This study was designed to examine the effects of haloperidol, one of representative antipsychotic drugs, on the expression of c-fos mRNA in cultured embryonic rat hippocampal neurons. On the fourth day of culture, hippocampal neurons were treated with variable concentrations(0μM, 1μM, 10μM, 100μM and 1mM) of haloperidol. After 30 minutes, CRT-PCR(Competitive Reverse Transcriptase-Polymerase Chain Reaction) analysis was used to quantify c-fos mRNA expression.
Experimental results showed that acute and direct treatment with haloperidol with relatively low concentrations(≤1μM) had no inductive effect on the expression of c-fos mRNA in the rat hippocampal neurons. However, after treatment with relatively high concentrations (≥10μM) 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 dealth. Finally, though cell death remains to be confirmed, the inhibition of c-fos induction or cell death could play a role in the cognitive impairments known to be adverse effects of some antipsychotics.
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 resulting from chronic treatment with antipsychotic drugs.
|