PMID- 19424057
OWN - NLM
STAT- MEDLINE
DCOM- 20090723
LR  - 20151119
IS  - 1473-5849 (Electronic)
IS  - 0955-8810 (Linking)
VI  - 20
IP  - 3
DP  - 2009 May
TI  - Desipramine prevents stress-induced changes in depressive-like behavior and 
      hippocampal markers of neuroprotection.
PG  - 273-85
LID - 10.1097/FBP.0b013e32832c70d9 [doi]
AB  - Extracellular signal-regulated kinases (ERKs) are widely implicated in multiple 
      physiological processes. Although ERK1/2 has been proposed as a common mediator 
      of antidepressant action in naive rodents, it remains to be determined whether 
      the ERK1/2 pathway plays a role in depressive disorder. Here, we investigated 
      whether chronic restraint stress (14 days) and antidepressant treatment 
      [desipramine (DMI), 10 mg/kg intraperitoneally] induce changes in animal behavior 
      and hippocampal levels of phospho-ERK1/2 and its substrate phospho-cAMP response 
      element-binding protein (CREB). The results indicated that stress-induced 
      depressive-like behaviors were correlated with an increase in P-ERK1/2 and P-CREB 
      in the hippocampus evaluated by immunoblot analysis. As an indication of CREB 
      activity, we evaluated changes in mRNA levels of its target genes. Brain-derived 
      neurotrophic factor (BDNF) mRNA was reduced by stress, an effect prevented by DMI 
      only in the CA3 area of hippocampus. Bcl-2 mRNA was reduced in all hippocampal 
      regions by stress, an effect independent of DMI treatment. However, immunoblot 
      from hippocampal extracts revealed that stress increased BCL-2 levels, an effect 
      prevented by chronic DMI. These results suggest that ERKs and BDNF may be altered 
      in depressive disorder, modifications that are sensitive to DMI action. In 
      contrast, the stress-induced increase in BCL-2 may correspond to a 
      neuroprotective response.
FAU - Bravo, Javier A
AU  - Bravo JA
AD  - Laboratory of Neuroplasticity and Neurogenetics, Department of Biochemistry and 
      Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad 
      de Chile, Santiago, Chile.
FAU - Diaz-Veliz, Gabriela
AU  - Diaz-Veliz G
FAU - Mora, Sergio
AU  - Mora S
FAU - Ulloa, Jose L
AU  - Ulloa JL
FAU - Berthoud, Viviana M
AU  - Berthoud VM
FAU - Morales, Paola
AU  - Morales P
FAU - Arancibia, Sandor
AU  - Arancibia S
FAU - Fiedler, Jenny Lucy
AU  - Fiedler JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Behav Pharmacol
JT  - Behavioural pharmacology
JID - 9013016
RN  - 0 (Antidepressive Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - TG537D343B (Desipramine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology/therapeutic use
MH  - Behavior, Animal
MH  - Biomarkers/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/genetics/metabolism
MH  - Desipramine/*pharmacology/therapeutic use
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
MH  - Hippocampus/drug effects/*metabolism
MH  - Injections, Intraperitoneal
MH  - Male
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stress, Psychological/metabolism/*prevention & control/psychology
EDAT- 2009/05/09 09:00
MHDA- 2009/07/25 09:00
CRDT- 2009/05/09 09:00
PHST- 2009/05/09 09:00 [entrez]
PHST- 2009/05/09 09:00 [pubmed]
PHST- 2009/07/25 09:00 [medline]
AID - 10.1097/FBP.0b013e32832c70d9 [doi]
PST - ppublish
SO  - Behav Pharmacol. 2009 May;20(3):273-85. doi: 10.1097/FBP.0b013e32832c70d9.