Granular Insular Cortex Inactivation as a Novel Therapeutic Strategy for Nicotine Addiction
Granular Insular Cortex Inactivation as a Novel Therapeutic Strategy for Nicotine Addiction
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DOI：
10.1016/j.biopsych.2010.01.029
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发表时间：
2010-08-01
影响因子：
10.6
通讯作者：
Le Foll, Bernard
中科院分区：
文献类型：
--
作者：
Forget, Benoit;Pushparaj, Abhiram;Le Foll, Bernard
背景资料：尼古丁是烟草烟雾的主要成分，导致成瘾，最近的证据表明，对岛叶皮层（INLARCOST）的损伤会破坏人类吸烟者的烟草成瘾。然而，在尼古丁成瘾的动物模型中，这种结构的失活的效果还有待评估。为了研究这个问题，我们研究了局部注射γ-氨基丁酸激动剂混合物对颗粒细胞可逆性失活的影响。（巴氯芬/蝇蕈醇）对尼古丁自我给药（SA）的影响在固定和渐进的比例和恢复尼古丁引发或尼古丁相关线索诱导的尼古丁寻求大鼠。我们还评估了影响的颗粒状尼古丁灭活的食物SA和复发作为control.Results：灭活的颗粒状尼古丁降低尼古丁SA下固定和渐进的比例，而不影响SA的食物下相同的时间表的强化。这种失活也防止了恢复，灭绝后，尼古丁寻求尼古丁相关的线索或尼古丁引发不修改恢复的food seeking.Conclusions：我们的研究表明，完整的颗粒状的尼古丁是必要的表现出的动机，采取尼古丁和尼古丁寻求复发，但不消耗食物颗粒或复发的食物seeking。事实上，研究能够调节大脑活动的方法（如重复经颅磁刺激或深部脑刺激）对人类烟草成瘾和复发的影响可能是有趣的。
Background: Nicotine is the principal component of tobacco smoke, resulting in addiction, and recent evidence suggests that damage to the insular cortex (insula) disrupts tobacco addiction in human smokers. However, the effect of an inactivation of this structure in an animal model of nicotine addiction has yet to be evaluated.Methods: To study this question, we investigated the effects of reversible inactivation of the granular insula by local injection of a gamma-aminobutyric acid agonists mixture (baclofen/muscimol) on nicotine self-administration (SA) under fixed and progressive ratio and on reinstatement of nicotine seeking induced by nicotine priming or nicotine-associated cues in rats. We also evaluated the effects of granular insula inactivation on food SA and relapse as a control.Results: The inactivation of the granular insula decreased nicotine SA under both fixed and progressive ratios without affecting the SA of food under the same schedules of reinforcement. This inactivation also prevented the reinstatement, after extinction, of nicotine seeking induced by nicotine-associated cues or nicotine priming without modifying the reinstatement of food seeking.Conclusions: Our study indicates that the integrity of the granular insula is necessary for exhibiting motivation to take nicotine and to relapse to nicotine seeking but not for consuming food pellets or to relapse for food seeking. Indeed, it might be interesting to study the effect of methods that are able to modulate the activity of the insula such as repetitive transcranial magnetic stimulation or deep brain stimulation on tobacco addiction and relapse in humans.