Willis G L, Smith G C
Brain Res. 1985 Jun;356(2):109-32. doi: 10.1016/0165-0173(85)90009-8.
When nigro-striatal and meso-cortical neurons degenerate there is a loss of dopamine in the terminal fields and an accumulation of amines in the axons of these systems as they traverse the hypothalamus through the medial forebrain bundle. Traditional lines of thought have attributed the occurrence of motor and consummatory deficits which occur after dopamine neuron degeneration to the loss of functional dopamine neurotransmitter in the terminal fields. However, we have hypothesized that hypothalamic amine accumulation represents an area of brain tissue where processes such as neurotransmitter release, ephaptic transmission or local axon swelling may be affecting adjacent neurons and may thereby participate in the production of behavioural deficits. There is a considerable amount of evidence from studies on both peripheral and central catecholamine-containing neurons indicating that when their axons degenerate a release of functional neurotransmitter can occur. Information from neuropharmacological studies indicates that several drugs which facilitate behavioural recovery from dopamine-depleting lesions may do so by affecting amine release or receptor sensitivity near areas of accumulation rather than depleted terminal fields. We conclude that amine accumulation is a component of dopamine neuron degeneration which should be considered when assessing the role of the central catecholamine systems in the control of various behavioural and physiological processes.
当黑质纹状体和中脑皮质神经元发生退化时，终末区域的多巴胺会减少，并且这些系统的轴突在通过内侧前脑束穿过下丘脑时，胺类物质会在轴突中积累。传统的观点认为，多巴胺神经元退化后出现的运动和完成行为缺陷，是由于终末区域功能性多巴胺神经递质的丧失。然而，我们推测下丘脑胺类物质的积累代表了脑组织的一个区域，在这个区域，诸如神经递质释放、电场传递或局部轴突肿胀等过程可能会影响相邻神经元，从而可能参与行为缺陷的产生。来自对周围和中枢含儿茶酚胺神经元研究的大量证据表明，当它们的轴突退化时，功能性神经递质可能会释放。神经药理学研究的信息表明，几种有助于从多巴胺耗竭性损伤中恢复行为的药物，可能是通过影响积累区域附近的胺类释放或受体敏感性，而不是耗竭的终末区域来实现的。我们得出结论，胺类物质的积累是多巴胺神经元退化的一个组成部分，在评估中枢儿茶酚胺系统在控制各种行为和生理过程中的作用时应予以考虑。
