Fluharty S J, Vollmer R R, Meyers S A, McCann M J, Zigmond M J, Stricker E M
Department of Behavioral Neuroscience, University of Pittsburgh, Pennsylvania.
J Pharmacol Exp Ther. 1987 Nov;243(2):415-23.
In pithed rats, neurally mediated chronotropic responses to thoracolumbar stimulation were reduced substantially 1 day after animals were treated with the neurotoxin 6-hydroxydopamine (6-HDA), which produced a subtotal destruction of postganglionic sympathetic nerve terminals. However, the chronotropic responses of 6-HDA-treated rats recovered to near normal within 1 week despite 90% depletion of cardiac norepinephrine (NE). This recovery of function appeared to depend upon function in surviving sympathetic nerves, and was associated with increased synthesis and release of NE from those neurons as well as diminished inactivation of NE. The gradual development of post-junctional changes, most notably an increase in the density of myocardial beta adrenergic receptors, resulted in enhanced sensitivity to NE and contributed to cardiac function 3 weeks after 6-HDA treatment. In addition, the adrenal medulla increased its synthesis of catecholamines after 6-HDA treatment and thereby contributed to cardiac function, which was especially evident during prolonged sympathoadrenal stimulation. Some of these same adaptations have been observed when rats are subjected to chronic stress, and thus common mechanisms of neuroplasticity may mediate the sympathoadrenal responses to stress and to subtotal injury.
在脊髓被切断的大鼠中，在用神经毒素6-羟基多巴胺（6-HDA）处理动物1天后，神经介导的对胸腰段刺激的变时反应显著降低，6-HDA使节后交感神经末梢发生部分破坏。然而，尽管心脏去甲肾上腺素（NE）耗竭了90%，但6-HDA处理的大鼠的变时反应在1周内恢复到接近正常水平。这种功能恢复似乎依赖于存活交感神经的功能，并且与这些神经元中NE的合成和释放增加以及NE失活减少有关。节后变化的逐渐发展，最显著的是心肌β-肾上腺素能受体密度的增加，导致对NE的敏感性增强，并在6-HDA处理3周后有助于心脏功能。此外，6-HDA处理后肾上腺髓质增加了儿茶酚胺的合成，从而有助于心脏功能，这在长时间交感-肾上腺刺激期间尤为明显。当大鼠受到慢性应激时，也观察到了一些相同的适应性变化，因此神经可塑性的共同机制可能介导了交感-肾上腺对应激和部分损伤的反应。
