A novel neurotensin analog blocks cocaine- and D-amphetamine-induced hyperactivity
A novel neurotensin analog blocks cocaine- and D-amphetamine-induced hyperactivity
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DOI：
10.1016/s0014-2999(01)01197-9
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发表时间：
2001-08-24
影响因子：
5
通讯作者：
Richelson, E
中科院分区：
文献类型：
--
作者：
Boules, M;Warrington, L;Richelson, E
神经降压素是一种十三肽，与多巴胺能系统具有选择性的解剖和神经化学相互作用。由于多巴胺能神经传递是精神刺激剂许多行为特性的基础，而且神经降压素参与调节多巴胺能神经递质系统，我们测试了我们的新的神经降压素类似物NT69L(N-甲基-精氨酸(8)，L-赖斯(9)，L-新色氨酸(11)，叔亮氨酸(12))神经降压素-(8-13)对可卡因和D-苯丙胺引起的多动的影响。在此之前，我们发现NT69L可以降低体温，阻断阿朴吗啡诱导的爬升，以及氟哌啶醇诱导的惊厥。在这项研究中，NT69L阻断了可卡因和D-苯丙胺引起的兴奋，分别以三个不同的剂量给药，当这种多肽被注射到腹膜后。这些结果为神经降压素系统参与精神刺激剂的一些行为特性提供了进一步的证据，并表明NT69L可能在滥用这类化合物的患者中找到临床应用。(C)2001 Elsevier Science B.V.保留所有权利。
Neurotensin is a tridecapeptide that exhibits selective anatomic and neurochemical interactions with dopaminergic systems. Since dopaminergic neurotransmission underlies many of the behavioral properties of psychostimulants, and since neurotensin has been implicated in modulating dopaminergic neurotransmitter systems, we tested the effect of our novel neurotensin analog, NT69L (N-methyl-Arg(8),L-Lys(9),L-neo-Trp(11),tert-Leu(12)]neurotensin-(8-13)), on hyperactivity caused by cocaine and D-amphetamine. Previously, we showed that NT69L reduces body temperature, blocks apomorphine-induced climbing, and haloperidol-induced catalepsy. In this study, NT69L blocked the hyperactivity induced by both cocaine and D-amphetamine administered at three different doses each, when this peptide was injected intraperitoneally. These results provide further evidence for the involvement of the neurotensin system in some of the behavioral properties of psychostimulants and suggest that NT69L may find clinical application in patients who abuse this class of compounds. (C) 2001 Elsevier Science B.V. All rights reserved.