Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Y S MineurM R Picciotto

Abstract

Medications that target the noradrenergic system are important therapeutics for depression and anxiety disorders. More recently, clinical studies have shown that the α2-noradrenergic receptor (α2AR) agonist guanfacine can decrease stress-induced smoking relapse during acute abstinence, suggesting that targeting the noradrenergic system may aid in smoking cessation through effects on stress pathways in the brain. Acetylcholine (ACh), like the nicotine in tobacco, acts at nicotinic acetylcholine receptors (nAChRs) to regulate behaviors related to anxiety and depression. We therefore investigated interactions between guanfacine and ACh signaling in tests of anxiolytic and antidepressant efficacy in female and male C57BL/6J mice, focusing on the amygdala as a potential site of noradrenergic/cholinergic interaction. The antidepressant-like effects of guanfacine were blocked by shRNA-mediated knockdown of α2AR in amygdala. Knockdown of the high-affinity β2 nAChR subunit in amygdala also prevented antidepressant-like effects of guanfacine, suggesting that these behavioral effects require ACh signaling through β2-containing nAChRs in this brain area. Ablation of NE terminals prevented the anxiolytic- and antidepressant-like effects of ...Continue Reading

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Citations

May 21, 2019·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Susana Barbosa Méndez, Alberto Salazar-Juárez
Dec 11, 2019·The European Journal of Neuroscience·Yann S Mineur, Marina R Picciotto
Feb 9, 2020·Psychopharmacology·Stephen H Curry, Matthew Marler
Feb 20, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Rafael E PerezDanny G Winder
Jul 28, 2020·Translational Psychiatry·Paul J FitzgeraldBrendon O Watson
Aug 19, 2018·Molecular Psychiatry·Stephanie C Dulawa, David S Janowsky
Apr 29, 2021·Behavioural Brain Research·Paul J FitzgeraldBrendon O Watson
Apr 29, 2020·Cold Spring Harbor Perspectives in Medicine·Marina R Picciotto, Paul J Kenny
May 31, 2021·Clinical Neurology and Neurosurgery·Paul J Fitzgerald
Jun 5, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Cecilia Gotti, Francesco Clementi
Aug 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·María Abellán-ÁlvaroEnrique Lanuza
Jan 8, 2022·Medicinal Research Reviews·Kristina RepovaFedor Simko

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Methods Mentioned

BETA
transfection
PCR

Software Mentioned

BLAST
REST

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