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Neurochemical impact of the 5-HT2C receptor agonist WAY-163909 on monoamine tissue content in the rat brain.
Neurochemistry international ( IF 4.2 ) Pub Date : 2019-01-24 , DOI: 10.1016/j.neuint.2019.01.019
Abdeslam Chagraoui 1 , Sara Whitestone 2 , Lynn Baassiri 2 , Julien Manem 2 , Giuseppe Di Giovanni 3 , Philippe De Deurwaerdère 2
Affiliation  

Serotonin2C receptor (5-HT2C) agonists are promising drugs for the treatment of neuropsychiatric diseases. However, their effect is not completely understood in part because they possibly affect several neurobiological networks simultaneously. We studied the effect of the 5-HT2C receptor agonist WAY-163909 (0.3 and 3 mg/kg; i.p.) on the tissue concentration of dopamine (DA), 5-HT and noradrenaline (NA) in 29 rat brain regions related to motor, cognitive, mood and vegetative networks. We found that WAY-163909, without altering the tissue concentration of NA, increased 5-HT concentrations in the medial orbitofrontal cortex and the motor cortex M2 at 3 mg/kg and decreased it in the dorsolateral orbitofrontal cortex at 0.3 mg/kg. WAY-163909 enhanced DA concentrations in the central nucleus of the amygdala at 0.3 mg/kg and reduced it in the dorsal hypothalamus at 3 mg/kg. Using correlative analysis of the tissue content of monoamines, WAY-163909 dramatically changed the profile and the pattern of the correlations within and between monoaminergic systems without drastically changing the total number of these correlations. The profile of these changes in correlations was dose-dependent as it was very different between the two doses within and among monoaminergic systems. In conclusion, the data indicated that the 5-HT2C receptor agonist WAY-163909 quantitatively alters monoamine content in very few regions but promotes multiple changes of monoaminergic connectivity in the brain.

中文翻译:

5-HT2C受体激动剂WAY-163909对大鼠脑中单胺组织含量的神经化学影响。

血清素2C受体(5-HT2C)激动剂是用于治疗神经精神疾病的有前途的药物。但是,由于它们可能同时影响多个神经生物学网络,因此其作用尚未完全被部分理解。我们研究了5-HT2C受体激动剂WAY-163909(0.3和3 mg / kg; ip)对29只与运动相关的大鼠脑区域中多巴胺(DA),5-HT和去甲肾上腺素(NA)组织浓度的影响,认知,情绪和植物网络。我们发现,WAY-163909在不改变NA组织浓度的情况下,以3 mg / kg的浓度增加眼眶前额皮质和运动皮层M2中的5-HT浓度,并以0.3 mg / kg减少眼眶额叶皮质中的5-HT浓度。WAY-163909增强了杏仁核中央核在0时的DA浓度。3 mg / kg,并以3 mg / kg降低其在下丘脑背侧。使用单胺组织含量的相关分析,WAY-163909大大改变了单胺能系统内和之间的相关性概况和模式,而没有大幅度改变这些相关性的总数。这些相关性变化的曲线是剂量依赖性的,因为在单胺能系统内和之间的两种剂量之间存在很大差异。总之,数据表明5-HT2C受体激动剂WAY-163909在极少数区域定量改变了单胺含量,但促进了大脑中单胺能连接性的多种变化。WAY-163909极大地改变了单胺能系统内和之间的相关性概况和模式,而没有大幅度改变这些相关性的总数。这些相关性变化的曲线是剂量依赖性的,因为在单胺能系统内和之间的两种剂量之间存在很大差异。总之,数据表明5-HT2C受体激动剂WAY-163909在极少数区域定量改变了单胺含量,但促进了大脑中单胺能连接性的多种变化。WAY-163909极大地改变了单胺能系统内和之间的相关性概况和模式,而没有大幅度改变这些相关性的总数。这些相关性变化的曲线是剂量依赖性的,因为在单胺能系统内和之间的两种剂量之间存在很大差异。总之,数据表明5-HT2C受体激动剂WAY-163909在极少数区域定量改变了单胺含量,但促进了大脑中单胺能连接性的多种变化。
更新日期:2019-01-24
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