Division of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013-4496, USA.
J Neurosci. 2012 Sep 5;32(36):12366-75. doi: 10.1523/JNEUROSCI.5411-11.2012.
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 (SOs) in firing. Pharmacological or structural mPFC inactivation abolished SOs 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 SOs in mPFC pyramidal neurons. mPFC infusion of a non-α7 nicotinic acetylcholine receptor (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.
尼古丁的全身给药会增加腹侧被盖区（VTA）中多巴胺能（DA）神经元的放电，这被认为是尼古丁奖赏的基础。在这里，我们报告内侧前额叶皮层（mPFC）在尼古丁诱导的 VTA DA 神经元兴奋中起着关键作用。在氯醛麻醉的大鼠中，细胞外单细胞记录显示，VTA DA 神经元对全身给予尼古丁表现出两种类型的放电反应。尼古丁注射后，具有 I 型反应的神经元表现出早期双相抑制和随后的兴奋，而具有 II 型反应的神经元则表现出单相兴奋。具有 I 型反应、而非 II 型反应的神经元在放电中表现出明显的慢波振荡（SOs）。药理学或结构 mPFC 失活消除了 SOs，并阻止了全身给予尼古丁后 I 型反应神经元的兴奋，而不是 II 型反应神经元的兴奋，这表明这些 VTA DA 神经元与 mPFC 功能上相耦合，尼古丁通过 mPFC 部分增加这些神经元的放电率。全身给予尼古丁也增加了 mPFC 锥体神经元的放电率和 SOs。mPFC 内注射非-α7 烟碱型乙酰胆碱受体（nAChR）拮抗剂美加仑胺阻断了全身给予尼古丁对具有 I 型反应的 VTA DA 神经元的兴奋作用，但 mPFC 内给予尼古丁未能兴奋这些神经元。这些结果表明，mPFC 中的 nAChR 激活对于全身给予尼古丁后 VTA 神经元的兴奋是必要的，但不是充分的。最后，全身注射荷包牡丹碱可防止具有 I 型反应的神经元中尼古丁引起的放电改变。我们提出，mPFC 在全身给予尼古丁后兴奋 VTA DA 神经元中起着关键作用。
