배양한 흰쥐 해마신경세포에서 항우울제에 의한 c-fos mRNA의 발현

Abstract

This study was designed to examine the effects of two antidepresant drugs on the expression of c-fos mRNA in culutred embryonic rat hippocampal neurons. The drugs used were imipramine and amitriptyline. On the fourth day of culture, hippocampal neurons were treated with variable concentrations of each drug. Competitive RT-PCR (reverse transcriptase-PCR) analysis was used to quantify the c-fos mRNA expression induced by each drug. Experimental results showed that acute and direct treatment with imipramine and amitriptyline with relatively low concentrations (imipramine < 10 microM, amitriptyline < 10 microM) had no inductive effect on the expression of c-fos mRNA in the rat hippocampal neurons. However, after treatment with relatively high concentrations (imipramine >100 microM, amitriptyline > 100 microM) c-fos mRNA was not detected. These findings suggest the followings. Firstly, the action mechanisms of these drugs on the hippocampal neurons might not be mediated by c-fos but by other immediate-early genes (IEGs). Secondly, their actions may be mediated indirectly via other areas of the brain. Thirdly, the expression of c-fos might be inhibited by high concentrations of these drugs, or the high concentrations could induce cell death. Finally, though cell death remains to be confirmed, the inhibition of c-fos induction or cell death could paly a role in the cognitive impairments known to be adverse effects of some antidepressants. This study is believed to be a first step toward understanding the mechanisms of learning and memory. Further studies are needed to investigate the expression of various IEGs and changes in the hippocampal neurons of rat resulting from chronic treatment with antidepressant drugs