COX-2 Inhibition Antagonizes Intra-Accumbens 2-Arachidonoylglycerol-Mediated Reduction in Ethanol Self-Administration in Rats.
Alcohol Drinking
/ drug therapy
Animals
Arachidonic Acids
/ antagonists & inhibitors
Biphenyl Compounds
/ pharmacology
Cyclooxygenase 2 Inhibitors
/ pharmacology
Dose-Response Relationship, Drug
Endocannabinoids
/ antagonists & inhibitors
Glycerides
/ antagonists & inhibitors
Male
Nucleus Accumbens
/ drug effects
Polyunsaturated Alkamides
/ pharmacology
Rats
Rats, Wistar
Receptor, Cannabinoid, CB1
/ drug effects
Rimonabant
/ pharmacology
Self Administration
Sulfonamides
/ pharmacology
2-Arachidonoyl Glycerol
Cyclooxygenase-2
Ethanol
Nucleus Accumbens
Journal
Alcoholism, clinical and experimental research
ISSN: 1530-0277
Titre abrégé: Alcohol Clin Exp Res
Pays: England
ID NLM: 7707242
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
19
03
2020
accepted:
01
09
2020
pubmed:
19
9
2020
medline:
9
9
2021
entrez:
18
9
2020
Statut:
ppublish
Résumé
Ethanol (EtOH) self-administration is particularly sensitive to the modulation of CB In order to further explore this hypothesis, we analyzed the alterations in operant EtOH self-administration induced by intra-NAc shell infusions of 2-AG itself, the CB Surprisingly, self-administration of 10% EtOH was dose-dependently reduced by either intra-NAc shell SR141716A or 2-AG infusions. Similar effects were found by intra-NAc shell infusions of URB602, suggesting again a role for accumbal 2-AG on the modulation of EtOH intake. Intra-NAc shell anandamide did not alter EtOH self-administration, pointing to a specific role for 2-AG in the modulation of EtOH self-administration. Finally, the inhibitory effect of intra-NAc shell 2-AG on EtOH intake was significantly reversed by pretreatment with nimesulide, suggesting that oxidative metabolites of 2-AG might mediate these inhibitory effects on operant self-administration. We propose that 2-AG signaling in the NAc exerts an inhibitory influence on EtOH consumption through a non-CB1 receptor mechanism involving the COX-2 pathway.
Sections du résumé
BACKGROUND
Ethanol (EtOH) self-administration is particularly sensitive to the modulation of CB
METHODS
In order to further explore this hypothesis, we analyzed the alterations in operant EtOH self-administration induced by intra-NAc shell infusions of 2-AG itself, the CB
RESULTS
Surprisingly, self-administration of 10% EtOH was dose-dependently reduced by either intra-NAc shell SR141716A or 2-AG infusions. Similar effects were found by intra-NAc shell infusions of URB602, suggesting again a role for accumbal 2-AG on the modulation of EtOH intake. Intra-NAc shell anandamide did not alter EtOH self-administration, pointing to a specific role for 2-AG in the modulation of EtOH self-administration. Finally, the inhibitory effect of intra-NAc shell 2-AG on EtOH intake was significantly reversed by pretreatment with nimesulide, suggesting that oxidative metabolites of 2-AG might mediate these inhibitory effects on operant self-administration.
CONCLUSIONS
We propose that 2-AG signaling in the NAc exerts an inhibitory influence on EtOH consumption through a non-CB1 receptor mechanism involving the COX-2 pathway.
Identifiants
pubmed: 32944989
doi: 10.1111/acer.14456
pmc: PMC7680444
mid: NIHMS1643678
doi:
Substances chimiques
Arachidonic Acids
0
Biphenyl Compounds
0
Cyclooxygenase 2 Inhibitors
0
Endocannabinoids
0
Glycerides
0
Polyunsaturated Alkamides
0
Receptor, Cannabinoid, CB1
0
Sulfonamides
0
URB602
0
glyceryl 2-arachidonate
8D239QDW64
Rimonabant
RML78EN3XE
anandamide
UR5G69TJKH
nimesulide
V4TKW1454M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2158-2165Subventions
Organisme : NIAAA NIH HHS
ID : R37 AA017447
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA022249
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA017447
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA006420
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA020404
Pays : United States
Organisme : NIAAA NIH HHS
ID : P60 AA006420
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026999
Pays : United States
Informations de copyright
© 2020 by the Research Society on Alcoholism.
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