Activation of GABAergic neurons in the interpeduncular nucleus triggers physical nicotine withdrawal symptoms.
Activation of GABAergic neurons in the interpeduncular nucleus triggers physical nicotine withdrawal symptoms.
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DOI：
10.1016/j.cub.2013.09.041
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发表时间：
2013-12-02
期刊：
影响因子：
9.2
通讯作者：
Tapper, Andrew R.
中科院分区：
文献类型：
--
作者：
Zhao-Shea, Rubing;Liu, Liwang;Pang, Xueyan;Gardner, Paul D.;Tapper, Andrew R.
长期暴露于尼古丁会增强吸烟者的身体依赖性，但戒断症状的机制和神经解剖学基础尚不清楚。与人类一样，啮齿类动物在慢性尼古丁戒断后也会出现身体戒断症状，其特征是抓挠、头部痉挛和身体抖动增加。在这里，我们表明，物理尼古丁戒断症状的诱导激活脚间核（IPN）内的GABA能神经元。通过光刺激视紫红质通道光激活IPN GABA能神经元引起尼古丁未处理和长期尼古丁暴露小鼠的身体戒断症状。在尼古丁戒断过程中，通过IPN选择性输注NMDA受体拮抗剂或通过阻断内侧缰的IPN神经传递来抑制GABA能神经元的兴奋性，从而减少IPN神经元的激活并减轻戒断症状。在慢性尼古丁暴露过程中，含有β4亚基的烟碱型乙酰胆碱受体在IPN背侧区聚集的生长抑素中间神经元中上调。阻断这些受体诱导戒断症状更显着尼古丁依赖的尼古丁相比，尼古丁初治小鼠和激活非生长抑素神经元的IPN。总之，我们的数据表明，在尼古丁戒断期间降低IPN GABA能神经元兴奋性的治疗策略，例如，通过激活生长抑素中间神经元上的烟碱受体，可能有利于缓解戒断症状和促进戒烟。
Chronic exposure to nicotine elicits physical dependence in smokers, yet the mechanism and neuroanatomical bases for withdrawal symptoms are unclear. As in humans, rodents undergo physical withdrawal symptoms after cessation from chronic nicotine characterized by increased scratching, head nods, and body shakes. Here we show that induction of physical nicotine withdrawal symptoms activates GABAergic neurons within the interpeduncular nucleus (IPN). Optical activation of IPN GABAergic neurons via light stimulation of channel rhodopsin elicited physical withdrawal symptoms in both nicotine-naïve and chronic nicotine-exposed mice. Dampening excitability of GABAergic neurons during nicotine withdrawal through IPN-selective infusion of an NMDA receptor antagonist or through blocking IPN neurotransmission from the medial habenula reduced IPN neuronal activation and alleviated withdrawal symptoms. During chronic nicotine exposure, nicotinic acetylcholine receptors containing the β4 subunit were upregulated in somatostatin interneurons clustered in the dorsal region of the IPN. Blockade of these receptors induced withdrawal signs more dramatically in nicotine-dependent compared to nicotine-naïve mice and activated non-somatostatin neurons in the IPN. Together, our data indicate that therapeutic strategies to reduce IPN GABAergic neuron excitability during nicotine withdrawal, for example, by activating nicotinic receptors on somatostatin interneurons, may be beneficial for alleviating withdrawal symptoms and facilitating smoking cessation.
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影响因子：
13.9
作者：
Fenno L;Yizhar O;Deisseroth K
通讯作者：
Deisseroth K
DOI：
10.1523/jneurosci.2601-10.2010
发表时间：
2010-07-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hendrickson LM;Zhao-Shea R;Pang X;Gardner PD;Tapper AR
通讯作者：
Tapper AR
DOI：
10.1124/jpet.107.132977
发表时间：
2008-04-01
影响因子：
3.5
作者：
Jackson, K. J.;Martin, B. R.;Damaj, M. I.
通讯作者：
Damaj, M. I.
影响因子：
34.7
作者：
Hikosaka, Okihide
通讯作者：
Hikosaka, Okihide
影响因子：
3.8
作者：
HAMILL, GS;JACOBOWITZ, DM
通讯作者：
JACOBOWITZ, DM