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Possible Involvement of Hallucinogenic Effects in the Aversive Effects Induced by Kappa-Opioid and 5-HT<sub>2A</sub> <sub>/2C</sub> Receptor Agonists in Mice.

Kato HiD, Ichimaru Y, Kurihara M, Sogawa K, Funada M, Suzuki T

Neuropsychopharmacology reportsDec 1, 2025License: open accessJapan1 citationsDOI: 10.1002/npr2.70075

Abstract

<h4>Aim</h4>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.<h4>Methods</h4>In the present study, we used the typical κ-opioid receptor agonist U50,488H and the typical 5-HT<sub>2A/2C</sub> 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.<h4>Results</h4>In the CPA test, both κ-opioid receptor and 5-HT<sub>2A/2C</sub> 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.<h4>Conclusion</h4>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.

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Psychedelics

Keywords

Conditioned Place AversionHallucinogenic Drugs5‐Ht2a/2c ReceptorKappa‐opioid

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