N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
31 07 2023
31 07 2023
Historique:
received:
22
01
2023
accepted:
25
07
2023
revised:
19
07
2023
medline:
3
8
2023
pubmed:
1
8
2023
entrez:
31
7
2023
Statut:
epublish
Résumé
The endocannabinoid system (ECS) plays a key modulatory role during synaptic plasticity and homeostatic processes in the brain and has an important role in the neurobiological processes underlying drug addiction. We have previously shown that an elevated ECS response to psychostimulant (cocaine) is involved in regulating the development and expression of cocaine-conditioned reward and sensitization. We therefore hypothesized that drug-induced elevation in endocannabinoids (eCBs) and/or eCB-like molecules (eCB-Ls) may represent a protective mechanism against drug insult, and boosting their levels exogenously may strengthen their neuroprotective effects. Here, we determine the involvement of ECS in alcohol addiction. We first measured the eCBs and eCB-Ls levels in different brain reward system regions following chronic alcohol self-administration using LC-MS. We have found that following chronic intermittent alcohol consumption, N-oleoyl glycine (OlGly) levels were significantly elevated in the prefrontal cortex (PFC), and N-oleoyl alanine (OlAla) was significantly elevated in the PFC, nucleus accumbens (NAc) and ventral tegmental area (VTA) in a region-specific manner. We next tested whether exogenous administration of OlGly or OlAla would attenuate alcohol consumption and preference. We found that systemic administration of OlGly or OlAla (60 mg/kg, intraperitoneal) during intermittent alcohol consumption significantly reduced alcohol intake and preference without affecting the hedonic state. These findings suggest that the ECS negatively regulates alcohol consumption and boosting selective eCBs exogenously has beneficial effects against alcohol consumption and potentially in preventing relapse.
Identifiants
pubmed: 37524707
doi: 10.1038/s41398-023-02574-4
pii: 10.1038/s41398-023-02574-4
pmc: PMC10390512
doi:
Substances chimiques
Glycine
TE7660XO1C
Ethanol
3K9958V90M
Cocaine
I5Y540LHVR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
273Informations de copyright
© 2023. The Author(s).
Références
Alcohol Clin Exp Res. 1980 Apr;4(2):190-8
pubmed: 6990822
Alcohol Clin Exp Res. 2008 Oct;32(10):1714-20
pubmed: 18627359
Psychopharmacologia. 1973;29(3):203-10
pubmed: 4702273
Br J Pharmacol. 2004 Oct;143(4):455-64
pubmed: 15371286
Alcohol Clin Exp Res. 2008 Oct;32(10):1816-23
pubmed: 18671810
Alcohol. 1999 Apr;17(3):175-83
pubmed: 10231165
Neuropsychopharmacology. 2007 Jul;32(7):1570-82
pubmed: 17164820
Br J Pharmacol. 2011 Aug;163(7):1402-10
pubmed: 21418185
Curr Opin Chem Biol. 2009 Jun;13(3):321-31
pubmed: 19497779
Neuropharmacology. 2019 Apr;148:320-331
pubmed: 29567093
J Neurosci. 2008 Dec 17;28(51):13985-94
pubmed: 19091987
Sci STKE. 2002 Apr 23;2002(129):re5
pubmed: 11972360
Cannabis Cannabinoid Res. 2022 May 31;:
pubmed: 35647907
Vitam Horm. 2009;81:191-205
pubmed: 19647113
Science. 2002 Apr 26;296(5568):678-82
pubmed: 11976437
Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8114-9
pubmed: 18541917
Front Cell Neurosci. 2014 Aug 01;8:195
pubmed: 25136293
Curr Top Behav Neurosci. 2011;8:73-96
pubmed: 21769724
Biol Psychiatry. 2022 Dec 7;:
pubmed: 36868890
Neuropsychopharmacology. 2019 Jan;44(2):415-424
pubmed: 30008470
Molecules. 2019 Mar 21;24(6):
pubmed: 30901889
Nat Rev Neurol. 2020 Jan;16(1):9-29
pubmed: 31831863
Transl Psychiatry. 2013 Feb 19;3:e231
pubmed: 23423140
Prog Neurobiol. 1998 Nov;56(4):385-431
pubmed: 9775400
Neuropsychopharmacology. 2010 Jan;35(1):217-38
pubmed: 19710631
J Med Chem. 1994 Jun 10;37(12):1889-93
pubmed: 8021930
J Pharmacol Exp Ther. 1993 Apr;265(1):218-26
pubmed: 8474008
Front Aging Neurosci. 2022 Oct 14;14:926634
pubmed: 36313013
ACS Chem Neurosci. 2018 Sep 19;9(9):2146-2161
pubmed: 29400439
J Med Chem. 1997 Feb 28;40(5):659-67
pubmed: 9057852
Cell Metab. 2019 Jun 4;29(6):1320-1333.e8
pubmed: 31105045
Psychopharmacology (Berl). 2019 Sep;236(9):2623-2633
pubmed: 30993360
Neuropharmacology. 2019 Mar 1;146:184-197
pubmed: 30496754
J Neurosci. 1991 Feb;11(2):563-83
pubmed: 1992016
J Neurochem. 2008 Sep;106(6):2322-36
pubmed: 18643796
Nat Rev Neurosci. 2015 Oct;16(10):579-94
pubmed: 26373473
Dialogues Clin Neurosci. 2020 Sep;22(3):241-250
pubmed: 33162767
Neurotherapeutics. 2017 Jul;14(3):687-697
pubmed: 28324454
Psychopharmacology (Berl). 2020 Sep;237(9):2753-2765
pubmed: 32556401
Arch Gen Psychiatry. 1983 Apr;40(4):435-42
pubmed: 6838323
Proc Nutr Soc. 2014 Feb;73(1):96-105
pubmed: 24135210
Addict Biol. 2016 Jul;21(4):859-72
pubmed: 26037332
Cells. 2021 Mar 07;10(3):
pubmed: 33799988
Alcohol Clin Exp Res. 2003 Feb;27(2):232-43
pubmed: 12605072
ACS Chem Neurosci. 2020 Apr 15;11(8):1117-1128
pubmed: 32017529
J Neurochem. 2001 Sep;78(6):1415-27
pubmed: 11579150