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

Bravo, JA; Diaz-Veliz, G; Mora S.; Ulloa, JL.; Berthoud VM.; Morales P.; Arancibia S.; Fiedler, JL

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.

Más información

Título según WOS: Desipramine prevents stress-induced changes in depressive-like behavior and hippocampal markers of neuroprotection
Título según SCOPUS: Desipramine prevents stress-induced changes in depressive-like behavior and hippocampal markers of neuroprotection
Título de la Revista: BEHAVIOURAL PHARMACOLOGY
Volumen: 20
Número: 3
Editorial: LIPPINCOTT WILLIAMS & WILKINS
Fecha de publicación: 2009
Página de inicio: 273
Página final: 285
Idioma: English
URL: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00008877-200905000-00007
DOI:

10.1097/FBP.0b013e32832c70d9

Notas: ISI, SCOPUS