Kest B, Lee C E, Mogil J S, Inturrisi C E
Department of Pharmacology, Cornell University Medical College New York, NY 10021, USA.
Life Sci. 1997;60(9):PL155-9. doi: 10.1016/s0024-3205(96)00704-7.
An antisense oligodeoxynucleotide (ODN) targeting 20 bases of the coding sequence of the cloned delta opioid receptor (DOR-1), a mismatched ODN (different from the antisense ODN at 4 bases) or saline was administered to 3 groups of CD-1 mice implanted with naltrexone pellets (7.5 mg) for 7 days. Morphine supersensitivity (i.e., increased potency as defined by decreased morphine ED50 values) was observed 24 h after pellet removal (day 8) in mice treated with saline or mismatch ODN, but not in antisense ODN treated mice. Antisense ODN alone had no effect on basal nociceptive thresholds or morphine analgesia but reduced the analgesic potency of the delta, opioid agonist [D-Ala2]deltorphin II. These data suggest that the delta2 opioid receptor system participates in the adaptive changes contributing to increased morphine potency following chronic naltrexone treatment.
将靶向克隆的δ阿片受体（DOR-1）编码序列20个碱基的反义寡脱氧核苷酸（ODN）、错配ODN（与反义ODN在4个碱基处不同）或生理盐水分别给予3组植入纳曲酮丸剂（7.5毫克）7天的CD-1小鼠。在取出丸剂后24小时（第8天），用生理盐水或错配ODN处理的小鼠出现吗啡超敏反应（即，如通过降低吗啡ED50值所定义的效力增加），而反义ODN处理的小鼠未出现。单独的反义ODN对基础痛觉阈值或吗啡镇痛无影响，但降低了δ阿片受体激动剂[D-Ala2]强啡肽II的镇痛效力。这些数据表明，δ2阿片受体系统参与了慢性纳曲酮治疗后导致吗啡效力增加的适应性变化。
