Roles of pedunculopontine tegmental cholinergic receptors in brain stimulation reward in the rat
Roles of pedunculopontine tegmental cholinergic receptors in brain stimulation reward in the rat
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DOI：
10.1007/s00213-005-0252-8
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发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
Nakahara, D
中科院分区：
文献类型：
--
作者：
Chen, J;Nakamura, M;Nakahara, D
基本原理：脑干脚桥被盖核（PPTg）被认为通过腹侧被盖区（VTA）的胆碱能激活来介导下丘脑自我刺激奖赏。然而，迄今为止，几乎没有直接证据支持这一假设。目的：进一步研究PPTg在下丘脑自我刺激奖赏中的作用。方法：采用体内微透析技术，检测大鼠下丘脑外侧（LH）自我刺激过程中PPTg和VTA中细胞外乙酰胆碱（ACh）的水平。采用速率-频率曲线平移程序评价微量注射到PPTg中的非选择性毒蕈碱拮抗剂东莨菪碱（1个，相当于100μg/μl）和烟碱拮抗剂美加明（5个，相当于100μg/μl）对LH自我刺激的奖励功效的影响。随后，将药物注射到PPTg中，并测量VTA中的细胞外ACh。结果：LH 自我刺激在 PPTg 和 VTA 中产生同时的 ACh 释放。 PPTg内注射东莨菪碱（100μg/μl）显着降低了LH自我刺激奖励的频率阈值，但烟碱拮抗剂美加明没有改变阈值。然而，注射到 PPTg 中的美加明（10、25 μg/μl）会显着降低尼古丁增强的 LH 自我刺激奖励。 PPTg内东莨菪碱（10、100μg/μl）可显着增加VTA中的细胞外ACh，但美加明则不会。结论：结果证实 PPTg 通过调节 VTA 的胆碱能活性在大脑刺激奖励中发挥重要作用。 PPTg 毒蕈碱受体有助于通过自我刺激对奖赏效应进行抑制性调节，而烟碱受体似乎更多地参与尼古丁对大脑刺激奖赏的增强。
Rationale: The brainstem pedunculopontine tegmental nucleus (PPTg) is proposed to mediate hypothalamic self-stimulation reward via cholinergic activation of the ventral tegmental area (VTA). However, to date there is little direct evidence to support this hypothesis. Objectives: To further study the role of PPTg in hypothalamic self-stimulation reward. Methods: By using in vivo microdialysis, the levels of extracellular acetylcholine (ACh) in the PPTg and VTA were detected during lateral hypothalamic (LH) self-stimulation in rats. Rate-frequency curve shift procedure was used to evaluate the effects of nonselective muscarinic antagonist scopolamine (1 similar to 100 mu g/mu l) and nicotinic antagonist mecamylamine (5 similar to 100 mu g/mu l) microinjected into the PPTg on the rewarding efficacy of LH self-stimulation. Subsequently, the drugs were injected into the PPTg, and the extracellular ACh in the VTA was measured. Results: LH self-stimulation produced a concurrent ACh release in the PPTg and VTA. Intra-PPTg injection of scopolamine (100 mu g/mu l) significantly reduced the frequency threshold for LH self-stimulation reward, but nicotinic antagonist mecamylamine did not shift the threshold. However, mecamylamine (10, 25 mu g/mu l) injected into the PPTg robustly diminished the nicotine-potentiated LH self-stimulation reward. The extracellular ACh in the VTA was dramatically increased by intra-PPTg scopolamine (10, 100 mu g/mu l), but not by mecamylamine. Conclusions: Results confirm that PPTg plays an important role in brain stimulation reward by modulating the cholinergic activity of the VTA. The PPTg muscarinic receptors contribute to an inhibitory modulation of reward effects by self-stimulation, whereas nicotinic receptors seem to be more involved in nicotine potentiation of brain stimulation reward.