Mohanty S, Steinbusch H W, Ganguly D K, Mohanakumar K P
Division of Pharmacology and Experimental Therapeutics, Indian Institute of Chemical Biology, Calcutta.
J Chem Neuroanat. 1998 Jun;14(3-4):141-9. doi: 10.1016/s0891-0618(98)00028-3.
The effects of intracerebroventricular injections of serotonin (5-HT) antibodies were studied for changes in 5-HT, dopamine (DA), their metabolites and norepinephrine (NE) as well as 5-HT mediated behavior in adult mice. While nociceptive thresholds (tail-flick latency) were inhibited in antibody treated animals, tremor response to 5-methoxy-N,N-dimethyl tryptamine administration was increased. 5-HT and DA in the nucleus raphe dorsalis (NRD), substantia nigra (SN), nucleus caudatus putamen (NCP) and in the substantia grisea centralis, and NE in the former two nuclei were significantly decreased in these animals. 5-Hydroxyindoleacetic acid was unaffected in all nuclei except NRD, where it was inhibited. Homovanillic acid and 3,4-dihydroxyphenylacetic acid were inhibited in all nuclei except in NCP. The brunt of insult was more evident in NRD and SN where all neurotransmitters were inhibited for a longer period. 5-HT turnover was increased in all the nuclei, however only SN showed increased DA turnover. It may be assumed that the observed neurochemical and behavioral changes were the consequence of the antibodies binding to 5-HT, which in turn influenced the anatomically and functionally connected neurotransmitters. While the study contributes to the existing understanding of central neurotransmitter control on behavior, it fails to delineate the underlying mechanism. The possibility of developing a useful, drug-free 5-HT deficient animal model for studying clinical disorders, as well as for solving some of the basic questions related to the physiological functions of 5-HT in adult animals are envisaged from the study.
研究了向成年小鼠脑室内注射血清素(5-羟色胺,5-HT)抗体后,5-HT、多巴胺(DA)、它们的代谢产物以及去甲肾上腺素(NE)的变化,以及5-HT介导的行为。虽然抗体处理的动物的伤害性感受阈值(甩尾潜伏期)受到抑制,但对5-甲氧基-N,N-二甲基色胺给药的震颤反应增强。这些动物中,背侧中缝核(NRD)、黑质(SN)、尾状核壳核(NCP)和中央灰质中的5-HT和DA,以及前两个核中的NE显著减少。除NRD中5-羟吲哚乙酸受到抑制外,所有核中的5-羟吲哚乙酸均未受影响。除NCP外,所有核中的高香草酸和3,4-二羟基苯乙酸均受到抑制。损伤的冲击在NRD和SN中更为明显,其中所有神经递质被抑制的时间更长。所有核中的5-HT周转率均增加,但只有SN中的DA周转率增加。可以推测,观察到的神经化学和行为变化是抗体与5-HT结合的结果,这反过来又影响了解剖学和功能上相连的神经递质。虽然该研究有助于现有对中枢神经递质对行为控制的理解,但未能阐明其潜在机制。该研究设想了开发一种有用的、无药物的5-HT缺乏动物模型的可能性,用于研究临床疾病,以及解决一些与成年动物中5-HT生理功能相关的基本问题。