Murrin L Charles, Sanders Jeff D, Bylund David B
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800, USA.
Biochem Pharmacol. 2007 Apr 15;73(8):1225-36. doi: 10.1016/j.bcp.2007.01.028. Epub 2007 Jan 25.
Our understanding of the development of neurotransmitter systems in the central nervous system has increased greatly over the past three decades and it has become apparent that drug effects on the developing nervous system may differ considerably from effects on the mature nervous system. Recently it has become clear there are significant differences in the effectiveness of antidepressant drug classes in children and adolescents compared to adults. Whereas the selective serotonin reuptake inhibitors are effective in treating all ages from children to adults, the tricyclic antidepressants, many of which inhibit norepinephrine reuptake, have been shown to be ineffective in treating children and adolescents even though they are effective in adults. We review here the development of the noradrenergic and serotonergic nervous systems, both in terms of neurotransmitter system markers and function. Both of these neurotransmitter systems are primary targets of antidepressant medications as well as of central nervous system stimulants. It is clear from a comparison of their development that the serotonin system reaches maturity much earlier than the norepinephrine system. We suggest this may help explain the differences in response to antidepressants in children and adolescents compared to adults. In addition, these differences suggest that drugs acting preferentially on either neurotransmitter system may impact the normal course of CNS development at different time points. Consideration of such differences in the development of neurotransmitter systems may be of significance in optimizing treatments for a variety of centrally mediated disorders.
在过去三十年中，我们对中枢神经系统中神经递质系统发育的理解有了极大的提高，并且已经很明显，药物对发育中的神经系统的影响可能与对成熟神经系统的影响有很大差异。最近很清楚的是，与成年人相比，抗抑郁药物类别在儿童和青少年中的有效性存在显著差异。虽然选择性5-羟色胺再摄取抑制剂对从儿童到成年人的所有年龄段都有效，但许多三环类抗抑郁药抑制去甲肾上腺素再摄取，已被证明对治疗儿童和青少年无效，尽管它们对成年人有效。我们在此回顾去甲肾上腺素能和5-羟色胺能神经系统的发育，包括神经递质系统标志物和功能方面。这两种神经递质系统都是抗抑郁药物以及中枢神经系统兴奋剂的主要靶点。从它们发育的比较中可以清楚地看出，5-羟色胺系统比去甲肾上腺素系统成熟得早得多。我们认为，这可能有助于解释儿童和青少年与成年人相比对抗抑郁药反应的差异。此外，这些差异表明，优先作用于任何一种神经递质系统的药物可能在不同时间点影响中枢神经系统发育的正常进程。考虑神经递质系统发育中的此类差异可能对优化各种中枢介导疾病的治疗具有重要意义。
