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Chronic social stress induces peripheral and central immune activation, blunted mesolimbic dopamine function, and reduced reward-directed behaviour in mice
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Bergamini, Giorgio, Mechtersheimer, Jonas , Azzinnari, Damiano, Sigrist, Hannes, Buerge, Michaela, Dallmann, Robert, Freije, Robert, Kouraki, Alfroditi, Opacka-Juffry, Jolanta, Seifritz, Erich, Ferger, Boris, Suter, Tobias and Pryce, Christopher R. (2018) Chronic social stress induces peripheral and central immune activation, blunted mesolimbic dopamine function, and reduced reward-directed behaviour in mice. Neurobiology of Stress, 8 . pp. 42-56. doi:doi: 10.1016/j.ynstr.2018.01.004
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Official URL: https://doi.org/10.1016/j.ynstr.2018.01.004
Abstract
Psychosocial stress is a major risk factor for depression, stress leads to peripheral and central immune activation, immune activation is associated with blunted dopamine (DA) neural function, DA function underlies reward interest, and reduced reward interest is a core symptom of depression. These states might be inter-independent in a complex causal pathway. Whilst animal-model evidence exists for some specific steps in the pathway, there is currently no animal model in which it has been demonstrated that social stress leads to each of these immune, neural and behavioural states. Such a model would provide important existential evidence for the complex pathway and would enable the study of causality and mediating mechanisms at specific steps in the pathway. Therefore, in the present mouse study we investigated for effects of 15-day resident-intruder chronic social stress (CSS) on each of these states. Relative to controls, CSS mice exhibited higher spleen levels of granulocytes, inflammatory monocytes and T helper 17 cells; plasma levels of inducible nitric oxide synthase; and liver expression of genes encoding kynurenine pathway enzymes. CSS led in the ventral tegmental area to higher levels of kynurenine and the microglia markers Iba1 and Cd11b and higher binding activity of DA D1 receptor; and in the nucleus accumbens (NAcc) to higher kynurenine, lower DA turnover and lower c-fos expression. Pharmacological challenge with DA reuptake inhibitor identified attenuation of DA stimulatory effects on locomotor activity and NAcc c-fos expression in CSS mice. In behavioural tests of operant responding for sucrose reward validated as sensitive assays for NAcc DA function, CSS mice exhibited less reward-directed behaviour. Therefore, this mouse study demonstrates that a chronic social stressor leads to changes in each of the immune, neural and behavioural states proposed to mediate between stress and disruption of DA-dependent reward processing. The model can now be applied to investigate causality and, if demonstrated, underlying mechanisms in specific steps of this immune-neural-behavioural pathway, and thereby to identify potential therapeutic targets.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | B Philosophy. Psychology. Religion > BF Psychology Q Science > QP Physiology |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine | ||||||||||||
| Library of Congress Subject Headings (LCSH): | Stress (Psychology), Immune response, Dopamine | ||||||||||||
| Journal or Publication Title: | Neurobiology of Stress | ||||||||||||
| Publisher: | Elsevier | ||||||||||||
| ISSN: | 2352-2895 | ||||||||||||
| Official Date: | February 2018 | ||||||||||||
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| Volume: | 8 | ||||||||||||
| Page Range: | pp. 42-56 | ||||||||||||
| DOI: | doi: 10.1016/j.ynstr.2018.01.004 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access | ||||||||||||
| RIOXX Funder/Project Grant: |
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