Corticosterone regulates pERK1/2 map kinase in a chronic depression model.
Neurotransmitter- or neurotrophin-regulated intracellular signaling in the hippocampus is hypothesized to contribute to depression and antidepressant (ADT) efficacy. Extracellular signal-regulated kinase 1/2 (ERK1/2) is downstream of several receptor types and regulates transcriptional activity of many targets; ERK1/2 may thereby influence mood and affect. Using a novel, ADT-sensitive depression model in mice, we show that prior corticosterone exposure decreases motivated behavior, sucrose consumption, and pERK1/2 in the dentate gyrus, but not in CA1/CA3. Notably, prefrontal cortical targets were also regulated. Our data suggest ADTs restore hippocampal pERK1/2 after stress-related insult, and potentially reveal a novel role for prefrontal neurotrophins in depressive-like symptomology.
Gourley
Shannon L
SL
Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut, USA.
Wu
Florence J
FJ
Taylor
Jane R
JR
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003216:Conditioning, Operant; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D003345:Corticosterone