Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.
Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.
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DOI：
10.1371/journal.pone.0028142
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ciccocioppo R
中科院分区：
文献类型：
--
作者：
Cippitelli A;Astarita G;Duranti A;Caprioli G;Ubaldi M;Stopponi S;Kallupi M;Sagratini G;Rodrìguez de Fonseca F;Piomelli D;Ciccocioppo R
有证据表明，内源性大麻素系统可调节尼古丁的成瘾特性。在本研究中，我们假设去除长期植入的透皮尼古丁贴片而导致的自发戒断是由内源性大麻素系统调节的。为期 7 天的尼古丁依赖实验（5.2 毫克/大鼠/天）在 Wistar 大鼠中引发了可靠的尼古丁戒断症状。分别在去除尼古丁贴片后 16 小时和 34 小时观察到躯体戒断症状和情感戒断症状。戒断期间还发生了进一步的行为表现，包括运动活动减少和体重增加增加。自发尼古丁戒断的表达伴随着包括杏仁核、海马体、下丘脑和前额皮质在内的多个大脑结构中内源性大麻素 anandamide (AEA) 水平的波动。相反，2-花生四烯酰-sn-甘油的水平没有显着改变。 URB597（0.1 和 0.3 mg/kg，腹腔注射）对脂肪酸酰胺水解酶（FAAH）（一种负责 AEA 细胞内降解的酶）的药理抑制，通过高架十字迷宫测试和休克探针防御掩埋范式评估，减少了戒断诱发的焦虑，但并没有阻止躯体症状的发生。总之，结果表明，旨在增强内源性大麻素信号传导的药理学策略可能为治疗尼古丁戒断产生的负面情感状态提供治疗优势，这对于维持烟草使用至关重要。
Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.
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DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
11.1
作者：
George, Olivier;Ghozland, Sandy;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
3.6
作者：
Cohen, C;Kodas, E;Griebel, G
通讯作者：
Griebel, G
影响因子：
3.6
作者：
Castañé, A;Berrendero, F;Maldonado, R
通讯作者：
Maldonado, R
影响因子：
2.9
作者：
González, S;Cascio, MG;Ramos, JA
通讯作者：
Ramos, JA
影响因子：
7.6
作者：
Bruijnzeel, Adrie W.;Zislis, George;Gold, Mark S.
通讯作者：
Gold, Mark S.