Wedzony K, Czyrak A
Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.
J Physiol Pharmacol. 1996 Sep;47(3):525-33.
In the present study we tried to find out whether the competitive NMDA receptor antagonist CGP 40116 was capable of inducing c-Fos expression in the rat cingulate cortex in a manner similar to that described previously for the non-competitive NMDA receptor antagonist MK-801. Induction of fast early genes by MK-801, especially in the rat cortex, has recently been linked with the neurotoxic effects of non-competitive NMDA receptor antagonists on cortical neurones, hence it was of interest to extend those studies to another class of NMDA receptors antagonists i.e., competitive one. It was found that CGP 40116 (2.5 and 5 mg/kg) induced c-Fos expression in the rat anterior cingulate cortex. That effect was dose-dependent and was shown as an increase in the number of cells expressing the c-Fos immunoreactivity. A qualitatively similar, but quantitatively stronger, effect was observed after administration of MK-801 (0.2 and 0.4 mg/kg), which also caused a dose-dependent increase in the number of c-Fos positive neurones. The described dose-dependent effects of CGP 40116 and MK-801 are shown as an increase in the number of c-Fos-positive neurones, but not as an increase in the optical density of c-Fos immunostaining in c-Fos positive neurones. In control, vehicle-injected rats, the constitutive c-Fos immunoreactivity was not found in the rat anterior cingulate cortex. The obtained data indicate that both competitive and non-competitive NMDA receptor antagonists may induce similar effects on the c-Fos immunoreactivity in the rat anterior cingulate cortex, and that their administration may lead to similar functional consequences resulting form activation of fast, early genes.
在本研究中，我们试图探究竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂CGP 40116是否能够像先前描述的非竞争性NMDA受体拮抗剂MK-801那样，诱导大鼠扣带回皮质中c-Fos的表达。最近发现，MK-801对快速早期基因的诱导作用，尤其是在大鼠皮质中，与非竞争性NMDA受体拮抗剂对皮质神经元的神经毒性作用有关，因此将这些研究扩展到另一类NMDA受体拮抗剂即竞争性拮抗剂是很有意义的。结果发现，CGP 40116（2.5和5毫克/千克）可诱导大鼠前扣带回皮质中c-Fos的表达。这种作用呈剂量依赖性，表现为表达c-Fos免疫反应性的细胞数量增加。给予MK-801（0.2和0.4毫克/千克）后观察到了定性相似但定量更强的作用，MK-801也导致c-Fos阳性神经元数量呈剂量依赖性增加。CGP 40116和MK-801所描述的剂量依赖性作用表现为c-Fos阳性神经元数量的增加，而不是c-Fos阳性神经元中c-Fos免疫染色光密度的增加。在对照的注射赋形剂的大鼠中，未在前扣带回皮质中发现组成型c-Fos免疫反应性。获得的数据表明，竞争性和非竞争性NMDA受体拮抗剂均可对大鼠前扣带回皮质中的c-Fos免疫反应性产生相似的影响，并且它们的给药可能导致由快速早期基因激活引起的相似功能后果。
