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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Modulation of aggressive behavior in mice by nicotinic receptor subtypes
Biochemical pharmacology, v 97(4), pp 488-497
15 Oct 2015
PMID: 26212554
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Aggression is frequently comorbid with neuropsychiatric conditions and is a predictor of worse outcomes, yet current pharmacotherapies are insufficient and have debilitating side effects, precluding broad use. Multiple models of aggression across species suggest that the nicotinic acetylcholine receptor (nAChR) agonist nicotine has anti-aggressive (serenic) properties. Here we demonstrate dose-dependent serenic effects of acute nicotine administration in three distinct mouse strains: C57BL/6, BALB/c, and CD1. While acute nicotine administration (0.25 mg/kg) modestly reduced solitary homecage locomotion, this could not account for nicotine's serenic effects since social encounters eliminated the hypolocomotor effect, and nicotine did not alter social interaction times. Pretreatment with the homomeric (alpha 7 subunit) nAChR antagonist methyllycaconitine (5 mg/kg), but not the heteromeric (beta 2 or beta 4 subunit-containing) nAChR antagonist dihydro-beta-erythroidine (DH beta E, 3 mg/kg), blocked the serenic effects of nicotine. By contrast, pretreatment with DH beta E blocked the effect of acute nicotine administration on locomotion, uncoupling nicotine's serenic and hypolocomotor effects. Finally, the alpha 7 nAChR partial agonist GTS-21 reduced aggression in C57BL/6 mice. These results support the idea that acute nicotine administration has serenic effects and provide evidence for specificity of this effect distinct from effects on locomotion. Furthermore, pharmacological studies suggest that activation of alpha 7 nAChRs underlies the serenic effects of nicotine. Further studies of nAChRs could enhance understanding of the neurobiology of aggression and may lead to the development of novel, more specific treatments for pathological aggression. (C) 2015 Elsevier Inc. All rights reserved.
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Details
- Title
- Modulation of aggressive behavior in mice by nicotinic receptor subtypes
- Creators
- Alan S. Lewis - Yale UniversityYann S. Mineur - Yale UniversityPhilip H. Smith - Yale UniversityEmma L. M. Cahuzac - Yale UniversityMarina R. Picciotto - Yale University
- Publication Details
- Biochemical pharmacology, v 97(4), pp 488-497
- Publisher
- Elsevier
- Number of pages
- 10
- Grant note
- MH19961; MH014276; DA14241; MH077681 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01DA014241 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission R25MH071584 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000363437200016
- Scopus ID
- 2-s2.0-84943350610
- Other Identifier
- 991022030932704721
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- Web of Science research areas
- Pharmacology & Pharmacy