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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
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, 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.
Keywords: Original Papers, Ventral hippocampus, medial prefrontal cortex, venlafaxine, optogenetic stimulation, WKY rat
College: Faculty of Medicine, Health and Life Sciences
Funders: NCN grant no. 2017/25/B/NZ7/02710, Maj Institute of Pharmacology Polish Academy of Sciences supported the open access publication
Issue: 10
Start Page: 1253
End Page: 1264

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