Ethopharmacological evaluation of antidepressant-like effect of serotonergic psychedelics in C57BL/6J male mice
Rika Takaba, Daisuke Ibi, Keisuke Yoshida, Eri Hosomi, Ririna Kawase, Hiroko Kitagawa, Hirotaka Goto, Mizuki Achiwa, Kento Mizutani, Kyosuke Maede, Javier González-Maeso, Shinji Kitagaki, Masayuki Hiramatsu
Research Square (Research Square) July 7, 2023 preprint DOI: 10.21203/rs.3.rs-3138705/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Ethopharmacological study in mice |
|---|---|
| Population | Mice |
| Interventions | Psilocin DOI TCB-2 volinanserin |
| Duration | 24 h post-treatment for most tests; up to three weeks for psilocin's effect on FST |
| Topics | Anxiety LSD Psilocybin Serotonin |
| Keywords | Anxiolytic Pharmacology Antidepressant Tail suspension test Behavioural despair test Hallucinogen |
| Citations | 4 |
| Key points | 5-HT2A receptor activation is necessary for the antidepressant-like effects of serotonergic psychedelics in mice but not for their anxiolytic-like effects. |
Abstract
Abstract Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT 2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear. In this study, we ethopharmacologically analyzed the role of 5-HT2A in the occurrence of anxiolytic-and antidepressant-like effects of serotonergic psychedelics such as psilocin, an active metabolite of psilocybin, DOI, and TCB-2 in mice. Mice with acute intraperitoneal psychedelic treatment exhibited significantly shorter immobility times in the forced swimming test (FST) and tail-suspension test (TST) than vehicle-treated control mice 24 h post-treatment. These effects were eliminated by pretreatment with volinanserin, a 5-HT2A antagonist. Surprisingly, the decreasing immobility time in the FST in response to acute psilocin treatment was sustained for at least three weeks. In the novelty-suppressed feeding test (NSFT), the latency to feed, an indicator of anxiety-like behavior, was decreased by acute administration of psilocin; however, pretreatment with volinanserin did not diminish this effect. In contrast, DOI and TCB-2 did not affect the NSFT performance in mice. Furthermore, psilocin, DOI, and TCB-2 treatment did not affect the spontaneous locomotor activity or head-twitch response, a hallucination-like behavior in rodents. These results suggest that 5-HT2A contributes to the antidepressant effects of serotonergic psychedelics rather than an anxiolytic effects.
Comparable studies
Other preclinical and animal studies on LSD for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline Male mice exposed to chronic restraint stress | 2022 | Preclinical experimental study | |
| Repeated microdoses of LSD do not alter anxiety or boldness in zebrafish. Zebrafish (Danio rerio) | 2024 | Experimental study | |
| Psychedelics Improve the Mental Health of Rats Male Wistar-Kyoto (WKY) rats | 2019 | Controlled experiment | n = 42 |
| Addressing the Current Knowledge and Gaps in Research SurroundingLysergic Acid Diethylamide (LSD), Psilocybin, and Psilocin in RodentModels Rodent models | 2023 | Review |