The effect of chronic opioid treatment on the expression of delta opioid receptor and N-methyl-D-aspartate(NMDA) in rat brain

• Main Authors: Chen, Huey-Ling, 陳慧鈴
• Other Authors: Yeh Geng-Chang
• Format: Others
• Language: zh-TW
• Published: 1996
• Online Access: http://ndltd.ncl.edu.tw/handle/57943435110413491383

碩士 === 台北醫學院 === 細胞及分子生物研究所 === 84 === Morphine tolerance is a major unsolved issue in analgesic clinics. Down-regulation of opioid receptor has been proposed as a mechanism underlying the generation of morphine tolerance. Previous report suggested that chronic treatment of [D-Ala2, D- Leu5]enkephalin (DADLE) induced a selective down-regulation of d opioid receptor (DOR) at the regions of cortex, midbrain and striatum in rat brain. This change in the d opioid receptor is paralleled with the development of tolerance to DADLE. In addition, the long-term neuropsychological sequels of children born to morphine-addicted woman has long been recognized in clinics. However, the pathological mechanism is still not comprehensive. Recent evidences indicate that the density of N- methyl-D-aspartate receptor (NMDAR) , a receptor plays an important role in developmental plasticity, in hippocampus and amygdala of rats born to morphine-treated dam rats is significant lower than the naive rats (control group) at P14 of post-natal age. To determine whether the decrease in the d opioid receptor and NMDA receptor is due to a decrease in the transcripts of gene encoding these receptors, we quantify the mRNA encoding NMDA receptors and DOR by oligonucleotides probe directed in situ hybridization. The result indicated no significant differences of DOR-1 mRNA in several brain regions between control and DADLE-treated rats except a transient decrease of DOR-1 mRNA in midbrain after 3-day treatment of DADLE. On the other hand, there was a significant decrease of NMDAR (1A, 2A, 2B) mRNA in several brain regions of rat born to morphine-treated dam rats (morphine group) at P30 of post-natal age as compared to that of control group. On the contrary, there was no significant differences of NMDAR (1A, 2A, 2B) mRNA between morphine group and control group at P14 of post-natal age except a transient decrease of NMDAR-2B mRNA at cortex and thalamus was seen in morphine group. These data indicated the decrease of DOR and NMDAR in DADLE-treated rats or rats born to morphine-treated dam rats is not due to a decrease in transcription of these receptors.