Possible Involvement of Hallucinogenic Effects in the Aversive Effects Induced by Kappa‐Opioid and 5‐ HT 2A / 2C Receptor Agonists in Mice
Hideaki Kato, Yoshimi Ichimaru, Masaaki Kurihara, Koushirou Sogawa, Masahiko Funada, Tsutomu Suzuki
Neuropsychopharmacology Reports November 23, 2025 DOI: 10.1002/npr2.70075 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | 1-(2 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) |
| Topics | Serotonin |
| Keywords | Hallucinogen 5-HT Receptor Agonist Pharmacology |
| Citations | 1 |
| Key findings | The hallucinogen-like receptor agonist DOI produced aversive effects and abnormal behavior in mice, suggesting these tests can evaluate hallucinogenic effects for drug regulation. |
Abstract
Aim: The regulation of new psychoactive and dangerous abused substances is very important for the prevention of drug abuse. A simple and effective evaluation method using laboratory animals is needed to regulate designated drugs with high accuracy and speed.
Methods: receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), which have a similar mechanism of action to hallucinogenic drugs, in a conditioned place aversion (CPA) test in mice. In addition, because hallucinogenic drugs can cause emotional abnormalities during hallucinations, we performed a marble-burying test in mice.
Results: receptor agonists produced significant aversive effects and abnormal behavior. These aversive effects and abnormal behavior were probably due in part to the hallucinogenic effects of these drugs.
Conclusion: Therefore, these tests using mice may be useful for evaluating hallucinogenic effects. We hope that these simple and rapid evaluation methods will be used to identify designated drugs.
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
Cites 7
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- d-Lysergic acid diethylamide, psilocybin, and other classic hallucinogens: Mechanism of action and potential therapeutic applications in mood disorders. Progress in Brain Research 2018
- Salvinorin A: a novel and highly selective kappa-opioid receptor agonist. Life Sciences October 15, 2004
- Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects Pharmaceuticals February 3, 2021
- Tolerance and cross-tolerance to head twitch behavior elicited by phenethylamine- and tryptamine-derived hallucinogens in mice. Journal of Pharmacology and Experimental Therapeutics December 1, 2014
and 2 more in the library