Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal.
Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal.
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甘氨酰谷氨酰胺抑制尼古丁条件性位置偏好和戒断。
DOI：
10.1016/j.ejphar.2005.11.034
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Millington,WilliamR
中科院分区：
文献类型：
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作者：
Goktalay,Gokhan;Cavun,Sinan;Levendusky,MarkC;Hamilton,JonathanR;Millington,WilliamR
甘氨酰-谷氨酰胺（Gly-Gln）是由β-内啡肽1 -31合成的抑制性二肽。以前，我们发现Gly-Gln抑制吗啡条件性位置偏爱、耐受、依赖和戒断。在这项研究中，我们测试了Gly-Gln的抑制活性是否延伸到其他奖励药物，特别是尼古丁。将大鼠用尼古丁（0.6mg/kg，s.c.）四天，第五天测试。甘氨酰-谷氨酰胺（100 nmol i. c. v.）显著抑制尼古丁位置偏爱的获得和表达。环（Gly-Gln）（100 nmol i.c.v.或25 mg/kg i.p.），环状Gly-Gln衍生物阻断尼古丁位置偏爱表达，但Gly-d-Gln（100 nmol i. c. v.）是无效的。为了研究尼古丁戒断，大鼠接受尼古丁（9 mg/kg/天）给药7天，并用美加明（1 mg/kg，s.c.）诱导条件性位置厌恶。甘氨酰-谷氨酰胺阻断了对美加明的位置厌恶的获得，但不阻断U 50，488，一种κ阿片受体激动剂。因此，甘氨酰谷氨酰胺抑制尼古丁的奖励作用，并减弱尼古丁依赖大鼠的戒断反应。
Glycyl-glutamine (Gly-Gln) is an inhibitory dipeptide synthesized from β-endorphin1–31. Previously, we showed that Gly-Gln inhibits morphine conditioned place preference, tolerance, dependence and withdrawal. In this study, we tested whether Gly-Gln's inhibitory activity extends to other rewarding drugs, specifically nicotine. Rats were conditioned with nicotine (0.6 mg/kg, s.c.) for four days and tested on day five. Glycyl-glutamine (100 nmol i.c.v.) inhibited acquisition and expression of a nicotine place preference significantly. Cyclo(Gly-Gln) (100 nmol i.c.v. or 25 mg/kg i.p.), a cyclic Gly-Gln derivative, blocked expression of nicotine place preference but Gly-d-Gln (100 nmol i.c.v.) was ineffective. To study nicotine withdrawal, rats were treated with nicotine (9 mg/kg/day) for seven days and conditioned place aversion was induced with mecamylamine (1 mg/kg, s.c.). Glycyl-glutamine blocked acquisition of place aversion to mecamylamine but not U50,488, a kappa opioid receptor agonist. Glycyl-glutamine thus inhibits the rewarding effects of nicotine and attenuates withdrawal in nicotine dependent rats.