Enhanced BDNF signaling is associated with an antidepressant-like behavioral response and changes in brain monoamines.
1. Neurotrophins and serotonin have both been implicated in the pathophysiology of depression and in the mechanisms of antidepressant treatments. 2. Brain-derived neurotrophic factor (BDNF) influences the growth and plasticity of serotonergic (5-HT) neurons via the activation of trkB receptor. 3. Transgenic mice overexpressing the full-length trkB receptor (TrkB.TK+) and showing increased trkB activity in brain, and their wild type (WT) littermates, were injected with the antidepressant fluoxetine or saline, and analyzed behaviorally in the forced swimming test paradigm and biochemically for the concentrations of brain monoamines and their metabolites. 4. The TrkB.TK+ mice displayed increased latency to immobility in the forced swim test, suggesting resistance to behavioral despair. 5. Fluoxetine increased the latency to immobility in wild-type mice to a similar level as seen in the trkB.TK+ mice after saline treatment, but had no further behavioral effect in the swimming behavior of the trkB.TK+ mice. 6. Only minor differences in the levels of brain monoamines and their metabolites were observed between the transgenic and wild-type mice. 7. These data, together with other recent observations, suggest that trkB activation may play a critical role in the behavioral responses to antidepressant drugs in mice.
Koponen
Eija
E
Department of Neurobiology, A.I. Virtanen Institute, University of Kuopio, Finland.
Rantamäki
Tomi
T
Voikar
Vootele
V
Saarelainen
Tommi
T
MacDonald
Ewen
E
Castrén
Eero
E
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013315:Stress, Psychological; D013550:Swimming
D018687:Antidepressive Agents, Second-Generation; D019208:Brain-Derived Neurotrophic Factor; D005473:Fluoxetine; D020813:Receptor, trkB; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors