MUNC13-1 heterozygosity does not alter voluntary ethanol consumption or sensitivity in mice.
Addiction
Anxiety
Cognition
Spatial learning
Tolerance
Journal
Alcohol (Fayetteville, N.Y.)
ISSN: 1873-6823
Titre abrégé: Alcohol
Pays: United States
ID NLM: 8502311
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
12
02
2019
revised:
12
06
2019
accepted:
21
06
2019
pubmed:
3
7
2019
medline:
9
1
2021
entrez:
3
7
2019
Statut:
ppublish
Résumé
The role of the munc13-1 presynaptic protein in alcohol-related behaviors has been little-studied, despite being a known site of action for ethanol binding. Munc13-1 is an active zone protein that plays a vital role in vesicle maturation and the release of neurotransmitters in excitatory neurons. Ethanol binds munc13-1, which decreases its functionality. In Drosophila, loss of the homologous protein Dunc13 is associated with an increase in ethanol preference, and is associated with a resistance to sedation following ethanol exposure. The current study assessed the effects of munc13-1 heterozygosity on ethanol sensitivity and consumption in mice, as well as on learning and anxiety-like behaviors, which can influence alcohol intake. Wild-type and mutant mice underwent 6 cycles of drinking-in-the-dark (DID) as well as rotarod testing following ethanol injection, to probe for differences in ethanol consumption and sensitivity, respectively. We did not detect genotype-based differences in our measures of anxiety, spatial learning, ethanol consumption, or ethanol sensitivity. However, heterozygotes showed increased use of a spatial navigation strategy in a dual-solution water maze, as opposed to a stimulus-response strategy. To summarize, although reduction of Dunc13 in flies produces clear effects on ethanol consumption and sensitivity, heterozygosity for munc13-1 does not, potentially due to compensatory adaptation by other munc-13 isoforms.
Identifiants
pubmed: 31265903
pii: S0741-8329(19)30013-8
doi: 10.1016/j.alcohol.2019.06.007
pmc: PMC7043798
mid: NIHMS1552684
pii:
doi:
Substances chimiques
Nerve Tissue Proteins
0
Unc13a protein, mouse
0
Ethanol
3K9958V90M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-97Subventions
Organisme : NIAAA NIH HHS
ID : R01 AA022414
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Références
Alcohol. 2008 May;42(3):149-60
pubmed: 18358676
J Physiol. 2004 May 15;557(Pt 1):147-57
pubmed: 15034127
Neuropharmacology. 2017 Sep 1;123:201-209
pubmed: 28623169
Genes Brain Behav. 2007 Feb;6(1):1-18
pubmed: 17233637
Eur Addict Res. 2007;13(1):39-49
pubmed: 17172778
Brain Res Bull. 1998 Jul 15;46(5):441-5
pubmed: 9739007
Behav Neurosci. 1992 Jun;106(3):439-46
pubmed: 1616610
Physiol Rev. 1997 Jan;77(1):1-20
pubmed: 9016298
eNeuro. 2018 Jun 8;5(3):
pubmed: 29911175
J Vis Exp. 2013 May 29;(75):e2609
pubmed: 23748408
J Neurosci. 2004 Aug 4;24(31):6979-85
pubmed: 15295033
Alcohol. 2003 Apr;29(3):165-71
pubmed: 12798972
J Pharmacol Pharmacother. 2011 Jul;2(3):214-5
pubmed: 21897729
Biomolecules. 2015 Aug 17;5(3):1870-911
pubmed: 26287261
Brain Res Brain Res Rev. 1993 Jan-Apr;18(1):33-49
pubmed: 8467349
Behav Neurosci. 1996 Dec;110(6):1309-20
pubmed: 8986334
J Biol Chem. 1997 Jan 24;272(4):2520-6
pubmed: 8999968
Alcohol Clin Exp Res. 1999 Oct;23(10):1563-70
pubmed: 10549986
Psychopharmacology (Berl). 1993;112(4):503-10
pubmed: 7871064
Brain Res Bull. 2000 Jul 1;52(4):243-8
pubmed: 10856821
Neuron. 2012 Jul 12;75(1):11-25
pubmed: 22794257
Physiol Behav. 2005 Jan 31;84(1):53-63
pubmed: 15642607
Curr Opin Neurobiol. 2003 Oct;13(5):509-19
pubmed: 14630212
J Neurochem. 2013 Sep;126(6):715-26
pubmed: 23692447
Alcohol. 2007 Nov;41(7):517-24
pubmed: 17980788
Biochem J. 1999 Feb 1;337 ( Pt 3):363-71
pubmed: 9895278
J Biol Chem. 2006 Jul 14;281(28):19720-31
pubmed: 16704978
Science. 2011 Jul 15;333(6040):353-7
pubmed: 21764750
Genetics. 1974 May;77(1):71-94
pubmed: 4366476
Physiol Behav. 2012 Feb 28;105(4):1014-20
pubmed: 22146478
Behav Brain Res. 2006 Aug 10;171(2):216-24
pubmed: 16647766
Neurobiol Learn Mem. 2004 Sep;82(2):142-9
pubmed: 15341799
Trends Pharmacol Sci. 2003 Sep;24(9):456-60
pubmed: 12967770
Neurobiol Learn Mem. 2008 Oct;90(3):553-9
pubmed: 18644245
Alcohol. 2014 May;48(3):235-41
pubmed: 24275142
Nature. 1999 Jul 29;400(6743):457-61
pubmed: 10440375
Neuron. 2017 Aug 2;95(3):473-475
pubmed: 28772115
Behav Neural Biol. 1994 May;61(3):260-70
pubmed: 8067981
Neuropharmacology. 2017 Aug 1;122:46-55
pubmed: 28341206
Hippocampus. 2017 Aug;27(8):871-882
pubmed: 28474795
Psychopharmacologia. 1975 Sep 17;43(3):245-54
pubmed: 1237914
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2917-22
pubmed: 12584362
J Cogn Neurosci. 2008 Mar;20(3):432-46
pubmed: 18004952