Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expressionafter chronic treatment with different subclasses of antidepressants in the rat

There is a latency period of several weeks before the onset of clinical eff ect of antidepressant drugs. The detailed mechanisms underlying drug-induce d adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated r ats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In s itu hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the g lucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profou ndly in the hippocampal formation and the cerebral cortex after all drug tr eatments, especially after moclobemide treatment (77-122% increase), with t he exception of buspirone. MR mRNA expression was induced in hippocampal CA 1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-O H-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 su bfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatm ent. There ale selective effects of antidepressant drugs on specific transc ription factors. These may be important fur adaptive neuronal and neuroendo crine changes after antidepressant treatment including HPA axis negative fe edback regulation.