Dismukes R K, Daly J W
J Cyclic Nucleotide Res. 1976 Sep-Oct;2(5):321-36.
The concept of subsensitivity and supersensitivity as a mechanism of neuronal adaptation to alterations in synaptic activity in the brain is an attractive one. However, the complexity of the central nervous system has made it difficult to determine the cellular basis of apparent changes in neuronal excitability resulting from alterations in synaptic input (cf. ref. 83). It now seems that, at least for inhibitory central pathways in which cyclic AMP-generating systems mediate postsynaptic receptor-responses, alterations in synaptic input lead in rat cortex to predictable super- or subsensitivity of the norepinephrine-sensitive cyclic AMP-systems. Supersensitivity of histamine-sensitive cyclic AMP-systems also occurs in rat cortex as a result of apparent lesions of histaminergic tracts. The reason that supersensitivity does not develop to norepinephrine and histamine in guinea pig cortex after similar "denervations" is not known, but is central to an understanding of the factors involved in the role of cyclic AMP-mechanisms to the adaptive plasticity of the central nervous system. However, even before an understanding of all the factors involved in alterations in cyclic AMP-responses in brain tissue is obtained, studies on the effects of environmental and drug-manipulations can provide insights both into the central roles for cyclic AMP-mechanisms and into the nature of drug action. Clearly, an understanding of the interelationships of synaptic input and adaptive changes in postsynaptic cyclic AMP-systems and the exploitation of such knowledge for the elucidation of central adaptive function is an exciting challenge for future research.
作为神经元适应大脑突触活动变化的一种机制，亚敏感性和超敏感性的概念很有吸引力。然而，中枢神经系统的复杂性使得确定因突触输入改变而导致的神经元兴奋性明显变化的细胞基础变得困难（参见参考文献83）。现在看来，至少对于其中环磷酸腺苷生成系统介导突触后受体反应的抑制性中枢通路而言，突触输入的改变在大鼠皮层中会导致去甲肾上腺素敏感的环磷酸腺苷系统出现可预测的超敏感性或亚敏感性。组胺敏感的环磷酸腺苷系统在大鼠皮层中也会因组胺能神经束的明显损伤而出现超敏感性。在豚鼠皮层中，经过类似的“去神经支配”后，对去甲肾上腺素和组胺没有产生超敏感性的原因尚不清楚，但这是理解环磷酸腺苷机制在中枢神经系统适应性可塑性中所涉及因素的关键。然而，即使在尚未了解脑组织中环磷酸腺苷反应改变所涉及的所有因素之前，关于环境和药物操作影响的研究也能为环磷酸腺苷机制的核心作用以及药物作用的本质提供见解。显然，理解突触输入与突触后环磷酸腺苷系统适应性变化之间的相互关系，并利用这些知识阐明中枢适应性功能，是未来研究面临的一项令人兴奋的挑战。
