Proteomic analysis of rat hippocampus exposed to the antidepressant paroxetine
Abstract
Antidepressant drugs can exert significant effects on the mood of a patient suffering major depression and other disorders. These drugs generally have pharmacological actions on the uptake or metabolism of the neurotransmitters serotonin, noradrenaline and, to a lesser extent, dopamine. However, there are many aspects of antidepressant action we do not understand. We have applied proteomic analysis in a rat hippocampal model in an attempt to identify relevant molecules that operate in pathways functionally relevant to antidepressant action. Rats were administered either 5 mg/kg daily of the antidepressant paroxetine or vehicle for 12 days, then hippocampal protein was recovered and resolved by 2-D gel electrophoresis. After antidepressant exposure, we observed increased expression or modification of cytochrome c oxidase, subunit Va, cyclin-dependent kinase inhibitor 2A interacting protein, dynein, axonemal, heavy polypeptide 3 and RHO GDP-dissociation inhibitor alpha. Decreased expression or modification was observed for complexin 1 (CPLX1), alpha-synuclein, parvalbumin, ribosomal protein large P2, prohibitin, nerve growth factor, beta subunit (NGFB), peroxiredoxin 6 (PRDX6), 1-acylglycerol-3-phosphate O-acyltransferase 2_predicted, cystatin B (CYTB) and lysosomal membrane glycoprotein 1. CPLX1, the most strongly regulated protein observed, mediates the fusion of cellular transport vesicles with their target membranes and has been implicated in the pathophysiology of mood disorders, as well as antidepressant action. CPLX1 and the other proteins identified may represent links into molecular processes of importance to mood dysregulation and control, and their respective genes may represent novel candidates for studies of antidepressant pharmacogenetics.
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PRDX6 has been linked to depressive and anxiety-like behavior in mice as well as to paroxetine, escitalopram, and sertraline administration in rats.
“PRDX6 has been linked to depressive (Gu et al., 2022) and anxiety-like (Pairojana et al., 2022) behavior in mice as well as to paroxetine (McHugh et al., 2010), escitalopram, and sertraline (Bisgaard et al., 2012) administration in rats.”
From Epigenome-wide DNA methylation in unipolar depression: predictive biomarker of antidepressant treatment response? (2024) · cites this paper as McHugh et al., 2010
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- Authors
- McHugh, P., Rogers, G., Glubb, D., Joyce, P., & Kennedy, M.
- Affiliations
- Department of Pathology, University of Otago, Christchurch, New Zealand,
- University of Otago (NZ)
- Department of Pathology, University of Otago, Christchurch, New Zealand
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2009-04-03
- Volume
- 24
- Issue
- 8
- Pages
- 1243-1251
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2168498323
- Cited by
- 25
- References
- 71
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2016: 1 · 2014: 3 · 2013: 1 · 2012: 3
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- University of Huddersfield Repository (University of Huddersfield) (submittedVersion)
- Funders
- Canterbury Medical Research Foundation
- Fondation pour la Recherche Médicale
- Lotto New Zealand
- Health Research Council of New Zealand
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- paroxetine, antidepressant action, hippocampus, proteomics, complexin-1, mood disorders, serotonin, neurotransmitter uptake, protein expression changes
- MeSH terms
- Animals, Depression, Disease Models, Animal, Hippocampus, Image Processing, Computer-Assisted, Male, Proteins, Electrophoresis, Gel, Two-Dimensional, Rats, Sprague-Dawley, Paroxetine, Antidepressive Agents, Second-Generation, Proteomics, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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