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Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response

Mariusz Papp, Piotr Gruca, Magdalena Lason, Ewa Litwa, Wojciech Solecki, Paul Willner

Journal of Psychopharmacology, Volume: 35, Issue: 10, Pages: 1253 - 1264

Swansea University Author: Paul Willner

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DOI (Published version): 10.1177/02698811211048281

Abstract

Background:: There is extensive evidence that antidepressant drugs restore normal brain function by repairing damage to ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). While the damage is more extensive in hippocampus, the evidence of treatments, such as deep brain stimulation, sugge...

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Published in: Journal of Psychopharmacology
ISSN: 0269-8811 1461-7285
Published: SAGE Publications 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa58386
first_indexed 2021-10-18T14:16:19Z
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spelling 2021-11-03T14:17:29.7257068 v2 58386 2021-10-18 Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response 4c278ffb6e4af6ab8816be40af66ecd3 Paul Willner Paul Willner true false 2021-10-18 PSYS Background:: There is extensive evidence that antidepressant drugs restore normal brain function by repairing damage to ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). While the damage is more extensive in hippocampus, the evidence of treatments, such as deep brain stimulation, suggests that functional changes in prefrontal cortex may be more critical. We hypothesized that antidepressant non-response may result from an insufficiency of transmission from vHPC to mPFC. Method:: Antidepressant non-responsive Wistar Kyoto (WKY) rats were subjected to chronic mild stress (CMS), then treated with chronic daily administration of the antidepressant drug venlafaxine (VEN) and/or repeated weekly optogenetic stimulation (OGS) of afferents to mPFC originating from vHPC or dorsal HPC (dHPC). Results:: As in many previous studies, CMS decreased sucrose intake, open-arm entries on the elevated plus maze (EPM), and novel object recognition (NOR). Neither VEN nor vHPC–mPFC OGS alone was effective in reversing the effects of CMS, but the combination of chronic VEN and repeated OGS restored normal behaviour on all three measures. dHPC–mPFC OGS restored normal behaviour in the EPM and NOR test irrespective of concomitant VEN treatment, and had no effect on sucrose intake. Conclusions:: The synergism between VEN and vHPC–mPFC OGS supports the hypothesis that the antidepressant non-responsiveness of WKY rats results from a failure of antidepressant treatment fully to restore transmission in the vHPC–mPFC pathway. Journal Article Journal of Psychopharmacology 35 10 1253 1264 SAGE Publications 0269-8811 1461-7285 Original Papers, Ventral hippocampus, medial prefrontal cortex, venlafaxine, optogenetic stimulation, WKY rat 1 10 2021 2021-10-01 10.1177/02698811211048281 COLLEGE NANME Psychology School COLLEGE CODE PSYS Swansea University NCN grant no. 2017/25/B/NZ7/02710, Maj Institute of Pharmacology Polish Academy of Sciences supported the open access publication 2021-11-03T14:17:29.7257068 2021-10-18T15:12:54.7186446 Faculty of Medicine, Health and Life Sciences School of Psychology Mariusz Papp 1 Piotr Gruca 2 Magdalena Lason 3 Ewa Litwa 4 Wojciech Solecki 5 Paul Willner 6 58386__21208__0b49b3a1894f4d03999031b181fa47bb.pdf 10.1177_02698811211048281.pdf 2021-10-18T15:12:54.7183863 Output 999698 application/pdf Version of Record true This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License true eng https://creativecommons.org/licenses/by-nc/4.0/
title Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response
spellingShingle Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response
Paul Willner
title_short Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response
title_full Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response
title_fullStr Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response
title_full_unstemmed Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response
title_sort Insufficiency of ventral hippocampus to medial prefrontal cortex transmission explains antidepressant non-response
author_id_str_mv 4c278ffb6e4af6ab8816be40af66ecd3
author_id_fullname_str_mv 4c278ffb6e4af6ab8816be40af66ecd3_***_Paul Willner
author Paul Willner
author2 Mariusz Papp
Piotr Gruca
Magdalena Lason
Ewa Litwa
Wojciech Solecki
Paul Willner
format Journal article
container_title Journal of Psychopharmacology
container_volume 35
container_issue 10
container_start_page 1253
publishDate 2021
institution Swansea University
issn 0269-8811
1461-7285
doi_str_mv 10.1177/02698811211048281
publisher SAGE Publications
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str School of Psychology{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}School of Psychology
document_store_str 1
active_str 0
description Background:: There is extensive evidence that antidepressant drugs restore normal brain function by repairing damage to ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). While the damage is more extensive in hippocampus, the evidence of treatments, such as deep brain stimulation, suggests that functional changes in prefrontal cortex may be more critical. We hypothesized that antidepressant non-response may result from an insufficiency of transmission from vHPC to mPFC. Method:: Antidepressant non-responsive Wistar Kyoto (WKY) rats were subjected to chronic mild stress (CMS), then treated with chronic daily administration of the antidepressant drug venlafaxine (VEN) and/or repeated weekly optogenetic stimulation (OGS) of afferents to mPFC originating from vHPC or dorsal HPC (dHPC). Results:: As in many previous studies, CMS decreased sucrose intake, open-arm entries on the elevated plus maze (EPM), and novel object recognition (NOR). Neither VEN nor vHPC–mPFC OGS alone was effective in reversing the effects of CMS, but the combination of chronic VEN and repeated OGS restored normal behaviour on all three measures. dHPC–mPFC OGS restored normal behaviour in the EPM and NOR test irrespective of concomitant VEN treatment, and had no effect on sucrose intake. Conclusions:: The synergism between VEN and vHPC–mPFC OGS supports the hypothesis that the antidepressant non-responsiveness of WKY rats results from a failure of antidepressant treatment fully to restore transmission in the vHPC–mPFC pathway.
published_date 2021-10-01T05:19:49Z
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score 11.2862625

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