Effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol consumption and place conditioning in male mice.
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. To investigate the effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on the behavioral effects of ethanol. The effects of DOI were examined using ethanol-induced place conditioning (1.8 gkg ethanol) and 2-bottle choice ethanol drinking (20% vv), using a dose of DOI (3 mgkg) that produced the maximal response in the serotonin 2A (5-HT DOI significantly attenuated ethanol-induced place conditioning and ethanol drinking. DOI-induced suppression of alcohol drinking depended upon 5-HT 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.