Ionov Ilya D, Pushinskaya Irina I, Roslavtseva Larissa A, Severtsev Nicholas N
Centre on Theoretical Problems in Physical and Chemical Pharmacology, Russian Academy of Sciences, Moscow, Russia.
Timpharm LTD, Moscow, Russia.
Brain Res. 2018 Jul 15;1691:26-33. doi: 10.1016/j.brainres.2018.04.016. Epub 2018 Apr 20.
A decrease in somatostatin activity is observed in the Parkinsonian brain. In recent experiments on rats, we simulated this abnormality by intracerebroventricular injections of a somatostatin antagonist, cyclosomatostatin. The treated animals displayed catalepsy, a state that resembles the extrapyramidal signs of Parkinson's disease. The neuroanatomical substrates mediating the catalepsy-inducing effect of cyclosomatostatin are unknown. To clarify this issue, we assessed here the action of cyclosomatostatin injected into the substantia nigra pars compacta (SNc), dorsal striatum (DS), locus coeruleus (LC), pedunculopontine tegmental nucleus (PPTg), and inferior colliculus (IC). The experiments were conducted with male Wistar rats of 270-290 g bw, catalepsy was evaluated by using the bar test. The injections into the PPTg and IC were without effect whereas the intra-SNc, intra-DS, and intra-LC administrations produced distinct cataleptic response. Thus, it was shown for the first time that the LC is a brain center capable of causing catalepsy. These data provide new insights into the neuroanatomical organization of the catalepsy-initiating mechanism and suggest the LC representing a potential target for therapeutic manipulations of extrapyramidal dysfunctions.
在帕金森病患者的大脑中观察到生长抑素活性降低。在最近对大鼠的实验中,我们通过脑室内注射生长抑素拮抗剂环生长抑素来模拟这种异常情况。接受治疗的动物表现出僵住症,这是一种类似于帕金森病锥体外系症状的状态。介导环生长抑素诱导僵住症效应的神经解剖学底物尚不清楚。为了阐明这个问题,我们在此评估了注射到黑质致密部(SNc)、背侧纹状体(DS)、蓝斑(LC)、脚桥被盖核(PPTg)和下丘(IC)的环生长抑素的作用。实验使用体重为270 - 290克的雄性Wistar大鼠进行,通过杆式试验评估僵住症。向PPTg和IC注射没有效果,而向SNc内、DS内和LC内给药产生了明显的僵住症反应。因此,首次表明LC是一个能够引起僵住症的脑区。这些数据为僵住症起始机制的神经解剖学组织提供了新的见解,并表明LC是锥体外系功能障碍治疗操作的一个潜在靶点。