Impact of prefrontal cortex in nicotine-induced excitation of ventral tegmental area dopamine neurons in anesthetized rats.
Impact of prefrontal cortex in nicotine-induced excitation of ventral tegmental area dopamine neurons in anesthetized rats.
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DOI：
10.1523/jneurosci.5411-11.2012
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发表时间：
2012-09-05
期刊：
影响因子：
--
通讯作者：
Wu J
中科院分区：
文献类型：
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作者：
Zhang D;Gao M;Xu D;Shi WX;Gutkin BS;Steffensen SC;Lukas RJ;Wu J
尼古丁的全身给药会增加腹侧被盖区（VTA）的多巴胺能（DA）神经元放电，这被认为是尼古丁奖励的基础。在这里，我们报告内侧前额叶皮层 (mPFC) 在尼古丁诱导的 VTA DA 神经元兴奋中发挥着关键作用。在水合氯醛麻醉的大鼠中，细胞外单单位记录显示 VTA DA 神经元对全身尼古丁表现出两种类型的放电反应。注射尼古丁后，具有I型反应的神经元表现出双相早期抑制和后期兴奋，而具有II型反应的神经元表现出单相兴奋。具有 I 型反应但没有 II 型反应的神经元在放电时表现出明显的慢振荡 (SO)。药理学或结构性 mPFC 失活消除了 SO，并阻止了系统性尼古丁诱导的具有 I 型而非 II 型反应的神经元兴奋，表明这些 VTA DA 神经元在功能上与 mPFC 耦合，并且尼古丁部分通过 mPFC 增加了这些神经元的放电率。全身尼古丁还增加了 mPFC 锥体神经元的放电率和 SO。 mPFC 输注非 α7 nAChR 拮抗剂美加明可阻断全身尼古丁对具有 I 型反应的 VTA DA 神经元的兴奋作用，但尼古丁的 mPFC 输注未能兴奋这些神经元。这些结果表明，mPFC 中的 nAChR 激活对于系统性尼古丁诱导的 VTA 神经元兴奋是必要的，但还不够。最后，全身注射荷包牡丹碱可防止尼古丁诱导的具有 I 型反应的神经元的放电改变。我们认为 mPFC 在系统性尼古丁诱导的 VTA DA 神经元兴奋中发挥着关键作用。
Systemic administration of nicotine increases dopaminergic (DA) neuron firing in the ventral tegmental area (VTA), which is thought to underlie nicotine reward. Here, we report that the medial prefrontal cortex (mPFC) plays a critical role in nicotine-induced excitation of VTA DA neurons. In chloral hydrate-anesthetized rats, extracellular single-unit recordings showed that VTA DA neurons exhibited two types of firing responses to systemic nicotine. After nicotine injection, the neurons with type-I response showed a biphasic early inhibition and later excitation, whereas the neurons with type-II response showed a monophasic excitation. The neurons with type-I, but not type-II, response exhibited pronounced slow oscillations (SO) in firing. Pharmacological or structural mPFC inactivation abolished SO and prevented systemic nicotine-induced excitation in the neurons with type-I, but not type-II, response, suggesting that these VTA DA neurons are functionally coupled to the mPFC and nicotine increases firing rate in these neurons in part through the mPFC. Systemic nicotine also increased the firing rate and SO in mPFC pyramidal neurons. mPFC infusion of a non-α7 nAChR antagonist mecamylamine blocked the excitatory effect of systemic nicotine on the VTA DA neurons with type-I response, but mPFC infusion of nicotine failed to excite these neurons. These results suggest that nAChR activation in the mPFC is necessary, but not sufficient, for systemic nicotine-induced excitation of VTA neurons. Finally, systemic injection of bicuculline prevented nicotine-induced firing alterations in the neurons with type-I response. We propose that the mPFC plays a critical role in systemic nicotine-induced excitation of VTA DA neurons.