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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Presynaptic CB 1 cannabinoid receptors control frontocortical serotonin and glutamate release - Species differences
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Presynaptic CB 1 cannabinoid receptors control frontocortical serotonin and glutamate release - Species differences

机译：突触前CB 1大麻受体控制额皮质5-羟色胺和谷氨酸的释放-物种差异

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Both the serotonergic and endocannabinoid systems modulate frontocortical glutamate release; thus they are well positioned to participate in the pathogenesis of psychiatric disorders. With the help of fluorescent and confocal microscopy, we localized the CB 1 cannabinoid receptor (CB 1R) in VGLUT1- and 2- (i.e. glutamatergic) and serotonin transporter- (i.e. serotonergic) -positive fibers and nerve terminals in the mouse and rat frontal cortex. CB 1R activation by the synthetic agonists, WIN55212-2 (1 μM) and R-methanandamide (1 μM) inhibited the simultaneously measured evoked Ca 2+-dependent release of [ 14C]glutamate and [ 3H]serotonin from frontocortical nerve terminals of Wistar rats, in a fashion sensitive to the CB 1R antagonists, O-2050 (1 μM) and LY320135 (5 μM). CB 1R agonists also inhibited the evoked release of [ 14C]glutamate in C57BL/6J mice in a reversible fashion upon washout. Interestingly, the evoked release of [ 14C]glutamate and [ 3H]serotonin was significantly greater in the CB 1R knockout CD-1 mice. Furthermore, CB 1R binding experiments revealed similar frontocortical CB 1R density in the rat and the CD-1 mouse. Still, the evoked release of [ 3H]serotonin was modulated by neither CB 1R agonists nor antagonists in wild-type CD-1 or C57BL/6J mice. Altogether, this is the first study to demonstrate functional presynaptic CB 1Rs in frontocortical glutamatergic and serotonergic terminals, revealing species differences.
机译：血清素能系统和内源性大麻素系统均调节额皮质谷氨酸的释放。因此，他们处于参与精神疾病发病机制的有利位置。借助荧光和共聚焦显微镜，我们将CB 1大麻素受体（CB 1R）定位于小鼠和大鼠额叶的VGLUT1和2-（即谷氨酸能）和5-羟色胺转运蛋白（即5-羟色胺能）-阳性纤维和神经末梢。皮层。合成激动剂WIN55212-2（1μM）和R-甲烷酰胺（1μM）对CB 1R的激活抑制了同时测定的Wistar额叶神经末梢[14C]谷氨酸和[3H]血清素的诱发的Ca 2+依赖性释放。以对CB 1R拮抗剂敏感的方式对大鼠O-2050（1μM）和LY320135（5μM）敏感。 CB 1R激动剂在冲洗后也可逆地抑制C57BL / 6J小鼠中[14C]谷氨酸的诱发释放。有趣的是，在CB 1R基因敲除CD-1小鼠中[14C]谷氨酸和[3H]血清素的诱发释放明显更大。此外，CB 1R结合实验显示大鼠和CD-1小鼠的额皮质CB 1R密度相似。但是，在野生型CD-1或C57BL / 6J小鼠中，[3 H]血清素的诱发释放不受CB 1R激动剂和拮抗剂的调节。总而言之，这是第一项在额叶谷氨酸能和5-羟色胺能终端显示功能性突触前CB 1Rs的研究，揭示了物种差异。

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