Cited by 106Nicotinic Acetylcholine Receptors StudyTreatment of Major DepressionNeuroscience and Neuropharmacology Research

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Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests

Andreasen, JT, Olsen, GM, Wiborg, O, Redrobe, JP·2009·Journal of Psychopharmacology

DOI 10.1177/0269881108091587

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Abstract

Abstract Current literature suggests involvement of nicotinic acetylcholine receptors (nAChRs) in major depression. However, it is controversial whether the antidepressant-like effect of nAChR modulation is induced by activation, desensitization or inhibition of central nAChRs. In addition, the specific nAChR subtype/s involved remains unknown. In this study, we systematically compared the effects of non-selective and selective nicotinic agonists and antagonists in two different tests for antidepressant effects in mice: the tail suspension test and the forced swim test. Compounds: nicotine, RJR-2403 (α4β2-selective agonist), PNU-282987 (α7-selective agonist), mecamylamine (non-selective antagonist), dihydro-β-erythroidine (DHβE; α4β2-selective antagonist), methyllycaconitine (MLA; α7-selective antagonist) and hexamethonium (non-brain-penetrant non-selective antagonist). All compounds were tested in a locomotor activity paradigm to rule out non-specific stimulant effects. The data show that blockade of nAChRs with mecamylamine, or selective antagonism of α4β2 or α7 nAChRs with DHβE or MLA, respectively, has antidepressant-like effects. These effects were not confounded by motor stimulation. Hexamethonium did not show antidepressant-like activity, supporting the involvement of central nAChRs. At the dose levels tested, none of the nAChR agonists displayed antidepressant-like profiles. In conclusion, antagonism of central α4β2 and/or α7 nAChRs induced antidepressant-like effects in mice. A strategy involving antagonism of central nAChRs could potentially lead to the development of novel antidepressant therapeutics.

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Authors: Andreasen, J., Olsen, G., Wiborg, O., & Redrobe, J.
Affiliations: NeuroSearch (Denmark) (DK)
Department of Biological Psychiatry, Psychiatric Hospital, Aarhus, Denmark
Corresponding author: Andreasen, JT
ORCID: Wiborg, O
Venue: Journal of Psychopharmacology
Publisher: SAGE Publications
Published: 2008-06-26
Volume: 23
Issue: 7
Pages: 797-804
ISSN: 0269-8811 (ISSN-L)
1461-7285
DOI: 10.1177/0269881108091587
OpenAlex: W2140936957
Cited by: 101
References: 48
Citations by year: 2026: 5 · 2025: 2 · 2023: 5 · 2022: 1 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 9 · 2017: 2 · 2016: 1 · 2015: 9 · 2014: 8 · 2013: 7 · 2012: 7
FWCI: 3.83
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: nicotinic acetylcholine receptors, antidepressant-like effects, major depressive disorder, nAChR antagonists, nicotinic agonists, alpha4beta2 nAChR, alpha7 nAChR, mecamylamine, dihydro-beta-erythroidine, methyllycaconitine, nicotine, PNU-282987, forced swim test, tail suspension test, locomotor activity, central nervous system
MeSH terms: Reboxetine, Animals, Antidepressive Agents, Behavior, Animal, Depression, Disease Models, Animal, Female, Mice, Inbred Strains, Morpholines, Motor Activity, Citalopram, Nicotinic Agonists, Nicotinic Antagonists, Mice

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Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests

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