten-second maximum exposure to the heat source was used to minimize damage to tissue during the multiple measurements. Morphine prolonged TF latency. With the development of tolerance TF latency gradually returned to baseline value. Physical dependence on morphine was assessed by abstinence syndrome precipitated by subcutaneous injecting naloxone 10 mg/kg on the tenth day. According to method of Blasig, the number of jumping/30min after naloxone injection was recorded as an index pf abstinence syndrome. Rats were randomly divided into 8 groups (n=6-8). Each group received morphine 15 mg/kg or normal saline (NS) 1.5 ml/kg+LY274614 (2.0,4.0,6.0 mg/kg) or NS, group 1: morphine+NS; group 2: NS+NS; group 3:morphine+LY274614 (2mg/kg); group 4: NS+LY274614 (2mg/kg); group 5: morphine+LY274614 (4mg/kg); group 6: NS+LY274614 (4mg/kg); group 7: morphine+LY274614 (6mg/kg); group 4: NS+LY274614 (6mg/kg).Results LY274614 itself did not have analgesic action, but if used with morphine, it did inhibit the development of tolerance. In group 5 and 7 the decrease in TF latency was more gradual than that in morphine+saline group. 4 and 6 mg/kg LY274614 reduced the number of jumping/30min following naloxone injection.Conclusions LY274614 can inhibit morphine tolerance and dependence rendered by consecutive subcutaneous morphine injection.
