Effects of 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) on alcohol consumption in Long-Evans rats
Michael D. Berquist, William E Fantegrossi
Behavioural Pharmacology February 15, 2021 DOI: 10.1097/fbp.0000000000000628 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study (within-subject pharmacology in rats) Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Adult male Long–Evans rats given intermittent access to 20% ethanol |
| Intervention | Naltrexone |
| Dose | Naltrexone 1 mg/kg; DOI 0.1–1 mg/kg; both subcutaneous |
| Duration | 15 ethanol access sessions before testing; effects assessed for at least 24 h after treatment |
| Topics | Serotonin |
| Key findings | DOI dose-dependently reduced ethanol intake and preference for at least 24 hours, whereas naltrexone produced only a transient decrease in intake and an inconsistent effect on preference. Rats with the highest ethanol intake in the first 60 minutes of access showed the greatest reductions after DOI. The authors propose a 'baseline dependency' hypothesis in which heavier-drinking individuals may be most responsive to 5-HT2-targeting psychedelics. |
Abstract
Supplemental Digital Content is available in the text. The objectives of this study were to determine alcohol consumption after administration of (R)(-)-2,5-dimethoxy-4-iodoamphetamine (DOI) or naltrexone in Long–Evans rats, and to assess the effectiveness of these treatments based on individual differences in alcohol consumption. Adult male Long–Evans rats (N = 16) were given opportunities to orally self-administer a 20% (v/v) ethanol (EtOH) solution using an intermittent access, two-bottle (vs. tap water) choice procedure in their home cages. EtOH consumption and preference, total fluid consumption and food intake were measured. Last, we assessed the effects of naltrexone (1 mg/kg; subcutaneous) and (R)(-)-DOI (0.1–1 mg/kg; subcutaneous) on EtOH intake and preference using a quartile analysis. Rats showed stable EtOH (20%) intake and preference after 15 EtOH access sessions. Naltrexone produced a transient decrease in EtOH intake, but an inconsistent effect on EtOH preference, whereas DOI dose-dependently reduced EtOH intake and preference for at least 24 h. Subsequent quartile analyses revealed that rats with the highest EtOH intake during the first 60 min of access to EtOH showed greater reductions in EtOH intake and preference after DOI treatment. This is the first report to show that DOI-elicited reductions in EtOH intake and preference in rats depend on baseline EtOH intake, perhaps supporting a ‘baseline dependency’ hypothesis of effectiveness with phenethylamine psychedelics on EtOH consumption. If so, individuals with greater potential to develop severe AUDs may be particularly responsive to the positive motivational changes produced by treatment with psychedelics that target the 5-HT2 receptor family.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 17
- Psilocybin sex-dependently reduces alcohol consumption in C57BL/6J mice Frontiers in Pharmacology January 4, 2023
- Role of 5-HT2A receptors in the effects of ayahuasca on ethanol self-administration using a two-bottle choice paradigm in male mice Psychopharmacology March 7, 2022
- Animal Behavior in Psychedelic Research. Pharmacological Reviews October 1, 2022
- 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review. ACS Pharmacology & Translational Science June 14, 2024
- Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats Molecular Psychiatry October 21, 2024
and 12 more in the library
Cites 5
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
- Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials Journal of Psychopharmacology March 8, 2012
- LSD Administered as a Single Dose Reduces Alcohol Consumption in C57BL/6J Mice Frontiers in Pharmacology August 31, 2018
- Effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol consumption and place conditioning in male mice Psychopharmacology July 15, 2019