Trigo Jose M, Le Foll Bernard
Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), 33 Russell Street, Toronto, ON, M5S 2S1, Canada.
Addictions Division, CAMH, Toronto, ON, Canada.
Psychopharmacology (Berl). 2016 May;233(10):1815-22. doi: 10.1007/s00213-015-4117-5. Epub 2015 Oct 22.
Tobacco smoking is still a major population health issue. The endocannabinoid system has been shown to control drug-seeking behaviors. There are two main endocannabinoids: anandamide degraded by fatty acid amide hydrolase (FAAH) and 2-arachidonoylglycerol (2-AG) degraded by monoacylglycerol lipase (MAGL).
The role of MAGL has only been explored recently, and so far, no study have been performed to evaluate the effects of MAGL inhibitor on nicotine reinforcing properties and cue-induced reinstatement of nicotine seeking.
Here, we investigated the effects of the MAGL inhibitor JZL184 on nicotine self-administration under fixed and progressive-ratio schedules of reinforcement and on cue-induced reinstatement of nicotine seeking in mice. We also evaluated the effects of JZL184 on food self-administration for possible non-specific effects.
JZL184 (0, 8, and 16 mg/kg) did not affect food taking, nicotine taking, or motivation for nicotine. MAGL inhibition by JZL184 (16 mg/kg) increased reinstatement of previously extinguished nicotine seeking induced by presentation of nicotine-associated cues, but did not produce reinstatement on its own.
This study implicates involvement of 2-AG in nicotine-seeking behaviors.
吸烟仍是一个主要的人群健康问题。内源性大麻素系统已被证明可控制觅药行为。有两种主要的内源性大麻素：由脂肪酸酰胺水解酶（FAAH）降解的花生四烯乙醇胺和由单酰甘油脂肪酶（MAGL）降解的2-花生四烯酸甘油（2-AG）。
MAGL的作用直到最近才被研究，并且迄今为止，尚未有研究评估MAGL抑制剂对尼古丁强化特性以及线索诱导的尼古丁觅药恢复的影响。
在此，我们研究了MAGL抑制剂JZL184在固定和累进比率强化程序下对小鼠尼古丁自我给药以及对线索诱导的尼古丁觅药恢复的影响。我们还评估了JZL184对食物自我给药的影响，以确定是否存在非特异性效应。
JZL184（0、8和16mg/kg）不影响食物摄取、尼古丁摄取或对尼古丁的动机。JZL184（16mg/kg）对MAGL的抑制增加了由呈现尼古丁相关线索诱导的先前消退的尼古丁觅药恢复，但自身不会产生觅药恢复。
本研究表明2-AG参与了尼古丁觅药行为。
Zotero 插件