STRESS-INDUCED AND ENDOTOXIN-INDUCED INCREASES IN BRAIN TRYPTOPHAN AND SEROTONIN METABOLISM DEPEND ON SYMPATHETIC NERVOUS-SYSTEM ACTIVITY
STRESS-INDUCED AND ENDOTOXIN-INDUCED INCREASES IN BRAIN TRYPTOPHAN AND SEROTONIN METABOLISM DEPEND ON SYMPATHETIC NERVOUS-SYSTEM ACTIVITY
复制标题
DOI：
10.1111/j.1471-4159.1991.tb06359.x
复制
发表时间：
1991-11-01
影响因子：
4.7
通讯作者：
WELCH, J
中科院分区：
文献类型：
--
作者：
DUNN, AJ;WELCH, J
压力治疗和免疫挑战以前已经显示出提高色氨酸的大脑浓度。 自主神经系统在这种神经化学变化的作用进行了研究，使用抑制自主神经效应的药物治疗。 预处理与神经节阻滞剂chlorisondamine没有改变正常增加的儿茶酚胺代谢产物，但防止增加脑色氨酸通常观察后，footshock或限制，除了当footshock期间的持续时间延长到60分钟。footshock和限制相关的增加5-羟基吲哚乙酸（5-HIAA）也防止chlorisondamine。 腹腔注射内毒素或白细胞介素-1（IL-1）引起的脑色氨酸的增加也被氯异吲哚胺预处理所阻止。 β-肾上腺素能拮抗剂普萘洛尔，但不是由α-肾上腺素能拮抗剂酚苄明或毒蕈碱胆碱能拮抗剂阿托品减弱足电击诱导的脑色氨酸和5-HIAA的增加。 因此，自主神经系统似乎参与了脑中色氨酸与压力相关的变化，这种效应是由于该系统的交感神经分支而不是副交感神经分支造成的。 此外，交感神经系统的主要作用是对β-肾上腺素能受体而不是α-肾上腺素能受体发挥作用。 我们的结论是，交感神经系统的激活是负责的压力相关的增加，脑色氨酸，可能是通过使脑色氨酸摄取增加。 内毒素和IL-1也可能通过类似的机制升高脑色氨酸。 脑色氨酸的增加似乎是维持应激动物中5-羟色胺对5-HIAA的催化活性增加所必需的，这可能反映了5-羟色胺释放的增加。
Stressful treatments and immune challenges have been shown previously to elevate brain concentrations of tryptophan. The role of the autonomic nervous system in this neurochemical change was investigated using pharmacological treatments that inhibit autonomic effects. Pretreatment with the ganglionic blocker chlorisondamine did not alter the normal increases in catecholamine metabolites, but prevented the increase in brain tryptophan normally observed after footshock or restraint, except when the duration of the footshock period was extended to 60 min. The footshock-and restraint-related increases in 5-hydroxyindoleacetic acid (5-HIAA) were also prevented by chlorisondamine. The increases in brain tryptophan caused by intraperitoneal injection of endotoxin or interleukin-1 (IL-1) were also prevented by chlorisondamine pretreatment. The footshock-induced increases in brain tryptophan and 5-HIAA were attenuated by the beta-adrenergic antagonist propranolol but not by the alpha-adrenergic antagonist phenoxybenzamine or the muscarinic cholinergic antagonist atropine. Thus the autonomic nervous system appears to be involved in the stress-related changes in brain tryptophan, and this effect is due to the sympathetic rather than the parasympathetic limb of the system. Moreover, the main effect of the sympathetic nervous system is exerted on beta- as opposed to alpha-adrenergic receptors. We conclude that activation of the sympathetic nervous system is responsible for the stress-related increases in brain tryptophan, probably by enabling increased brain tryptophan uptake. Endotoxin and IL-1 also elevate brain tryptophan, presumably by a similar mechanism. The increase in brain tryptophan appears to be necessary to sustain the increased serotonin catabolism to 5-HIAA that occurs in stressed animals, and which may reflect increased serotonin release.