Selective effects on NGFI-A, MR, GR and NGFI-B hippocampal mRNA expression after chronic treatment with different subclasses of antidepressants in the rat.
There is a latency period of several weeks before the onset of clinical effect of antidepressant drugs. The detailed mechanisms underlying drug-induced adaptive neuronal changes are not known. To elucidate the involvement of changes in gene expression of candidate transcription factors, we treated rats for 21 days with buspirone, fluoxetine, 8-OH-DPAT and moclobemide. In situ hybridization was used to study mRNAs encoding NGFI-A, NGFI-B and the glucocorticoid receptors, MR and GR. NGFI-A mRNA expression increased profoundly in the hippocampal formation and the cerebral cortex after all drug treatments, especially after moclobemide treatment (77-122% increase); with the exception of buspirone. MR mRNA expression was induced in hippocampal CA1/CA2 subregions (27-37%) by all antidepressants, while moclobemide and 8-OH-DPAT significantly increased GR gene expression mainly in the CA1 region (31-44%). NGFI-B mRNA was significantly decreased in the hippocampal CA3 subfield (23%) and restrosplenial granular cortex (38%) by moclobemide treatment. There are selective effects of antidepressant drugs on specific transcription factors. These may be important for adaptive neuronal and neuroendocrine changes after antidepressant treatment including HPA axis negative feedback regulation.
Bjartmar
L
L
Department of Neuroscience and Locomotion, Linköping University Hospital, Sweden.
Johansson
I M
IM
Marcusson
J
J
Ross
S B
SB
Seckl
J R
JR
Olsson
T
T
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017874:Immediate-Early Proteins; D008297:Male; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis / Q000235:genetics; D011987:Receptors, Steroid; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D000928:Antidepressive Agents; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D014157:Transcription Factors