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

Research output: Contribution to journal › Journal article › Research › peer-review

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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 T., Jesper; Olsen, G M; Wiborg, O; Redrobe, J P.

In: Journal of Psychopharmacology, Vol. 23, No. 7, 01.09.2009, p. 797-804.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Andreasen T., J, Olsen, GM, Wiborg, O & Redrobe, JP 2009, 'Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests', Journal of Psychopharmacology, vol. 23, no. 7, pp. 797-804. https://doi.org/10.1177/0269881108091587

APA

Andreasen T., J., Olsen, G. M., Wiborg, O., & Redrobe, J. P. (2009). Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests. Journal of Psychopharmacology, 23(7), 797-804. https://doi.org/10.1177/0269881108091587

Vancouver

Andreasen T. J, Olsen GM, Wiborg O, Redrobe JP. Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests. Journal of Psychopharmacology. 2009 Sep 1;23(7):797-804. https://doi.org/10.1177/0269881108091587

Author

Andreasen T., Jesper ; Olsen, G M ; Wiborg, O ; Redrobe, J P. / Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests. In: Journal of Psychopharmacology. 2009 ; Vol. 23, No. 7. pp. 797-804.

Bibtex

@article{cf90c0e8c6744fcb917eb1930f02015d,
title = "Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests",
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 (alpha4beta2-selective agonist), PNU-282987 (alpha7-selective agonist), mecamylamine (non-selective antagonist), dihydro-beta-erythroidine (DHbetaE; alpha4beta2-selective antagonist), methyllycaconitine (MLA; alpha7-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 alpha4beta2 or alpha7 nAChRs with DHbetaE 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 alpha4beta2 and/or alpha7 nAChRs induced antidepressant-like effects in mice. A strategy involving antagonism of central nAChRs could potentially lead to the development of novel antidepressant therapeutics.",
keywords = "Animals, Antidepressive Agents, Behavior, Animal, Citalopram, Depression, Disease Models, Animal, Female, Mice, Mice, Inbred Strains, Morpholines, Motor Activity, Nicotinic Agonists, Nicotinic Antagonists",
author = "{Andreasen T.}, Jesper and Olsen, {G M} and O Wiborg and Redrobe, {J P}",
year = "2009",
month = sep,
day = "1",
doi = "10.1177/0269881108091587",
language = "English",
volume = "23",
pages = "797--804",
journal = "Journal of Psychopharmacology",
issn = "0269-8811",
publisher = "SAGE Publications",
number = "7",

}

RIS

TY - JOUR

T1 - Antidepressant-like effects of nicotinic acetylcholine receptor antagonists, but not agonists, in the mouse forced swim and mouse tail suspension tests

AU - Andreasen T., Jesper

AU - Olsen, G M

AU - Wiborg, O

AU - Redrobe, J P

PY - 2009/9/1

Y1 - 2009/9/1

N2 - 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 (alpha4beta2-selective agonist), PNU-282987 (alpha7-selective agonist), mecamylamine (non-selective antagonist), dihydro-beta-erythroidine (DHbetaE; alpha4beta2-selective antagonist), methyllycaconitine (MLA; alpha7-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 alpha4beta2 or alpha7 nAChRs with DHbetaE 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 alpha4beta2 and/or alpha7 nAChRs induced antidepressant-like effects in mice. A strategy involving antagonism of central nAChRs could potentially lead to the development of novel antidepressant therapeutics.

AB - 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 (alpha4beta2-selective agonist), PNU-282987 (alpha7-selective agonist), mecamylamine (non-selective antagonist), dihydro-beta-erythroidine (DHbetaE; alpha4beta2-selective antagonist), methyllycaconitine (MLA; alpha7-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 alpha4beta2 or alpha7 nAChRs with DHbetaE 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 alpha4beta2 and/or alpha7 nAChRs induced antidepressant-like effects in mice. A strategy involving antagonism of central nAChRs could potentially lead to the development of novel antidepressant therapeutics.

KW - Animals

KW - Antidepressive Agents

KW - Behavior, Animal

KW - Citalopram

KW - Depression

KW - Disease Models, Animal

KW - Female

KW - Mice

KW - Mice, Inbred Strains

KW - Morpholines

KW - Motor Activity

KW - Nicotinic Agonists

KW - Nicotinic Antagonists

U2 - 10.1177/0269881108091587

DO - 10.1177/0269881108091587

M3 - Journal article

C2 - 18583432

VL - 23

SP - 797

EP - 804

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

SN - 0269-8811

IS - 7

ER -

ID: 33879181