Nicotine-induced changes in neurotransmitter levels in brain areas associated with cognitive function
Nicotine-induced changes in neurotransmitter levels in brain areas associated with cognitive function
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DOI：
10.1023/b:nere.0000035814.45494.15
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Lajtha, A
中科院分区：
文献类型：
--
作者：
Singer, S;Rossi, S;Lajtha, A
尼古丁是最广泛滥用的药物之一，长期以来一直被证明会影响大脑中涉及成瘾和奖励的区域。然而，最近的研究已经开始探索尼古丁对学习和记忆的积极影响。尼古丁与认知功能区域相互作用的机制相对未知。因此，本文是正在进行的研究的一部分，以评估尼古丁增强认知功能的区域影响。本实验观察了尼古丁对腹侧和背侧海马多巴胺（DA）、5-羟色胺（5-HT）、去甲肾上腺素（NE）及其代谢产物高香草酸（HVA）、二羟苯乙酸（DOPAC）、5-羟吲哚乙酸（5-HIAA）及其前体L-DOPA含量的影响（VH和DH）、前额叶和内侧颞叶皮层（PFC和MTC）以及腹侧被盖区（VTA）的脑组织中进行的微透析。将动物用急性尼古丁（0.5 mg/kg，s.c.）在300分钟实验期的中途。给予再摄取阻断剂地昔帕明（100 μ M）和氟西汀（30 μ M）以增加NE和5-HT的水平，以便检测到它们。总体而言，尼古丁诱导的DA增加被发现在某些领域，这种增加是由地昔帕明和氟西汀增强。两个DA代谢产物，HVA和DOPAC，增加在所有领域在整个实验中，无论有和没有抑制剂，表明快速代谢的释放DA。这些代谢产物的增加大于DA的增加。5-HT增加的DH，MTC，和VTA的氟西汀的存在下，其代谢产物，5-HIAA，增加在氟西汀的存在和不存在。除腹侧被盖区外，地昔帕明和氟西汀组NE水平升高程度相似。总的来说，尼古丁似乎增加了这三种神经递质的释放和周转，其代谢产物显著增加表明了这一点。此外，DA，尤其是HVA和DOPAC，增加尼古丁给药后150分钟; 5-HT和NE的变化持续时间较短。由于气相色谱实验表明，150分钟后大脑中的尼古丁水平下降了75%，这可能表明DA比5-HT或NE更容易受到较低水平的尼古丁的影响。总之，急性尼古丁给药引起DA，5-HT和NE水平的变化，并在DA和5-HT的代谢，在大脑区域参与认知过程。
Nicotine, one of the most widespread drugs of abuse, has long been shown to impact areas of the brain involved in addiction and reward. Recent research, however, has begun to explore the positive effects that nicotine may have on learning and memory. The mechanisms by which nicotine interacts with areas of cognitive function are relatively unknown. Therefore, this paper is part of an ongoing study to evaluate regional effects of nicotine enhancement of cognitive function. Nicotine-induced changes in the levels of three neurotransmitters, dopamine (DA), serotonin (5-HT), norepinepherine ( NE), their metabolites, homovanillic acid (HVA), dihydroxyphenylacetic acid ( DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and their precursor, L-DOPA, were evaluated in the ventral and dorsal hippocampus (VH and DH), prefrontal and medial temporal cortex (PFC and MTC), and the ventral tegmental area (VTA) using in vivo microdialysis in awake, freely moving, male Sprague-Dawley rats. The animals were treated with acute nicotine (0.5 mg/kg, s.c.) halfway through the 300-min experimental period. The reuptake blockers, desipramine (100 muM) and fluoxetine (30 muM), were given to increase the levels of NE and 5-HT so that they could be detected. Overall, a nicotine-induced DA increase was found in some areas, and this increase was potentiated by desipramine and fluoxetine. The two DA metabolites, HVA and DOPAC, increased in all the areas throughout the experiments, both with and without the inhibitors, indicating a rapid metabolism of the released DA. The increase in these metabolites was greater than the increase in DA. 5-HT was increased in the DH, MTC, and VTA in the presence of fluoxetine; its metabolite, 5-HIAA, was increased in the presence and absence of fluoxetine. Except in the VTA, NE levels increased to a similar extent with desipramine and fluoxetine. Overall, nicotine appeared to increase the release and turnover of these three neurotransmitters, which was indicated by significant increases in their metabolites. Furthermore, DA, and especially HVA and DOPAC, increased for the 150 min following nicotine administration; 5-HT and NE changes were shorter in duration. As gas chromatography experiments showed that nicotine levels in the brain decreased by 75% after 150 min, this may indicate that DA is more susceptible to lower levels of nicotine than 5-HT or NE. In conclusion, acute nicotine administration caused alterations in the levels of DA, 5-HT, and NE, and in the metabolism of DA and 5-HT, in brain areas that are involved in cognitive processes.