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Stress-induced anhedonia is associated with the activation of the inflammatory system in the rat brain: Restorative effect of pharmacological intervention.
- Source :
-
Pharmacological research [Pharmacol Res] 2016 Jan; Vol. 103, pp. 1-12. Date of Electronic Publication: 2015 Nov 01. - Publication Year :
- 2016
-
Abstract
- Major depression is a complex disease that originates from the interaction between a genetic background of susceptibility and environmental factors such as stress. At molecular level, it is characterized by dysfunctions of multiple systems including neurotransmitters, hormones, signalling pathways, neurotrophic and neuroplastic molecules and - more recently - inflammatory mediators. Accordingly, in the present study we used the chronic mild stress (CMS) paradigm in the rat to elucidate to what extent brain inflammation may contribute to the development and/or the maintenance of an anhedonic phenotype and how pharmacological intervention may interfere with such behavioral and molecular stress-induced alterations. To this aim, adult male rats were exposed to CMS for 2 weeks and the cerebral expression of several mediators of the inflammatory system was evaluated in the hippocampus and prefrontal cortex of both stressed and control animals in parallel with the sucrose intake. Next, the animals that showed a decreased sucrose consumption were exposed to five further weeks of CMS and treated with the antidepressants imipramine or agomelatine, or the antipsychotic lurasidone. Our results demonstrate that only the stressed animals that were characterized by a deficit in sucrose intake showed increased expression of the pro-inflammatory cytokines IL-1β, IL-6 and up-regulation of markers and mediators of microglia activation such as CD11b, CX3CL1 and its receptor CX3CR1 in comparison with stress-resilient animals. Some of these molecular alterations persisted also after longer stress exposure and were modulated, similarly to the behavioral effects of CMS, by chronic pharmacological treatment. These data suggest that neuroinflammation may have a key role in the pathological consequences of stress exposure, thus contributing to the subject's vulnerability for depression.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Acetamides pharmacology
Animals
Antidepressive Agents pharmacology
Antipsychotic Agents pharmacology
CD11b Antigen genetics
CD11b Antigen metabolism
CX3C Chemokine Receptor 1
Chemokine CX3CL1 genetics
Gene Expression Profiling
Hippocampus metabolism
Imipramine pharmacology
Interleukin-1beta genetics
Interleukin-6 genetics
Lurasidone Hydrochloride pharmacology
Male
Prefrontal Cortex metabolism
RNA, Messenger metabolism
Rats, Wistar
Receptors, Chemokine genetics
Transforming Growth Factor beta genetics
Anhedonia physiology
Brain metabolism
Stress, Physiological physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-1186
- Volume :
- 103
- Database :
- MEDLINE
- Journal :
- Pharmacological research
- Publication Type :
- Academic Journal
- Accession number :
- 26535964
- Full Text :
- https://doi.org/10.1016/j.phrs.2015.10.022