Rapid antidepressant-like effect of non-hallucinogenic psychedelic analog lisuride, but not hallucinogenic psychedelic DOI, in lipopolysaccharide-treated mice.

Autor: Qu Y; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan., Chang L; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan., Ma L; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan., Wan X; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan., Hashimoto K; Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2023 Jan; Vol. 222, pp. 173500. Date of Electronic Publication: 2022 Dec 05.
DOI: 10.1016/j.pbb.2022.173500
Abstrakt: Classical psychedelics with 5-hydroxytryptamine-2A receptor (5-HT 2A R) agonism have rapid antidepressant actions in patients with depression. However, there is an ongoing debate over the role of 5-HT 2A R in the antidepressant-like actions of psychedelics. In this study, we compared the effects of DOI (2,5-dimethoxy-4-iodoamphetamine: a hallucinogenic psychedelic drug with potent 5-HT 2A R agonism), lisuride (non-hallucinogenic psychedelic analog with 5-HT 2A R and 5-HT 1A R agonisms), and the novel antidepressant (R)-ketamine on depression-like behavior and the decreased dendritic spine density in the brain of lipopolysaccharide (LPS)-treated mice. Saline (10 ml/kg), DOI (2.0 mg/kg), lisuride (1.0 mg/kg), or (R)-ketamine (10 mg/kg) was administered intraperitoneally to LPS (0.5 mg/kg, 23 h before)-treated mice. Both lisuride and (R)-ketamine significantly ameliorated the increased immobility time of forced swimming test, and the decreased dendritic spine density in the prelimbic region of medial prefrontal cortex, CA3 and dentate gyrus of hippocampus of LPS-treated mice. In contrast, DOI did not improve these changes produced after LPS administration. This study suggests that antidepressant-like effect of lisuride in LPS-treated mice is not associated with 5-HT 2A R-related psychedelic effects. It is, therefore, unlikely that 5-HT 2A R may play a major role in rapid-acting antidepressant actions of psychedelics although further detailed study is needed.
Competing Interests: Declaration of competing interest Dr. Hashimoto is the inventor of filed patent applications on “The use of R-ketamine in the treatment of psychiatric diseases”, “(S)-norketamine and salt thereof as pharmaceutical”, “R-ketamine and derivative thereof as prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder”, “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases”, and “R-ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder” by the Chiba University. Dr. Hashimoto has also received speakers' honoraria, consultant fee, or research support from Abbott, Boehringer-Ingelheim, Daiichi-Sankyo, Meiji Seika Pharma, Seikagaku Corporation, Dainippon-Sumitomo, Taisho, Otsuka, Murakami Farm and Perception Neuroscience. Other authors declare no conflict of interest.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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