α4β2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties

Yann S Mineur; Emily B Einstein; Patricia A Seymour; Jotham W Coe; Brian T O’Neill; Hans Rollema; Marina R Picciotto

doi:10.1097/FBP.0b013e328347546d

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α4β2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties

Journal article

Peer reviewed

α4β2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties

Yann S Mineur, Emily B Einstein, Patricia A Seymour, Jotham W Coe, Brian T O’Neill, Hans Rollema and Marina R Picciotto

Behavioural pharmacology, Vol.22(4), pp.291-299

08/2011

DOI: 10.1097/FBP.0b013e328347546d

PMCID: PMC3227135

PMID: 21566524

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https://www.ncbi.nlm.nih.gov/pmc/articles/3227135View

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Abstract

Previous studies have suggested that treatment with antagonists or partial agonists of nicotinic acetylcholine receptors containing the β2 subunit (β2* nAChRs) results in antidepressant-like effects. In the current study we tested 3 novel compounds with different affinity and functional efficacy at α4β2* nAChRs, which were synthesized as part of nAChR discovery projects at Pfizer in the tail suspension, forced swim and novelty-suppressed feeding tests of antidepressant efficacy. All compounds tested reduced immobility in the forced swim test and one of the compounds also reduced immobility in the tail suspension test. All the compounds appeared to affect food intake on their own, with 2 compounds reducing feeding significantly in the home cage, precluding a clear interpretation of the results in the novelty-suppressed feeding test. None of the compounds altered locomotor activity at the doses and time points used here. Therefore, a subset of these compounds has pharmacological and behavioral properties that demonstrate the potential of nicotinic compounds as a treatment of mood disorders. Further development of nicotinic-based antidepressants should focus on increasing nAChR subtype selectivity to obtain consistent antidepressant properties with an acceptable side effect profile.

tail suspension test

Nicotinic acetylcholine receptors

depression

novelty-suppressed feeding

mice

partial agonists

forced swim test

Details

Title: Subtitle: α4β2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties
Creators: Yann S Mineur - Yale University School of Medicine, Dept of Psychiatry, Interdepartmental Neuroscience Program, 34 Park Street, New Haven, CT, 06508
Emily B Einstein - Yale University School of Medicine, Dept of Psychiatry, Interdepartmental Neuroscience Program, 34 Park Street, New Haven, CT, 06508
Patricia A Seymour - Dept. Neuroscience, Pfizer Global Research and Development, Groton, CT 06340
Jotham W Coe - Dept. Neuroscience, Pfizer Global Research and Development, Groton, CT 06340
Brian T O’Neill - Dept. Neuroscience, Pfizer Global Research and Development, Groton, CT 06340
Hans Rollema - Dept. Neuroscience, Pfizer Global Research and Development, Groton, CT 06340
Marina R Picciotto - Yale University School of Medicine, Dept of Psychiatry, Interdepartmental Neuroscience Program, 34 Park Street, New Haven, CT, 06508
Resource Type: Journal article
Publication Details: Behavioural pharmacology, Vol.22(4), pp.291-299
DOI: 10.1097/FBP.0b013e328347546d
PMID: 21566524
PMCID: PMC3227135
NLM abbreviation: Behav Pharmacol
ISSN: 0955-8810
eISSN: 1473-5849
Grant note: R01 MH077681-07 || MH / National Institute of Mental Health : NIMH K02 DA000436-10 || DA / National Institute on Drug Abuse : NIDA
Language: English
Date published: 08/2011
Academic Unit: Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094364002771

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