| Desipramine prevents stress-induced changes in depressive-like behavior and hippocampal markers of neuroprotection. | |
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MedLine Citation:
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PMID: 19424057 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Javier A Bravo; Gabriela Díaz-Veliz; Sergio Mora; José L Ulloa; Viviana M Berthoud; Paola Morales; Sandor Arancibia; Jenny Lucy Fiedler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Behavioural pharmacology Volume: 20 ISSN: 1473-5849 ISO Abbreviation: Behav Pharmacol Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-19 Completed Date: 2009-07-23 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9013016 Medline TA: Behav Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 273-85 Citation Subset: IM |
Affiliation:
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Laboratory of Neuroplasticity and Neurogenetics, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago, Chile. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antidepressive Agents / pharmacology*, therapeutic use Behavior, Animal Biological Markers / metabolism Brain-Derived Neurotrophic Factor / genetics, metabolism* Cyclic AMP Response Element-Binding Protein / genetics, metabolism Desipramine / pharmacology*, therapeutic use Extracellular Signal-Regulated MAP Kinases / genetics, metabolism Hippocampus / drug effects, metabolism* Injections, Intraperitoneal Male Neuroprotective Agents / pharmacology*, therapeutic use RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Stress, Psychological / metabolism, prevention & control*, psychology |
| Chemical | |
Reg. No./Substance:
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0/Antidepressive Agents; 0/Biological Markers; 0/Brain-Derived Neurotrophic Factor; 0/Cyclic AMP Response Element-Binding Protein; 0/Neuroprotective Agents; 0/RNA, Messenger; 50-47-5/Desipramine; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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