Bi-phasic change in BDNF gene expression following antidepressant drug treatment.
The gene for brain derived neurotrophic factor (BDNF) has recently received attention in relation to the therapeutic action of antidepressant treatment. This study aimed to clarify the influence of post drug interval on the effect of acute and repeated treatment with antidepressant drugs on BDNF gene expression in the rat brain. It was found that repeated administration of either the monoamine oxidase inhibitor tranylcypromine (TCP) or 5-hydroxytryptamine (5-HT) re-uptake inhibitors (fluoxetine, paroxetine and sertraline), evoke a bi-phasic and time-dependent effect on BDNF gene expression in the rat hippocampus (especially dentate gyrus). A down-regulation of the BDNF gene was detected at 4 h (TCP and fluoxetine) and an up-regulation at 24 h (TCP, paroxetine, fluoxetine, sertraline) after the last of twice daily injections for 14 days. After a single injection the down-regulation was detected at 4 h (TCP, fluoxetine, paroxetine and sertraline) but BDNF mRNA levels were not altered at 24 h post drug (TCP, fluoxetine and paroxetine). Administration of inhibitors of noradrenaline re-uptake (desipramine and maprotiline) or the atypical antidepressant mianserin had no effect on BDNF mRNA levels at either single (4 h post drug, desipramine) or repeated (24 h post drug, desipramine, maprotiline, mianserin) treatment. The gene expression for NT-3, which is distributed in a high density in the dentate gyrus, was not affected by single or repeated injections of antidepressant drugs (TCP, fluoxetine, paroxetine, sertraline, desipramine, maprotiline or mianserin) at 4 or 24 h post drug. In conclusion, these data show that the effect of antidepressant drugs on BDNF gene expression may be more complex and less widespread across treatments than previously thought. Thus, in this study drugs interacting with the central 5-HT system altered BDNF expression but the effect was bi-phasic over the 24 h post drug period.
University Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, UK.
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Coppell
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Pei
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Zetterström
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001345:Autoradiography; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; D008803:Mianserin; D008996:Monoamine Oxidase Inhibitors; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors