Widerlöv E, Kilts C D, Mailman R B, Nemeroff C B, Mc Cown T J, Prange A J, Breese G R
J Pharmacol Exp Ther. 1982 Oct;223(1):1-6.
Neurotensin (NT), an endogenous tridecapeptide, is heterogeneously distributed in the central nervous system. The present study examined the effects of physiologically and behaviorally active doses of NT (1--100 micrograms intracisternally) on dopamine, serotonin and their primary metabolites as well as accumulation of dopa after inhibition of dopa decarboxylase. NT was shown to increase dopa accumulation when compared with saline treatment, suggesting that dopamine synthesis was increased. In accord with this view, NT also caused a dose-dependent increase in homovanillic acid and dihydroxyphenylacetic acid, the major metabolites of dopamine, in several brain areas (striatum, olfactory tubercles, nucleus accumbens, frontal cortex and hypothalamus). Interestingly, the increase in homovanillic acid was greater than that for dihydroxyphenylacetic acid. In striatum, an initial increase in dopamine content after 30 micrograms of NT was followed by an increase and a subsequent decrease of dopamine metabolites. Several other neuropeptides (Met-enkephalin, cholecystokinin-8, thyrotropin releasing hormone, substance P and d-Arg9-NT), at doses equimolar to 30 micrograms of NT, did not affect dopamine metabolites, whereas certain others (beta-endorphin and bombesin) increased their concentration in some brain areas. Except for the highest dose of NT, measures of serotonergic function were not affected by NT or any of the other neuropeptides.
神经降压素（NT）是一种内源性十三肽，在中枢神经系统中呈异质性分布。本研究检测了生理和行为活性剂量的NT（脑池内注射1 - 100微克）对多巴胺、5-羟色胺及其主要代谢产物以及多巴脱羧酶抑制后多巴积累的影响。与生理盐水处理相比，NT可增加多巴积累，提示多巴胺合成增加。与此观点一致的是，NT还在几个脑区（纹状体、嗅结节、伏隔核、额叶皮质和下丘脑）引起多巴胺的主要代谢产物高香草酸和二羟基苯乙酸呈剂量依赖性增加。有趣的是，高香草酸的增加幅度大于二羟基苯乙酸。在纹状体中，注射30微克NT后多巴胺含量最初增加，随后多巴胺代谢产物增加，接着又减少。其他几种神经肽（甲硫氨酸脑啡肽、胆囊收缩素-8、促甲状腺激素释放激素、P物质和d-Arg9-NT），在与30微克NT等摩尔的剂量下，不影响多巴胺代谢产物，而其他一些神经肽（β-内啡肽和蛙皮素）在某些脑区会增加其浓度。除了最高剂量的NT外，NT或任何其他神经肽均不影响5-羟色胺能功能指标。
