U50,488, A KAPPA-OPIOID RECEPTOR AGONIST, ATTENUATES COCAINE-INDUCED INCREASES IN EXTRACELLULAR DOPAMINE IN THE NUCLEUS-ACCUMBENS OF RATS
U50,488, A KAPPA-OPIOID RECEPTOR AGONIST, ATTENUATES COCAINE-INDUCED INCREASES IN EXTRACELLULAR DOPAMINE IN THE NUCLEUS-ACCUMBENS OF RATS
复制标题
DOI：
10.1016/0304-3940(94)90559-2
复制
发表时间：
1994-11-07
影响因子：
2.5
通讯作者：
GLICK, SD
中科院分区：
文献类型：
--
作者：
MAISONNEUVE, IM;ARCHER, S;GLICK, SD
由于伏隔核细胞外多巴胺水平的增加与成瘾药物的增强作用有关，我们采用体内微透析的方法，在清醒和自由活动的大鼠上研究了选择性kappa阿片受体激动剂U50,488是否会改变可卡因引起的伏隔核细胞外多巴胺水平的增加。可卡因(20 mg/kg ip)使细胞外多巴胺水平增加了10倍。U50,488(10毫克/公斤)单独用来引起多巴胺水平轻微下降的预先处理(事前20分钟)，使可卡因对多巴胺水平的影响减少了50%。激动剂激发前20分钟注射kappa阿片受体拮抗剂Nor-binaltorphimine(10 mg/kg S.C.)可完全逆转这种衰减。Nor-binaltorphimine单独治疗可引起多巴胺水平的短暂升高。这些发现表明，kappa受体的激活减弱了可卡因的作用，因此kappa阿片受体激动剂可能是有用的功能性可卡因拮抗剂。
Because an increase in extracellular levels of dopamine in the nucleus accumbens has been associated with the reinforcing effects of addictive drugs, we investigated whether U50,488, a selective kappa opioid receptor agonist, would alter cocaine-induced increases in extracellular dopamine in the nucleus accumbens using in vivo microdialysis in awake and freely moving rats. Cocaine (20 mg/kg i.p.) produced a 10-fold increase in extracellular dopamine levels. Pretreatment (20 min beforehand) with U50,488 (10 mg/kg i.p.), which alone caused a modest decrease in dopamine levels, produced a 50% decrease in the effect of cocaine on dopamine levels. This attenuation was completely reversed by administration of a kappa opioid receptor antagonist, nor-binaltorphimine (10 mg/kg s.c.), 20 min before the agonist challenge. Treatment with nor-binaltorphimine alone induced a brief increase in dopamine levels. These findings indicate that activation of kappa receptors attenuates cocaine's effects and that kappa opioid receptor agonists may, therefore, be useful as functional cocaine antagonists.