SUPRASPINAL ANTI-ALLODYNIA AND REWARDING EFFECT OF ENDOMORPHINS IN RATS

• Main Authors: Chen CM, 陳慶明
• Other Authors: Tao PL
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/17581193745293343409

碩士 === 國防醫學院 === 藥理學研究所 === 90 === Two potent endogenous opioid peptides, endomorphin-1 (EM-1) and —2 (EM-2), which are selective m-opioid agonists, have been recently isolated from bovine and human brain. These endomorphins have been shown to produce a potent anti-allodynic effect at spinal level. Endomorphins are considered as endogenous ligands for the m-opioid receptor. A prominent characteristic of m-opioid agonists is their ability to elicit strong rewarding effects. Therefore we further investigated their supraspinal anti-allodynic effects and rewarding effects in the present study. In a neuropathic pain model (sciatic nerve crushing in rats), EM-1 and EM-2 (15 mg, i.c.v.) showed significant effects in the cold-water allodynia test. EM-1 is more potent than EM-2. Naltrexone (15 mg) or naloxonazine (15 mg) completely blocked the effects of both EM-1 and EM-2. In a conditioned place preference test, EM-2 at the dose of 30 mg has been shown to produce positive rewarding effects whereas EM-1 or EM-2 at the dose of 15 mg had no effect. EM-2 (30 mg) also increased the extracellular concentration of (DOPAC + HVA) at nucleus accumbens shell, but not EM-1 (15 mg). The present results suggest that the endomorphin-1 is more potent than endophin-2 in anti-neuropathic pain by supraspinal administration. These anti-allodynia effects of endomorphins are possible via m1-opioid receptors. In the conditioned place preference (CPP) test, EM-1 (15mg) and EM-2 (15 mg) did not show any rewarding effect. However, EM-2 produced a significant rewarding effect at the higher dose of 30 mg (i.c.v.). In summary, EM-1 (15 mg) has good supraspinal anti-allodynic effect through the activation of m1-opioid receptors and may be with less tendency to induce psychological dependence. In contrast, EM-2 may be less effective in anti-allodynia and more likely to produce psychological dependence.