The role of K-opioid receptor activation in mediating antinociception and addiction  

作　　者：Yu-hua WANG Jian-feng SUN Yi-min TAO Zhi-qiang CHI Jing-gen LIU 

机构地区：[1]School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China [2]State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Acta Pharmacologica Sinica》2010年第9期1065-1070,共6页中国药理学报（英文版）

摘　　要：The K-opioid receptor （KOR）, a member of the opioid receptor family, is widely expressed in the central nervous system and peripheral tissues. Substantial evidence has shown that activation of KOR by agonists and endogenous opioid peptides in vivo may produce a strong analgesic effect that is free from the abuse potential and the adverse side effects of p-opioid receptor （MOR） agonists, such as morphine. In addition, activation of the KOR has also been shown to exert an inverse effect on morphine-induced adverse actions, such as tolerance, reward, and impairment of learning and memory. Therefore, the KOR has received much attention in the effort to develop alternative analgesics to MOR agonists and agents for the treatment of drug addiction. However, KOR agonists also produce several severe undesirable side effects such as dysphoria, water diuresis, salivation, emesis, and sedation in nonhuman primates, which may limit the clinical utility of KOR agonists for pain and drug abuse treatment. This article will review the role of KOR activation in mediating antinociception and addiction. The possible therapeutic application of K-agonists in the treatment of pain and drug addiction is also discussed.The K-opioid receptor （KOR）, a member of the opioid receptor family, is widely expressed in the central nervous system and peripheral tissues. Substantial evidence has shown that activation of KOR by agonists and endogenous opioid peptides in vivo may produce a strong analgesic effect that is free from the abuse potential and the adverse side effects of p-opioid receptor （MOR） agonists, such as morphine. In addition, activation of the KOR has also been shown to exert an inverse effect on morphine-induced adverse actions, such as tolerance, reward, and impairment of learning and memory. Therefore, the KOR has received much attention in the effort to develop alternative analgesics to MOR agonists and agents for the treatment of drug addiction. However, KOR agonists also produce several severe undesirable side effects such as dysphoria, water diuresis, salivation, emesis, and sedation in nonhuman primates, which may limit the clinical utility of KOR agonists for pain and drug abuse treatment. This article will review the role of KOR activation in mediating antinociception and addiction. The possible therapeutic application of K-agonists in the treatment of pain and drug addiction is also discussed.

关 键 词：K-opioid receptor DYNORPHIN DESENSITIZATION ANTINOCICEPTION tolerance ADDICTION drug withdrawal cocaine reward nega-tive mood state 

分 类 号：Q432[生物学—生理学] S859.791[农业科学—临床兽医学]