Affordable Access

deepdyve-link
Publisher Website

Nicotine improves probabilistic reward learning in wildtype but not alpha7 nAChR null mutants, yet alpha7 nAChR agonists do not improve probabilistic learning.

Authors
  • Milienne-Petiot, Morgane1
  • Higa, Kerin K2
  • Grim, Andrea2
  • Deben, Debbie1
  • Groenink, Lucianne2
  • Twamley, Elizabeth W3
  • Geyer, Mark A4
  • Young, Jared W5
  • 1 Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, MC 0804, La Jolla, CA 92093-0804, United States; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands. , (Netherlands)
  • 2 Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, MC 0804, La Jolla, CA 92093-0804, United States. , (United States)
  • 3 Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, MC 0804, La Jolla, CA 92093-0804, United States; Center of Excellence for Stress and Mental Health and Research Service, VA San Diego Healthcare System, United States. , (United States)
  • 4 Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, MC 0804, La Jolla, CA 92093-0804, United States; Research Service, VA San Diego Healthcare System, San Diego, CA, United States. , (United States)
  • 5 Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, MC 0804, La Jolla, CA 92093-0804, United States; Research Service, VA San Diego Healthcare System, San Diego, CA, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
Publication Date
Nov 01, 2018
Volume
28
Issue
11
Pages
1217–1231
Identifiers
DOI: 10.1016/j.euroneuro.2018.08.005
PMID: 30213668
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Cognitive impairments, e.g., reward learning, are present in various psychiatric disorders and warrant treatment. Improving reward-related learning could synergistically enhance psychosocial treatments and cognition generally. A critical first step is to understand the mechanisms underlying reward learning. The dopamine system has been implicated in such learning, but less known is how indirect activation of this system may affect reward learning. We determined the role of alpha7 nicotinic acetylcholine receptors (nAChR) on a probabilistic reversal learning task (PRLT) in mice that includes reward and punishment. Male alpha7 knockout (KO), heterozygous (HT), and wildtype (WT) littermate mice (n = 84) were treated with vehicle, 0.03, or 0.3 mg/kg nicotine. Two cohorts of C57BL/6NJ male mice were treated with various alpha7 nAChR ligands, including the full agonists PNU282877 and AR-R-17779, the positive allosteric modulator CCMI, the partial agonist SSR180711, and the antagonist methyllycaconitine. All mice were then tested in the PRLT. Nicotine (0.3 mg/kg) significantly improved initial reward learning in alpha7 WT and HT mice but did not improve learning in KO mice, suggesting an involvement of the alpha7 nAChR in the pro-learning effects of nicotine. Neither alpha7 nAChR treatments (PNU282987, AR-R-17779, CCMI, SSR180711, nor methyllycaconitine) affected mouse PRLT performance however. Nicotine improved reward learning via a mechanism that may include alpha7 nAChRs. This improvement unlikely relied solely on alpha7 nAChRs however, since no alpha7 nAChR ligand improved reward learning in normal mice. Future assessments of the effects of other nAChR subtypes on reward learning are needed. Copyright © 2018 Elsevier B.V. and European College of Neuropsychopharmacology. All rights reserved.

Report this publication

Statistics

Seen <100 times