Effects of repeated lysergic acid diethylamide (LSD) on the mouse brain endocannabinoidome and gut microbiome.
5-hydroxytryptamine system
endocannabinoidome
gut microbiome
kynurenine
lysergic acid diethylamide
repeated
serotonergic system
sociability
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
revised:
06
10
2022
received:
03
06
2022
accepted:
07
10
2022
pubmed:
1
11
2022
medline:
25
2
2023
entrez:
31
10
2022
Statut:
ppublish
Résumé
Psychedelics elicit prosocial, antidepressant and anxiolytic effects via neuroplasticity, neurotransmission and neuro-immunomodulatory mechanisms. Whether psychedelics affect the brain endocannabinoid system and its extended version, the endocannabinoidome (eCBome) or the gut microbiome, remains unknown. Adult C57BL/6N male mice were administered lysergic acid diethylamide (LSD) or saline for 7 days. Sociability was assessed in the direct social interaction and three chambers tests. Prefrontal cortex and hippocampal endocannabinoids, endocannabinoid-like mediators and metabolites were quantified via high-pressure liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Neurotransmitter levels were assessed via HPLC-UV/fluorescence. Gut microbiome changes were investigated by 16S ribosomal DNA sequencing. LSD increased social preference and novelty and decreased hippocampal levels of the N-acylethanolamines N-linoleoylethanolamine (LEA), anandamide (N-arachidonoylethanolamine) and N-docosahexaenoylethanolamine (DHEA); the monoacylglycerol 1/2-docosahexaenoylglycerol (1/2-DHG); the prostaglandins D The prosocial effects elicited by repeated LSD administration are accompanied by alterations of hippocampal eCBome and kynurenine levels, and the composition of the gut microbiota. Modulation of the hippocampal eCBome and kynurenine pathway might represent a mechanism by which psychedelic compounds elicit prosocial effects and affect the gut microbiome.
Sections du résumé
BACKGROUND AND PURPOSE
Psychedelics elicit prosocial, antidepressant and anxiolytic effects via neuroplasticity, neurotransmission and neuro-immunomodulatory mechanisms. Whether psychedelics affect the brain endocannabinoid system and its extended version, the endocannabinoidome (eCBome) or the gut microbiome, remains unknown.
EXPERIMENTAL APPROACH
Adult C57BL/6N male mice were administered lysergic acid diethylamide (LSD) or saline for 7 days. Sociability was assessed in the direct social interaction and three chambers tests. Prefrontal cortex and hippocampal endocannabinoids, endocannabinoid-like mediators and metabolites were quantified via high-pressure liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Neurotransmitter levels were assessed via HPLC-UV/fluorescence. Gut microbiome changes were investigated by 16S ribosomal DNA sequencing.
KEY RESULTS
LSD increased social preference and novelty and decreased hippocampal levels of the N-acylethanolamines N-linoleoylethanolamine (LEA), anandamide (N-arachidonoylethanolamine) and N-docosahexaenoylethanolamine (DHEA); the monoacylglycerol 1/2-docosahexaenoylglycerol (1/2-DHG); the prostaglandins D
CONCLUSIONS AND IMPLICATIONS
The prosocial effects elicited by repeated LSD administration are accompanied by alterations of hippocampal eCBome and kynurenine levels, and the composition of the gut microbiota. Modulation of the hippocampal eCBome and kynurenine pathway might represent a mechanism by which psychedelic compounds elicit prosocial effects and affect the gut microbiome.
Substances chimiques
Hallucinogens
0
Lysergic Acid Diethylamide
8NA5SWF92O
anandamide
UR5G69TJKH
Endocannabinoids
0
Kynurenine
343-65-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
721-739Subventions
Organisme : Canadian Institutes of Health Research (CIHR)
Organisme : Fonds de Recherche Santé du Québec (FRQS)
Organisme : Réseau Québécois sur le Suicide, les Troubles de l'Humeur et Troubles Associés (RQSHA)
Organisme : Quebec Autism Research Training Program (QART)
Organisme : NHMRC Senior Research Fellowship
Organisme : Matthew Flinders Professorial Fellowship
Organisme : Tri-Agency of the Canadian Federal Government
Informations de copyright
© 2022 British Pharmacological Society.
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