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首页> 外文期刊>Life sciences >Neurochemical effects of the endocannabinoid uptake inhibitor UCM707 in various rat brain regions.
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Neurochemical effects of the endocannabinoid uptake inhibitor UCM707 in various rat brain regions.

机译：内源性大麻素摄取抑制剂UCM707在各种大鼠脑区域的神经化学作用。

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摘要

To date, UCM707, (5Z,8Z,11Z,14Z)-N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide, has the highest potency and selectivity in vitro and in vivo as inhibitor of the endocannabinoid uptake. Its biochemical, pharmacological and therapeutic properties have been intensely studied recently, but the information on its capability to modify neurotransmitter activity, which obviously underlies the above properties, is still limited. In the present study, we conducted a time-course experiment in rats aimed at examining the neurochemical effects of UCM707 in several brain regions following a subchronic administration (5 injections during 2.5 days) of this inhibitor in a dose of 5 mg/kg weight. In the hypothalamus, the administration of UCM707 did not modify GABA contents but reduced norepinephrine levels at 5 h after administration, followed by an increase at 12 h. Similar trends were observed for dopamine, whereas serotonin content remained elevated at 1 and, in particular, 5 and 12 h after administration. In the case of the basal ganglia, UCM707 reduced GABA content in the substantia nigra but only at longer (5 or 12 h) times after administration. There were no changes in serotonin content, but a marked reduction in its metabolite 5HIAA was recorded in the substantia nigra. The same pattern was found for dopamine, contents of which were not altered by UCM707 in the caudate-putamen, but its major metabolite DOPAC exhibited a marked decrease at 5 h. In the cerebellum, UCM707 reduced GABA, serotonin and norepinephrine content, but only the reduction found for norepinephrine at 5 h reached statistical significance. The administration of UCM707 did not modify the contents of these neurotransmitters in the hippocampus and the frontal cortex. Lastly, in the case of limbic structures, the administration of UCM707 markedly reduced dopamine content in the nucleus accumbens at 5 h, whereas GABA content remained unchanged in this structure and also in the ventral-tegmental area and the amygdala. By contrast, norepinephrine and serotonin content increased at 5 h in the nucleus accumbens, but not in the other two limbic structures. In summary, UCM707 administered subchronically modified the contents of serotonin, GABA, dopamine and/or norepinephrine with a pattern strongly different in each brain region. So, changes in GABA transmission (decrease) were restricted to the substantia nigra, but did not appear in other regions, whereas dopamine transmission was also altered in the caudate-putamen and the nucleus accumbens. By contrast, norepinephrine and serotonin were altered by UCM707 in the hypothalamus, cerebellum (only norepinephrine), and nucleus accumbens, exhibiting biphasic effects in some cases.
机译：迄今为止，UCM707（5Z，8Z，11Z，14Z）-N-（3-呋喃甲基）二十碳五，8,11,14-四烯酰胺作为内源性大麻素抑制剂在体外和体内具有最高的效能和选择性摄取。最近已经对其生化，药理和治疗性质进行了深入研究，但是关于其修饰神经递质活性的能力（显然是上述性质的基础）的信息仍然有限。在本研究中，我们在大鼠中进行了一个时程实验，旨在检查在以5 mg / kg体重的亚慢性给药（2.5天内注射5次）后，UCM707在几个脑区的神经化学作用。在下丘脑中，施用UCM707不会改变GABA含量，但会在施用后5 h降低去甲肾上腺素水平，随后在12 h增加。对于多巴胺，观察到相似的趋势，而5-羟色胺含量在给药后1小时，尤其是5和12小时保持升高。对于基底神经节，UCM707降低了黑质中的GABA含量，但仅在给药后更长的时间（5或12小时）内。 5-羟色胺含量没有变化，但是黑质中记录到其代谢产物5HIAA明显减少。对于多巴胺，发现了相同的模式，其含量在尾状-丘脑中未被UCM707改变，但其主要代谢产物DOPAC在5 h时表现出明显的下降。在小脑中，UCM707降低了GABA，5-羟色胺和去甲肾上腺素的含量，但只有5h时去甲肾上腺素的减少才具有统计学意义。 UCM707的使用未改变海马和额叶皮层中这些神经递质的含量。最后，在边缘结构的情况下，UCM707的施用在5 h时伏隔核中的多巴胺含量显着降低，而在该结构以及腹侧被盖区和杏仁核中，GABA含量保持不变。相比之下，伏隔核中去甲肾上腺素和5-羟色胺含量在5 h时增加，而在其他两个边缘结构中则没有。综上所述，UCM707所管理的亚血清素，GABA，多巴胺和/或去甲肾上腺素的含量被亚慢性修饰，其模式在每个大脑区域都有很大不同。因此，GABA传递（减少）的变化仅限于黑质，而在其他区域则没有出现，而多巴胺的传递在尾状-壳状核和伏隔核中也发生了变化。相比之下，UCM707在下丘脑，小脑（仅去甲肾上腺素）和伏隔核中改变了去甲肾上腺素和5-羟色胺，在某些情况下表现出双相作用。

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