Long-term potentiation of excitatory inputs to brain reward areas by nicotine
Long-term potentiation of excitatory inputs to brain reward areas by nicotine
复制标题
DOI：
10.1016/s0896-6273(00)00042-8
复制
发表时间：
2000-08-01
期刊：
影响因子：
16.2
通讯作者：
McGehee, DS
中科院分区：
文献类型：
--
作者：
Mansvelder, HD;McGehee, DS
尼古丁通过激活中脑多巴胺能 (DA) 奖赏中心（包括腹侧被盖区 (VTA)）的烟碱乙酰胆碱受体 (nAChR) 来强化吸烟行为。尽管尼古丁会在体内引起 VTA 的长时间兴奋，但 DA 神经元上的 nAChR 在几秒钟内就会脱敏。在这里，我们发现 VTA 突触前末梢上 nAChR 的激活增强了 DA 神经元的谷氨酸能输入。在释放的谷氨酸可以激活 NMDA 受体的条件下，会诱导兴奋性输入的长时程增强 (LTP)。尼古丁的短期和长期作用都需要激活含有 α7 亚基的突触前 nAChR。这些结果可以解释短暂接触尼古丁引起的大脑奖励区域的长期兴奋。他们还表明，尼古丁通过与学习和记忆相关的机制改变突触功能。
Nicotine reinforces smoking behavior by activating nicotinic acetylcholine receptors (nAChRs) in the mid-brain dopaminergic (DA) reward centers, including the ventral tegmental area (VTA). Although nicotine induces prolonged excitation of the VTA in vivo, the nAChRs on the DA neurons desensitize in seconds. Here, we show that activation of nAChRs on presynaptic terminals in the VTA enhances glutamatergic inputs to DA neurons. Under conditions where the released glutamate can activate NMDA receptors, long-term potentiation (LTP) of the excitatory inputs is induced. Both the short- and the long-term effects of nicotine required activation of presynaptic alpha 7 subunit-containing nAChRs. These results can explain the long-term excitation of brain reward areas induced by a brief nicotine exposure. They also show that nicotine alters synaptic function through mechanisms that are linked to learning and memory.