期刊
PSYCHOPHARMACOLOGY
卷 239, 期 6, 页码 1679-1687出版社
SPRINGER
DOI: 10.1007/s00213-022-06104-w
关键词
Ayahuasca; Ethanol; Serotonin; 5-HT2A; Self-administration; Mice
资金
- Universidade Estadual de Santa Cruz (UESC) [073.6769.2020.0017856-35]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Fundacao de Amparo a Pesquisa do Estado da Bahia (FAPESB)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- NIH Intramural Research Programs of the National Institute on Drug Abuse (NIDA)
- National Institute of Alcohol Abuse and Alcoholism (NIAAA)
The study found that ayahuasca treatment can block the expression of alcohol self-administration in mice, and the activation of 5-HT2A receptors is critical for these effects. This suggests the potential of ayahuasca and other 5-HT2A receptor agonists as adjunctive pharmacotherapies for the treatment of AUD.
Rationale Ayahuasca has been proposed as a potential treatment of alcohol (ethanol) use disorder (AUD). The serotonin 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT) is the main psychoactive component of ayahuasca, suggesting that its therapeutic effects may be mediated by 5-HT2A 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-HT2A 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-HT2A 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-HT2A receptor activation is critical for those effects to emerge. Our findings support a potential for ayahuasca and other 5-HT2A receptor agonists as adjunctive pharmacotherapies for the treatment of AUD.
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