The serotonin 2A receptor agonist 25CN-NBOH increases murine heart rate and neck-arterial blood flow in a temperature-dependent manner
The serotonin 2A receptor agonist 25CN-NBOH increases murine heart rate and neck-arterial blood flow in a temperature-dependent manner
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DOI：
10.1177/0269881120903465
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发表时间：
2020-02-12
影响因子：
4.1
通讯作者：
Knopfel, Thomas
中科院分区：
文献类型：
--
作者：
Buchborn, Tobias;Lyons, Taylor;Knopfel, Thomas
背景：5-羟色胺2A受体是致幻剂的分子靶标，由神经元和血管细胞表达，这两种细胞都可能影响致幻状态下的脑血流动力学特征。目的：为了系统地了解致幻剂的血管活性，我们研究了新一代激动剂N-(2-羟基苄基)-2,5-二甲氧基-4-氰基苯乙胺的作用。血清素 2A 受体选择性 - 对大脑供应的颈部动脉血流的选择性。方法：我们记录了麻醉小鼠的核心体温，并采用基于项圈传感器的无创脉搏血氧测定法来提取局部血液灌注、氧饱和度、心脏和呼吸频率的参数。假设血清素能脉冲和体温调节之间存在重叠，则在生理和升高的垫温度下进行记录。结果：N-(2-羟基苄基)-2,5-二甲氧基-4-氰基苯乙胺（1.5 mg/kg，皮下）显着增加心跳频率，同时颈部动脉血流量略有升高。将动物支撑热垫温度从 37 摄氏度提高到 41 摄氏度，增强了药物对血流的作用，同时抵消了心动过速。此外，N-(2-羟基苄基)-2,5-二甲氧基-4-氰基苯乙胺会促进呼吸过缓，与心动过速一样，呼吸过缓在垫温度升高时会迅速逆转。 N-(2-羟基苄基)-2,5-二甲氧基-4-氰基苯乙胺的呼吸心血管作用和体温调节的相互关系通过该药物在升高的垫温下选择性增加核心体温而得到进一步证实。在任一温度下，动脉氧饱和度均不受 N-(2-羟基苄基)-2,5-二甲氧基-4-氰基苯乙胺的影响。 结论：我们的研究结果表明，选择性 5-羟色胺 2A 受体激活可通过温度调节调节全身心血管功能，并与大脑临近的颈动脉（最有可能是颈动脉）直接相关。由于颈动脉分支是将心血管输出输送到大脑或从大脑输送出去的最后一个关键枢纽，因此我们的结果可能会对与迷幻症相关的大脑血流动力学产生影响。
Background:Serotonin 2A receptors, the molecular target of psychedelics, are expressed by neuronal and vascular cells, both of which might contribute to brain haemodynamic characteristics for the psychedelic state.Aim:Aiming for a systemic understanding of psychedelic vasoactivity, here we investigated the effect of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine - a new-generation agonist with superior serotonin 2A receptor selectivity - on brain-supplying neck-arterial blood flow.Methods:We recorded core body temperature and employed non-invasive, collar-sensor based pulse oximetry in anesthetised mice to extract parameters of local blood perfusion, oxygen saturation, heart and respiration rate. Hypothesising an overlap between serotonergic pulse- and thermoregulation, recordings were done under physiological and elevated pad temperatures.Results:N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (1.5 mg/kg, subcutaneous) significantly increased the frequency of heart beats accompanied by a slight elevation of neck-arterial blood flow. Increasing the animal-supporting heat-pad temperature from 37 degrees C to 41 degrees C enhanced the drug's effect on blood flow while counteracting tachycardia. Additionally, N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine promoted bradypnea, which, like tachycardia, quickly reversed at the elevated pad temperature. The interrelatedness of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine's respiro-cardiovascular effects and thermoregulation was further corroborated by the drug selectively increasing the core body temperature at the elevated pad temperature. Arterial oxygen saturation was not affected by N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine at either temperature.Conclusions:Our findings imply that selective serotonin 2A receptor activation modulates systemic cardiovascular functioning in orchestration with thermoregulation and with immediate relevance to brain-imminent neck (most likely carotid) arteries. As carotid branching is a critical last hub to channel cardiovascular output to or away from the brain, our results might have implications for the brain haemodynamics associated with psychedelia.