Desipramine prevents stress-induced changes in depressive-like behavior and hippocampal markers of neuroprotection

JAVIER ANDRES BRAVO VIVALLO, Gabriela Díaz-Veliz, Sergio Mora, José L. Ulloa, Viviana M. Berthoud, Paola Morales, Sandor Arancibia, Jenny Lucy Fiedler

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

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), 10mg/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.

Original languageEnglish
Pages (from-to)273-285
Number of pages13
JournalBehavioural Pharmacology
Volume20
Issue number3
DOIs
StatePublished - May 2009
Externally publishedYes

Keywords

  • BCL-2
  • Behavior
  • Brain-derived neurotrophic factor
  • camp response element-binding protein
  • Depression
  • Desipramine
  • Extracellular signal-regulated kinase
  • Rat
  • Stress

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