Differential induction of neurotensin and c-fos gene expression by typical versus atypical antipsychotics.
Differential induction of neurotensin and c-fos gene expression by typical versus atypical antipsychotics.
复制标题
典型与非典型抗精神病药对神经降压素和 c-fos 基因表达的差异诱导。
DOI：
10.1073/pnas.90.8.3447
复制
发表时间：
1993
影响因子：
11.1
通讯作者：
Dorsa,DM
中科院分区：
文献类型：
--
作者：
Merchant,KM;Dorsa,DM
精神障碍的病理生理学和药物治疗背后的精确神经机制在很大程度上仍然未知。目前的研究调查的影响，各种抗精神病药物的基因编码的内源性抗精神病药样肽神经降压素（NT）在纹状体的大鼠大脑的区域。结果表明，几种临床上有效的抗精神病药物选择性和特异性地增加NT/神经介肽N（NT/N）mRNA的表达，在壳的脑桥核，一个区域的前脑与边缘系统。另一方面，只有典型的抗精神病药物，导致高发病率的急性运动副作用增加的NT/N mRNA的表达在背外侧纹状体，锥体外系区主要参与运动控制。此外，似乎不同的机制可能涉及抗精神病药物对NT/N基因表达的影响，在背外侧纹状体与海马壳。因此，抗精神病药诱导的NT/N mRNA表达的增加，在背外侧纹状体的c-fos mRNA的快速和短暂的激活之前，而没有一种抗精神病药影响c-fos mRNA的表达在延髓壳。由典型与非典型抗精神病药物诱导的NT/N基因表达的解剖学特征提高了特定NT神经元的活性增加可能有助于这些药物的治疗效果（中脑壳中的NT神经元）或运动副作用（背外侧纹状体中的NT神经元）的可能性。
Precise neural mechanisms underlying the pathophysiology and pharmacotherapy of psychotic disorders remain largely unknown. Present studies investigated the effects of various antipsychotic drugs on expression of the gene encoding the purported endogenous antipsychotic-like peptide neurotensin (NT) in striatal regions of the rat brain. The results demonstrate that several clinically efficacious antipsychotic drugs selectively and specifically increase expression of NT/neuromedin N (NT/N) mRNA in the shell of the nucleus accumbens, a region of the forebrain associated with limbic systems. On the other hand, only typical antipsychotics that cause a high incidence of acute motor side effects increased the expression of NT/N mRNA in the dorsolateral striatum, an extrapyramidal region primarily involved in motor control. In addition, it appears that distinct mechanisms may be involved in the effects of antipsychotics on NT/N gene expression in the dorsolateral striatum versus the accumbal shell. Thus neuroleptic-induced increases in NT/N mRNA expression in the dorsolateral striatum were preceded by a rapid and transient activation of c-fos mRNA, whereas none of the antipsychotics affected c-fos mRNA expression in the accumbal shell. The anatomical characteristics of NT/N gene expression induced by typical versus atypical antipsychotics raise the possibility that increased activity of specific NT neurons may contribute to the therapeutic effects (NT neurons in the accumbal shell) or motor side effects (NT neurons in the dorsolateral striatum) of these drugs.