Competitive and non-competitive NMDA receptor antagonists induce c-Fos expression in the rat anterior, cingulate cortex.

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.