5-HT(2C) receptors localize to dopamine and GABA neurons in the rat mesoaccumbens pathway.
5-HT(2C) receptors localize to dopamine and GABA neurons in the rat mesoaccumbens pathway.
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DOI：
10.1371/journal.pone.0020508
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Cunningham KA
中科院分区：
文献类型：
--
作者：
Bubar MJ;Stutz SJ;Cunningham KA
5-羟色胺5-HT 2C受体（5-HT 2CR）定位于边缘-皮质纹状体回路，其在介导注意、动机、认知和奖赏过程中起着不可或缺的作用。5-HT 2CR通过激活腹侧被盖区（VTA）中的γ-氨基丁酸（GABA）神经元与中脑多巴胺神经传递的调节有关。然而，我们最近证明了多巴胺VTA神经元内的5-HT 2CR的表达，这表明5-HT 2CR对中脑多巴胺输出的直接影响的可能性。在这里，我们采用双标记荧光免疫化学与多巴胺（酪氨酸羟化酶; TH）和GABA（谷氨酸脱羧酶异构体67; GAD-67）和逆行追踪FluoroGold（FG）的合成酶，以揭示是否多巴胺和GABA VTA神经元，具有5-HT 2CR神经支配的延髓核（NAc）。在腹侧被盖区的中间水平与吻侧和尾侧水平中检测到最高数量的FG标记细胞，并且包括TH-和GAD-67免疫反应性细胞的子集，其中>50%还含有5-HT 2CR免疫反应性。因此，我们首次证明了5-HT 2CR共定位在DA和GABA VTA神经元的项目NAc，详细描述了NAc投射GABA VTA神经元的分布，并确定TH和GAD-67在相同的NAc投射VTA神经元的共定位。这些数据表明，5-HT 2CR可能对多巴胺和GABA VTA输出到NAc产生直接影响。此外，一部分投射NAC的腹侧被盖区神经元合成并可能释放多巴胺和GABA的迹象增加了有趣的复杂性的框架的腹侧被盖区和其假设的神经解剖学作用。
The serotonin 5-HT2C receptor (5-HT2CR) is localized to the limbic-corticostriatal circuit, which plays an integral role in mediating attention, motivation, cognition, and reward processes. The 5-HT2CR is linked to modulation of mesoaccumbens dopamine neurotransmission via an activation of γ-aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA). However, we recently demonstrated the expression of the 5-HT2CR within dopamine VTA neurons suggesting the possibility of a direct influence of the 5-HT2CR upon mesoaccumbens dopamine output. Here, we employed double-label fluorescence immunochemistry with the synthetic enzymes for dopamine (tyrosine hydroxylase; TH) and GABA (glutamic acid decarboxylase isoform 67; GAD-67) and retrograde tract tracing with FluoroGold (FG) to uncover whether dopamine and GABA VTA neurons that possess 5-HT2CR innervate the nucleus accumbens (NAc). The highest numbers of FG-labeled cells were detected in the middle versus rostral and caudal levels of the VTA, and included a subset of TH- and GAD-67 immunoreactive cells, of which >50% also contained 5-HT2CR immunoreactivity. Thus, we demonstrate for the first time that the 5-HT2CR colocalizes in DA and GABA VTA neurons which project to the NAc, describe in detail the distribution of NAc-projecting GABA VTA neurons, and identify the colocalization of TH and GAD-67 in the same NAc-projecting VTA neurons. These data suggest that the 5-HT2CR may exert direct influence upon both dopamine and GABA VTA output to the NAc. Further, the indication that a proportion of NAc-projecting VTA neurons synthesize and potentially release both dopamine and GABA adds intriguing complexity to the framework of the VTA and its postulated neuroanatomical roles.
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