The differential regulation of BDNF and TrkB levels in juvenile rats after four days of escitalopram and desipramine treatment.
Major depressive disorder is a major health problem in adults and is now recognized as a substantial problem in children as well. Tricyclic antidepressants, including desipramine (DMI), are no better than placebo in treating childhood and adolescent depression, but are effective in treating adult depression. Several studies have suggested that normal BDNF (brain-derived neurotrophic factor) signaling is necessary for antidepressant drug action. Antidepressant drugs induce several plastic changes in the rodent brain which may be associated with changes in BDNF levels and/or with BDNF function. In the present study we report parallel measurements of BDNF mRNA and protein in the frontal cortex and hippocampus after four days of twice daily treatments with escitalopram, a selective serotonin reuptake inhibitor, and desipramine, a tricyclic antidepressant. Post-natal day 13, 21, 28 and adult rats were used in this study. TrkB (the primary receptor for BDNF) mRNA levels were also examined under the same treatment conditions. BDNF mRNA and protein levels, as well as TrkB mRNA levels, were increased significantly in post-natal day 13 pups after escitalopram treatment as compared to control, but desipramine failed to increase either BDNF or TrkB. The failure of desipramine to increase BDNF and TrkB levels in juvenile rats is consistent with the lack of efficacy of desipramine in children and adolescents. The serotonergic nervous system matures earlier than the noradrenergic system, which may explain why escitalopram, but not desipramine, increases BDNF and TrkB levels.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198-5800, USA. megankozisek@yahoo.com
Megan E
ME
Kozisek
David
D
Middlemas
David B
DB
Bylund
D000375:Aging / Q000378:metabolism; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002851:Chromatography, High Pressure Liquid; D015283:Citalopram / Q000493:pharmacokinetics / Q000494:pharmacology*; D003891:Desipramine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000378:metabolism; D007274:Injections, Intraperitoneal; D017397:Prefrontal Cortex / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D020813:Receptor, trkB / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; D015283:Citalopram; D003891:Desipramine; D012333:RNA, Messenger; D020813:Receptor, trkB; D017367:Selective Serotonin Reuptake Inhibitors