| Beneficial effects of desipramine on cognitive function of chronically stressed rats are mediated by alpha1-adrenergic receptors in medial prefrontal cortex. | |
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MedLine Citation:
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PMID: 20417676 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic stress is a risk factor for many psychopathological conditions, including depression and anxiety disorders. Cognitive impairments associated with prefrontal cortical dysfunction are a major component of such illnesses. Using an attentional set-shifting test (AST), we have previously shown that elevating noradrenergic activity in rat medial prefrontal cortex (mPFC) can facilitate cognitive set-shifting, and that chronic unpredictable stress (CUS) caused set-shifting deficits. It is not known, however, if noradrenergic modulatory function is compromised by chronic stress, perhaps contributing to the stress-induced cognitive deficit. Thus, the first study investigated whether acutely elevating noradrenergic activity in mPFC still enhances cognitive function after chronic stress. As previously demonstrated, CUS impaired cognitive set-shifting on the AST. This deficit was abolished by acute systemic administration of the alpha(2)-adrenergic autoreceptor antagonist, atipamezole. Microdialysis revealed no differences in extracellular norepinephrine (NE) levels in mPFC of CUS-exposed and unstressed control rats at baseline or during behavioral testing, and comparable increases after atipamezole. In the second experiment, rats were treated chronically with the selective NE reuptake blocker, desipramine, during the CUS treatment through behavioral testing. Again, CUS impaired cognitive set-shifting in vehicle-treated rats, and chronic desipramine treatment prevented such deficits. Acute blockade of post-synaptic alpha(1)-adrenergic receptors in mPFC prior to testing blocked the beneficial effect of desipramine on cognitive set-shifting. These results suggest that desipramine restores cognitive set-shifting capability that has been compromised by chronic stress by activating alpha(1)-adrenergic receptors in the mPFC. Thus, noradrenergic modulatory capability in mPFC remains intact after CUS, and this represents one possible substrate by which antidepressants may exert their beneficial effects in the treatment of depression. |
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Authors:
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Corina O Bondi; Julianne D Jett; David A Morilak |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-24 |
Journal Detail:
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Title: Progress in neuro-psychopharmacology & biological psychiatry Volume: 34 ISSN: 1878-4216 ISO Abbreviation: Prog. Neuropsychopharmacol. Biol. Psychiatry Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-26 Completed Date: 2010-11-02 Revised Date: 2011-08-17 |
Medline Journal Info:
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Nlm Unique ID: 8211617 Medline TA: Prog Neuropsychopharmacol Biol Psychiatry Country: England |
Other Details:
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Languages: eng Pagination: 913-23 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic Uptake Inhibitors
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pharmacology Analysis of Variance Animals Attention / drug effects Cognition / drug effects* Desipramine / pharmacology* Male Microdialysis Prefrontal Cortex / drug effects, metabolism* Random Allocation Rats Rats, Sprague-Dawley Receptors, Adrenergic, alpha-1 / metabolism* Restraint, Physical Set (Psychology) Stress, Physiological* Stress, Psychological* |
| Grant Support | |
ID/Acronym/Agency:
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MH053851/MH/NIMH NIH HHS; MH072672/MH/NIMH NIH HHS; R01 MH053851-13/MH/NIMH NIH HHS; R01 MH053851-14/MH/NIMH NIH HHS; R01 MH072672-05/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic Uptake Inhibitors; 0/Receptors, Adrenergic, alpha-1; 50-47-5/Desipramine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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