The effects of chronic antidepressant treatment on gene expression in the brain

Although the acute action of antidepressant treatment is associated with monoamine re-uptake inhibition, the molecular adaptations underlying the therapeutic action of these agents have still to be determined. Chronic administration of desipramine, fluoxetine and tranylcypromine has been shown to up-regulate the cAMP signal transduction cascade resulting in increased expression and function of the transcription factor CRE binding protein (CREB), in various regions of the brain, particularly the cerebral cortex and hippocampus. In turn, enhanced CREB expression leads to an upregulation in cAMP response element (CRE )-mediated gene transcription in these areas. For example, brain-derived neurotrophic factor (BDNF) expression is increased in the hippocampus. Studies have also demonstrated that expression of other transcription factors (NGF1-A, mineralocorticoid receptor (MR), glucocorticoid receptor (GR), c-Fos) is increased following treatment with a similar range of antidepressant drugs. Decreases in mRNA of corticotrophin-releasing factor (CRF) and its receptor CRF-R1 have been detected in the hypothalamus and amygdala, respectively, following chronic amitriptyline administration. Moclobemide causes decreased expression of the transcription factor NGF1-B in the hippocampus.

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