Kalivas P W, Nemeroff C B, Prange A J
Neuroscience. 1984 Apr;11(4):919-30. doi: 10.1016/0306-4522(84)90203-3.
Neurotensin is an endogenous neuropeptide with neuronal perikarya or fibers distributed in the vicinity of the mesolimbic dopamine system. This observation, plus behavioral data showing that neurotensin injection into the nucleus accumbens blocks some behavioral effects of amphetamine, indicates that neurotensin may modulate the mesolimbic dopamine system. In this study it was shown that neurotensin given into the nucleus accumbens produces a dose-dependent blockade of locomotion and rearing initiated by dopamine injection into the nucleus accumbens. This effect is not mimicked by inactive neurotensin analogue nor some other endogenous neuropeptides. Since dopamine acts on postsynaptic dopamine receptors in the nucleus accumbens, neurotensin is acting, not on dopamine terminals, but on neurons or neuronal systems which are modulated by the mesolimbic dopamine system. This conclusion is supported by the facts that intra-accumbens injection of neurotensin does not alter accumbens levels of dopamine or its metabolites, nor does it affect the increase in dopamine metabolites produced by injection of neurotensin into the ventral tegmental area. Further, neurotensin was also found to block the dopamine-independent increase in locomotion and rearing produced by the injection of D-Ala2-Met- 5enkephalinamide into the nucleus accumbens. These data indicate that neurotensin acts on neurons in the nucleus accumbens to counteract the motor stimulant effects of dopamine or enkephalin. Therefore, in the nucleus accumbens, neurotensin is not acting to modulate the mesolimbic dopamine system, but rather appears to antagonize behavioral hyperactivity, regardless of the neurochemical initiation.
神经降压素是一种内源性神经肽，其神经元胞体或纤维分布于中脑边缘多巴胺系统附近。这一观察结果，加上行为学数据表明向伏隔核注射神经降压素可阻断苯丙胺的某些行为效应，提示神经降压素可能调节中脑边缘多巴胺系统。本研究表明，向伏隔核注射神经降压素可产生剂量依赖性地阻断由向伏隔核注射多巴胺所引发的运动和竖毛行为。这种效应不能被无活性的神经降压素类似物或其他一些内源性神经肽所模拟。由于多巴胺作用于伏隔核的突触后多巴胺受体，神经降压素并非作用于多巴胺终末，而是作用于受中脑边缘多巴胺系统调节的神经元或神经元系统。向伏隔核注射神经降压素不会改变伏隔核中多巴胺或其代谢产物的水平，也不会影响向腹侧被盖区注射神经降压素所产生的多巴胺代谢产物的增加，这些事实支持了这一结论。此外，还发现神经降压素可阻断向伏隔核注射D-丙氨酸2-甲硫氨酸5-脑啡肽酰胺所产生的与多巴胺无关的运动和竖毛行为增加。这些数据表明，神经降压素作用于伏隔核中的神经元，以抵消多巴胺或脑啡肽的运动刺激效应。因此，在伏隔核中，神经降压素并非调节中脑边缘多巴胺系统，而是似乎拮抗行为多动，无论其神经化学起始因素如何。
