Effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol consumption and place conditioning in male mice.

Abstract:

RATIONALE:Approximately 20 million adults in the USA have an alcohol use disorder (AUD). There are clinical and preclinical data suggesting that psychedelics may have benefits for AUD. OBJECTIVE:To investigate the effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on the behavioral effects of ethanol. METHODS:The effects of DOI were examined using ethanol-induced place conditioning (1.8 g/kg ethanol) and 2-bottle choice ethanol drinking (20% v/v), using a dose of DOI (3 mg/kg) that produced the maximal response in the serotonin 2A (5-HT2A) receptor-dependent head-twitch assay. Interactions between DOI and ethanol (3 g/kg) were examined using the ethanol-induced loss of righting reflex procedure and blood-ethanol analysis. To examine additional mechanisms by which psychedelics may interact with ethanol, we determined whether DOI reverses ethanol-induced nitric oxide release in macrophages, a marker of inflammation. RESULTS:DOI significantly attenuated ethanol-induced place conditioning and ethanol drinking. DOI-induced suppression of alcohol drinking depended upon 5-HT2A receptors, was selective for alcohol over water, and was selective for high alcohol-preferring subjects. DOI had no apparent pharmacokinetic interactions with ethanol, and DOI reduced ethanol-induced nitric oxide release. CONCLUSIONS:Our findings demonstrate that DOI blocks ethanol place conditioning and selectively reduces voluntary ethanol consumption. This may be related to modulation of the effects of ethanol in the reward circuitry of the brain, ethanol-induced neuroinflammation, or a combination of both. Additional studies to elucidate the mechanisms through which psychedelics attenuate the effects of ethanol would inform the pathophysiology of AUD and potentially provide new treatment options.

journal_title

Psychopharmacology

authors

Oppong-Damoah A,Curry KE,Blough BE,Rice KC,Murnane KS

doi

10.1007/s00213-019-05328-7

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

3567-3578

issue

12

eissn

0033-3158

issn

1432-2072

pii

10.1007/s00213-019-05328-7

journal_volume

236

pub_type

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