Desipramine prevents stress-induced changes in depressive-like behavior and hippocampal markers of neuroprotection.
Behav Pharmacol
; 20(3): 273-85, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19424057
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), 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Estresse Psicológico
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Fármacos Neuroprotetores
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Fator Neurotrófico Derivado do Encéfalo
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Desipramina
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Hipocampo
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Antidepressivos
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article