Ethanol enhances glutamate transmission by retrograde dopamine signaling in a postsynaptic neuron/synaptic bouton preparation from the ventral tegmental area.
Ethanol enhances glutamate transmission by retrograde dopamine signaling in a postsynaptic neuron/synaptic bouton preparation from the ventral tegmental area.
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DOI：
10.1038/npp.2008.143
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
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有文献证明，体树突释放的多巴胺在中脑多巴胺能神经元的兴奋性和突触传递中是重要的。最近，我们发现，在中脑切片，急性乙醇暴露促进多巴胺能传递到腹侧被盖区（VTA）的多巴胺能神经元。腹侧被盖区是一个大脑区域，它对包括酒精在内的滥用药物的奖励作用至关重要。我们推测，乙醇促进可能是由于增加体树突释放多巴胺，其作用于多巴胺D1受体上的谷氨酸释放轴突逆行，从而导致增加谷氨酸释放到多巴胺能神经元。为了进一步检验这一假设，并检查是否乙醇促进可以发生在单细胞水平，腹侧被盖区神经元新鲜分离大鼠大脑使用无酶的程序。这些分离的神经元保留功能性突触末端，包括释放谷氨酸的那些。从这些新分离的假定多巴胺能神经元记录由谷氨酸α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体介导的自发兴奋性突触后电流（sEPSC）。我们发现，急性应用临床相关浓度的乙醇（10 - 80 mM）显著促进了sEPSC的频率，但不是它们的平均振幅。乙醇促进被模仿的D1激动剂SKF 38393和多巴胺摄取阻滞剂GBR 12935，但被阻止的D1拮抗剂SKF 83566，并耗尽多巴胺商店利血平，以及螯合突触后钙与BAPTA。此外，钠通道阻断剂河豚毒素消除了乙醇诱导的sEPSC的促进作用，但SKF 38393没有。这些结果构成了来自单个分离细胞的第一个证据，表明乙醇促进谷氨酸向腹侧被盖区多巴胺能神经元的传递。此外，我们发现乙醇易化有一个突触后起源和一个突触前位点。此外，乙醇刺激单个多巴胺能神经元能够引起体树突多巴胺的释放，这足以影响单个突触的多巴胺能传递。
It is well documented that somatodendritically released dopamine is important in the excitability and synaptic transmission of midbrain dopaminergic neurons. Recently we showed that in midbrain slices, acute ethanol exposure facilitates glutamatergic transmission onto dopaminergic neurons in the ventral tegmental area (VTA). The VTA is a brain region critical to the rewarding effects of abused drugs, including ethanol. We hypothesized that ethanol facilitation might result from an increase in somatodendritically released dopamine, which acts retrogradely on dopamine D1 receptors on glutamate-releasing axons and consequently leads to an increase in glutamate release onto dopaminergic neurons. To further test this hypothesis and to examine whether ethanol facilitation can occur at the single-cell level, VTA neurons were freshly isolated from rat brains using an enzyme-free procedure. These isolated neurons retain functional synaptic terminals, including those that release glutamate. Spontaneous excitatory postsynaptic currents (sEPSCs) mediated by glutamate α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors were recorded from these freshly isolated putative dopaminergic neurons. We found that acute application of clinically relevant concentrations of ethanol (10−80 mM) significantly facilitated the frequency of sEPSCs but not their mean amplitude. Ethanol facilitation was mimicked by the D1 agonist SKF 38393 and by the dopamine uptake blocker GBR 12935 but was blocked by the D1 antagonist SKF 83566, and by depleting dopamine stores with reserpine, as well as by chelating postsynaptic calcium with BAPTA. Furthermore, the sodium channel blocker tetrodotoxin eliminated the facilitation of sEPSCs induced by ethanol but not by SKF 38393. These results constitute the first evidence from single isolated cells of ethanol facilitation of glutamate transmission to dopaminergic neurons in the VTA. In addition, we show that ethanol facilitation has a postsynaptic origin and a presynaptic locus. Furthermore, ethanol stimulation of a single dopaminergic neuron is capable of eliciting the release of somatodendritic dopamine, which is sufficient to influence glutamatergic transmission at individual synapses.
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影响因子：
2.5
作者：
Hernandez, Adan;Sierra, Arturo;Aceves, Jorge
通讯作者：
Aceves, Jorge
影响因子：
3.3
作者：
Iravani, MM;Muscat, R;Kruk, ZL
通讯作者：
Kruk, ZL
DOI：
10.1097/00000374-199911000-00019
发表时间：
1999-11-01
影响因子：
3.2
作者：
Brodie, MS;Pesold, C;Appel, SB
通讯作者：
Appel, SB
影响因子：
5.3
作者：
Ford, CP;Mark, GP;Williams, JT
通讯作者：
Williams, JT
影响因子：
4.7
作者：
BALMFORTH, AJ;WARBURTON, P;BALL, SG
通讯作者：
BALL, SG