A novel butyrylcholinesterase inhibitor induces antidepressant, pro-cognitive, and anti-anhedonic effects in Flinders Sensitive Line rats: The role of the ghrelin-dopamine cascade
FSL rats display impaired ghrelin, DA, serotonin, growth hormone, and BDNF signalling, akin to MDD. BChEI exerts antidepressant-like effects across despair, reward, and cognitive domains, most likely via the BChE-ghrelin-DA cascade. Reversal of these effects by ghrelin antagonism underscores the critical role of ghrelin, specifically via growth hormone secretagogue receptor-ghrelin interaction. These findings suggest a potentially novel multimodal neurobiological target for the treatment of MDD.
Authors
- Stanislav Gobec (ORCID: https://orcid.org/0000-0002-9678-3083)
- Brian H. Harvey (ORCID: https://orcid.org/0000-0002-9864-7894)
- Simon Žakelj (ORCID: https://orcid.org/0000-0002-4967-7114)
- C. Brink (ORCID: https://orcid.org/0000-0003-2707-1258)
- Urban Košak (ORCID: https://orcid.org/0000-0001-7537-0362)
- Mohammed Shahid
- Nathalie Olivier
Institutions
- South African Medical Research Council (ZA)
- University of Ljubljana (SI)
- North-West University (ZA)
- R-Biopharm (United Kingdom) (GB)
Publication Details
- Journal
- Biomedicine & Pharmacotherapy
- Published
- 2025-05-02
- DOI
- https://doi.org/10.1016/j.biopha.2025.118093
- Citations
- 6
- Primary Topic
- Cholinesterase and Neurodegenerative Diseases
- Type
- article
- Field-Weighted Citation Impact
- 8.37
Funders
- South African Medical Research Council
- Council of Scientific and Industrial Research, India
- Javna Agencija za Raziskovalno Dejavnost RS