Chronic stress affects the number of GABAergic neurons in the orbitofrontal cortex of rats

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  • Zsofia Varga, Szentagothai Res Ctr, University of Pecs, MTA PTE, Neurobiol Stress Res Grp
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  • David Csabai, Szentagothai Res Ctr, University of Pecs, MTA PTE, Neurobiol Stress Res Grp
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  • Attila Miseta, Univ Pecs, University of Pecs, Sch Med, Dept Lab Med
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  • Ove Wiborg
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  • Boldizsar Czeh, Aarhus Univ, Aarhus University, Dept Clin Med, Translat Neuropsychiat Unit

Cortical GABAergic dysfunctions have been documented by clinical studies in major depression. We used here an animal model for depression and investigated whether long-term stress exposure can affect the number of GABAergic neurons in the orbitofrontal cortex (OFC). Adult male rats were subjected to 7-weeks of daily stress exposure and behaviorally phenotyped as anhedonic or stress-resilient animals. GABAergic interneurons were identified by immunohistochemistry and systematically quantified. We analyzed calbindin-(CB), calretinin-(CR), cholecystokinin-(CCK), parvalbumin-(PV), neuropeptide Y-(NPY) and somatostatin-positive (SST+) neurons in the following specific subareas of the OFC: medial orbital (MO), ventral orbital (VO), lateral orbital (LO) and dorsolateral orbital (DLO) cortex. For comparison, we also analyzed the primary motor cortex (M1) as a non-limbic cortical area. Stress had a pronounced effect on CB+ neurons and reduced their densities by 40-50% in the MO, VO and DLO. Stress had no effect on CCK+, CR+, PV+, NPY+ and SST+ neurons in any cortical areas. None of the investigated GABAergic neurons were affected by stress in the primary motor cortex. Interestingly, in the stress-resilient animals, we observed a significantly increased density of CCK+ neurons in the VO. NPY+ neuron densities were also significantly different between the anhedonic and stress-resilient rats, but only in the LO. Our present data demonstrate that chronic stress can specifically reduce the density of calbindin-positive GABAergic neurons in the orbitofrontal cortex and suggest that NPY and CCK expression in the OFC may relate to the stress resilience of the animals. (C) 2016 Elsevier B.V. All rights reserved.

Original languageEnglish
JournalBehavioural Brain Research
Volume316
Pages (from-to)104-114
Number of pages11
ISSN0166-4328
DOIs
Publication statusPublished - 1 Jan 2017

    Research areas

  • Calbindin, Cholecystokinin, Chronic mild stress, Mood disorder, Motor cortex, Neuropeptide Y, MEDIAL PREFRONTAL CORTEX, MAJOR DEPRESSIVE DISORDER, CHRONIC MILD STRESS, CALCIUM-BINDING PROTEINS, NEUROPEPTIDE-Y, DENDRITIC MORPHOLOGY, INHIBITORY DEFICITS, BIPOLAR DISORDER, MODEL, CHOLECYSTOKININ

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