Role of 5-HT Receptors in the Effects of Ayahuasca on Ethanol Self-administration Using a Two-bottle Choice Paradigm in Male Mice

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2022 Mar 7

PMID 35253069

Authors

Yasmim A Serra

Thaisa Barros-Santos

Alexia Anjos-Santos

Natali D Kisaki

Caio Jovita-Farias

Joao P C Leite

Maria C E Santana

Joao P S A Coimbra

Nailton M S de Jesus

Agnieszka Sulima

Paulo C R Barbosa

Elena L A Malpezzi-Marinho

Kenner C Rice

Alexandre J Oliveira-Lima

Lais F Berro

Eduardo A V Marinho

Affiliations

Soon will be listed here.

Abstract

Rationale: Ayahuasca has been proposed as a potential treatment of alcohol (ethanol) use disorder (AUD). The serotonin 5-HT receptor agonist N,N-dimethyltryptamine (DMT) is the main psychoactive component of ayahuasca, suggesting that its therapeutic effects may be mediated by 5-HT receptors.

Objectives: The aim of the present study was to investigate the effects of ayahuasca on the expression of ethanol self-administration using a two-bottle choice procedure and the role of 5-HT receptors in those effects.

Methods: Male mice had intermittent access to ethanol (10% v/v) in a two-bottle choice procedure for 30 days. Animals were then submitted to 3 treatment phases, each followed by ethanol re-exposure tests. During the treatment phase, every 3 days, animals received i.p. injections of either vehicle or the 5-HT receptor antagonist M100907 (M100, 1 mg/kg) followed by an i.g. (gavage) administration of vehicle or ayahuasca (100 mg/kg) and were exposed to the self-administration apparatus with no ethanol availability. During re-exposure tests, animals were submitted to the same conditions as during acquisition, with no treatments prior to those sessions.

Results: Treatment with ayahuasca blocked the expression of ethanol self-administration, decreasing ethanol intake and preference during re-exposure tests. Pretreatment with M100 blocked the effects of ayahuasca on ethanol drinking without significantly attenuating ethanol self-administration.

Conclusions: Treatment with ayahuasca during alcohol abstinence blocked the expression of alcohol self-administration in mice, and 5-HT receptor activation is critical for those effects to emerge. Our findings support a potential for ayahuasca and other 5-HT receptor agonists as adjunctive pharmacotherapies for the treatment of AUD.

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